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2023
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Clifford, Jarrett, Cheng, Cheng, Seldin, Morand, Lee, Chen, Baldan, de Aguiar Vallim, Tarling. (2023). RNF130 Regulates LDLR Availability and Plasma LDL Cholesterol Levels. Circ Res, 132(7), pp849-863.
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2023
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Xiao, Kennelly, Ferrari, Clifford, Whang, Gao, Qian, Sandhu, Jarrett, Brearley-Sholto, Nguyen, Nagari, Lee, Zhang, Weston, Young, Bensinger, Villanueva, de Aguiar Vallim, Tontonoz. (2023). Hepatic nonvesicular cholesterol transport is critical for systemic lipid homeostasis. Nat Metab, 5(1), pp165-181.
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2022
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Ilacqua, Anastasia, Aloshyn, Ghandehari-Alavijeh, Peluso, Brearley-Sholto, Pellegrini, Raimondi, de Aguiar Vallim, Pellegrini. (2022). Expression of Synj2bp in mouse liver regulates the extent of wrappER-mitochondria contact to maintain hepatic lipid homeostasis. Biol Direct, 17(1), pp37.
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2022
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Moore, Cheng, Wolf, Ngo, Segawa, Zhu, Strumwasser, Cao, Clifford, Ma, Scumpia, Shirihai, Vallim, Laakso, Lusis, Hevener, Zhou. (2022). Parkin regulates adiposity by coordinating mitophagy with mitochondrial biogenesis in white adipocytes. Nat Commun, 13(1), pp6661.
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2022
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De Giorgi, Jarrett, de Aguiar Vallim, Lagor. (2022). In Vivo Gene Editing in Lipid and Atherosclerosis Research. Methods Mol Biol, 2419, pp613-713.
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2022
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O'Callaghan, Helly, Tarling, Keane, McCarthy. (2022). Methionine supplementation: potential for improving alveolar macrophage function through reverse cholesterol transport? Eur Respir J, 59(5), pp2102594.
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2022
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Doerfler, Han, Jarrett, Tang, Jain, Saltzman, De Giorgi, Chuecos, Hurley, Li, Morand, Ayala, Goodlett, Malovannaya, Martin, de Aguiar Vallim, Shroyer, Lagor. (2022). Intestinal Deletion of 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Promotes Expansion of the Resident Stem Cell Compartment. Arterioscler Thromb Vasc Biol, 42(4), pp381-394.
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2022
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Yildirim, Baboo, Hamid, Dogan, Tufanli, Robichaud, Emerton, Diedrich, Vatandaslar, Nikolos, Gu, Iwawaki, Tarling, Ouimet, Nelson, Yates, Walter, Erbay. (2022). Intercepting IRE1 kinase-FMRP signaling prevents atherosclerosis progression. EMBO Mol Med, 14(4), pp15344.
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2022
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Ilacqua, Anastasia, Raimondi, Lemieux, de Aguiar Vallim, Toth, Koonin, Pellegrini. (2022). A three-organelle complex made by wrappER contacts with peroxisomes and mitochondria repsonds to liver lipid flux changes. J Cell Sci, 135(5), pp259091.
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2022
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Mukherjee, Chattopadhyay, Grijalva, Dorreh, Lagishetty, Jacobs, Clifford, Vallim, Mack, Navab, Reddy, Fogleman. (2022). Oxidized phospholipids cause changes in jejunum mucus that induce dysbiosis and systemic inflammation. J Lipid Res, 63(1), pp100153.
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2021
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Ataya, Knight, Carey, Lee, Tarling, Wang. (2021). The Role of GM-CSF Autoantibodies in Infection and Autoimmune Pulmonary Alveolar Proteinosis: A Concise Review. Front Immunol, 12, pp752856.
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2021
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Clifford, Sedgeman, Williams, Morand, Cheng, Jarrett, Chan, Brearely-Sholto, Wahlström, Ashby, Barshop, Wolhschlegel, Calkin, Liu, Thorell, Meikle, Drew, Mack, Marschall, Tarling, Edwards, de Aguiar Vallim. (2021). FXR activation protects against NAFLD via bile acid-dependent reductions in lipid absorption. Cell Metab, 33(8), pp1671-1684.
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2021
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Zhuang, Calkin, Lau, Kiriazis, Donner, Liu, Bond, Moody, Gould, Colgan, Carmona, Inouye, de Aguiar Vallim, Tarling, Quaife-Ryan, Hudson, Porello, Gregorovic, Gao, Du, McMullen, Drew. (2021). Loss of the long non-coding RNA OIP5-AS1 exacerbates heart failure in a sex-specific manner. iScience, 24(6), pp102537.
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2021
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de Aguiar Vallim, Tarling. (2021). mInd the gAP. Circ Res, 128(11), pp1660-1662.
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2021
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Anastasia, Ilacqua, Raimondi, Lemieux, Ghandehari-Alavijeh, Faure, Mekhedov, Williams, Caicci, Valle, Giacomello, Quiroga, Lehner, Miksis, Toth, de Aguiar Vallim, Koonin, Scorrano, Pellegrini. (2021). Mitochondria-rough-ER contacts in the liver regulate systemic lipid homeostasis. Cell Rep, 34(11), pp108873.
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2021
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von Sheidt, Zhao, de Aguiar Vallim, Che, Wierer, Seldin, Franzén, Kurt, Pang, Bongiovanni, Yamamoto, Edwards, Ruusalepp, Kovacic, Mann, Björkegren, Lusis, Yang, Schunkert. (2021). Transcription Factor MAFF (MAF Basic Leucine Zipper Transcription Factor F) Regulates an Atherosclerosis Relevant Network Connecting Inflammation and Cholesterol Metabolism. Circulation, 143(18), pp1809-1823.
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2021
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Bond, King, Henstridge, Tran, Moody, Yang, Liu, Mellett, Nath Inouye, Tarling, de Aguiar Vallim, Meikle, Calkin, Drew. (2021). Deletion of Trim28 in committed adipocytes promotes obesity but preserves glucose tolerance. Nat Commun, 12(74).
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2020
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Clifford, Jarrett, Cheng, Cheng, Seldin, Morand, Lee, Baldan, de Aguiar Vallim, Tarling. (2020). GOLIATH regulates LDLR availbility and plasma LDL cholesterol levels. bioRxiv.
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2020
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Zhou, Chi, Lee, Hsieh, Mkrtchyan, Feng, He, York, Bui, Kronenberger, Ferrari, Xiao, Daly, Tarling, Damoiseaux, Scumpia, Smale, Williams, Tontonoz, Bensinger. (2020). Interferon-mediated reprogramming of membrane cholesterol to evade bacterial toxins. Nat Immunol, 21(7), pp746-755.
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2020
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Pradas-Juni, Hansmeier, Link, Schmidt, Larsen, Klemm, Meola, Topei, Loureiro, Dhaoudai, Kiefer, Schwarzer, Khani, Oliverio, Awazawa, Frommolt, Heeren, Scheja, Heine, Dietrich, Buning, Yang, Cao, Jesus, Kulkarni, Zevnik, Troder, Knippschild, Edwards, Lee, Yamamoto, Ulitsky, Fernandez-Rebollo, Vallim, Kornfeld (2020). A MAFG-lncRNA axis links systemic nutrient abundance to hepatic glucose metabolism. Nat Commun, 11(1), pp644.
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2020
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Cheng, Cheng, Clifford, Wu, Hedin, Maegdefessel, Pamir, Sallam, Tarling, de Aguiar Vallim. (2020). MicroRNA-144 Silencing Protects Against Atherosclerosis in Male, but Not Female Mice. Arterioscler Thromb Vasc Biol, 40(2), pp412-420.
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2019
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Parker, Calkin, Seldin, Keating, Tarling, Yang, Moody, Liu, Zerenturk, Needham, Miller, Clifford, Morand, Watt, Meex, Peng, Lee, Jayawardana, Pan, Mellett, Weir, Lazarus, Lusis, Miekle, James, Aguiar Vallim, Drew. (2019). An integrative systems genetics analysis of mammalian lipid metabolism. Nature, 567(7747), pp187-193.
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2019
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Pamir, Pan, Plubell, Hutchins, Tang, Wimberger, Irwin, Aguiar Vallim, Heinecke, Lusis (2019). Genetic control of the mouse HDL proteome defines HDL traits, function, and heterogeneity. J Lipid Res, 60(3), pp. 594.
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2018
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Sullivan, Mullen, Schmid, Flores, Momcilovic, Sharpley, Jelinek, Whiteley, Maxwell, Wilde, Banerjee, Coller, Shackelford, Braas, Ayer, Aguiar Vallim, Lowry, Christofk (2018). Extracelular Matrix Remodeling Regulates Glucose Metabolism through TXNIP Destabilization. Cell, 175(1), pp.117.
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2018
|
McCarthy, Lee, Bridges, Sallese, Suzuki, Woods, Bartholmai, Wang, Chalk, Carey, Arumugam, Shima, Tarling, Trapnell (2018). Statin as a novel pharmacotherapy of pulmonary alveolar proteinosis. Nat Commun, 9(1), pp. 3127.
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2018
|
Tumurkhuu, Dagvadorj, Porritt, Crother, Shimada, Tarling, Erbay, Arditi, Chen (2018). Chlamydia pneumoniae Hijacks a Host Autoregulatory IL-1ß Loop to Drive Foam Cell Formation and Accelerate Atherosclerosis. Cell Metab, Jun 18 pii: S1550-4131(18)30380-2.
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2018
|
Lee, Ong, Vergnes, Aguiar Vallim, Nolan, Cantor, Walters, Reue (2018). Diet1, bile acid diarrhea, and FGF15/19: mouse model and human genetic variants. J Lipid Res, 59(3), pp.429.
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2017
|
Mack, Mosquerio, Archer, Jones, Sunshine, Faas, Briot, Aragon, Su, Romay, McDonald, Kuo, Lizama, Lane, Zovein, Fang, Tarling, Aguiar Vallim, Navab, Fogelman, Bouchard, Iruela-Arispe (2017). NOTCH1 is a mechanosensor in adult arteries. Nat Commun, 8(1), pp.1620.
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2017
|
Zhang, Rajbhandari, Priest, Sandhu, Wu, Temel, Castrillo, Aguiar Vallim, Sallam, Tontonoz (2017). Inhibition of cholesterol biosynthesis through RNF145-dependent ubiquitination of SCAP.
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2017
|
Aguiar Vallim, Lee, Merriott, Goulbourne, Cheng, Cheng, Gonen, Allen, Palladino, Ford, Wang, Baldán, Tarling (2017). ABCG1 regulates pulmonary surfactant metabolism in mice and men. J Lipid Res, 58(5), pp. 941-954. (bib)
x
@article{Aguiar-Vallim:2017aa,
bdsk-url-1 = { http://dx.doi.org/10.1194/jlr.M075101 },
year = { 2017 },
volume = { 58 },
title = { ABCG1 regulates pulmonary surfactant metabolism in mice and men },
pst = { ppublish },
pmid = { 28264879 },
pmc = { PMC5408613 },
pages = { 941-954 },
number = { 5 },
month = { May },
keywords = { ATP binding cassette transporter G1; cholesterol; lung; phospholipid; pulmonary alveolar proteinosis },
journal-full = { Journal of lipid research },
journal = { J Lipid Res },
doi = { 10.1194/jlr.M075101 },
date-modified = { 2017-10-16 01:50:16 +0000 },
date-added = { 2017-10-16 01:50:16 +0000 },
author = { Aguiar Vallim and Lee and Merriott and Goulbourne and Cheng and Cheng and Gonen and Allen and Palladino and Ford and Wang and Bald{\'a}n and Tarling },
abstract = { Idiopathic pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by accumulation of surfactant. Surfactant synthesis and secretion are restricted to epithelial type 2 (T2) pneumocytes (also called T2 cells). Clearance of surfactant is dependent upon T2 cells and macrophages. ABCG1 is highly expressed in both T2 cells and macrophages. ABCG1-deficient mice accumulate surfactant, lamellar body-loaded T2 cells, lipid-loaded macrophages, B-1 lymphocytes, and immunoglobulins, clearly demonstrating that ABCG1 has a critical role in pulmonary homeostasis. We identify a variant in the ABCG1 promoter in patients with PAP that results in impaired activation of ABCG1 by the liver X receptor α, suggesting that ABCG1 basal expression and/or induction in response to sterol/lipid loading is essential for normal lung function. We generated mice lacking ABCG1 specifically in either T2 cells or macrophages to determine the relative contribution of these cell types on surfactant lipid homeostasis. These results establish a critical role for T2 cell ABCG1 in controlling surfactant and overall lipid homeostasis in the lung and in the pathogenesis of human lung disease. },
}
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|
2017
|
Rong, Wang, Palladino, Aguiar Vallim, Ford, Tontonoz (2017). ER phospholipid composition modulates lipogenesis during feeding and in obesity. J Clin Invest, 127(10), pp. 3640-3651. (bib)
x
@article{Rong:2017aa,
bdsk-url-1 = { http://dx.doi.org/10.1172/JCI93616 },
year = { 2017 },
volume = { 127 },
title = { ER phospholipid composition modulates lipogenesis during feeding and in obesity },
pst = { ppublish },
pmid = { 28846071 },
pmc = { PMC5617651 },
pages = { 3640-3651 },
number = { 10 },
month = { Oct },
journal-full = { The Journal of clinical investigation },
journal = { J Clin Invest },
doi = { 10.1172/JCI93616 },
date-modified = { 2017-10-16 01:50:30 +0000 },
date-added = { 2017-10-16 01:50:30 +0000 },
author = { Rong and Wang and Palladino and Aguiar Vallim and Ford and Tontonoz },
abstract = { Sterol regulatory element-binding protein 1c (SREBP-1c) is a central regulator of lipogenesis whose activity is controlled by proteolytic cleavage. The metabolic factors that affect its processing are incompletely understood. Here, we show that dynamic changes in the acyl chain composition of ER phospholipids affect SREBP-1c maturation in physiology and disease. The abundance of polyunsaturated phosphatidylcholine in liver ER is selectively increased in response to feeding and in the setting of obesity-linked insulin resistance. Exogenous delivery of polyunsaturated phosphatidylcholine to ER accelerated SREBP-1c processing through a mechanism that required an intact SREBP cleavage-activating protein (SCAP) pathway. Furthermore, induction of the phospholipid-remodeling enzyme LPCAT3 in response to liver X receptor (LXR) activation promoted SREBP-1c processing by driving the incorporation of polyunsaturated fatty acids into ER. Conversely, LPCAT3 deficiency increased membrane saturation, reduced nuclear SREBP-1c abundance, and blunted the lipogenic response to feeding, LXR agonist treatment, or obesity-linked insulin resistance. Desaturation of the ER membrane may serve as an auxiliary signal of the fed state that promotes lipid synthesis in response to nutrient availability. },
}
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|
2017
|
Tarling, Clifford, Cheng, Morand, Cheng, Lester, Sallam, Turner, Aguiar Vallim (2017). RNA-binding protein ZFP36L1 maintains posttranscriptional regulation of bile acid metabolism. J Clin Invest, 127(10), pp. 3741-3754. (bib)
x
@article{Tarling:2017aa,
bdsk-url-1 = { http://dx.doi.org/10.1172/JCI94029 },
year = { 2017 },
volume = { 127 },
title = { RNA-binding protein ZFP36L1 maintains posttranscriptional regulation of bile acid metabolism },
pst = { ppublish },
pmid = { 28891815 },
pmc = { PMC5617661 },
pages = { 3741-3754 },
number = { 10 },
month = { Oct },
journal-full = { The Journal of clinical investigation },
journal = { J Clin Invest },
doi = { 10.1172/JCI94029 },
date-modified = { 2017-10-16 01:50:52 +0000 },
date-added = { 2017-10-16 01:50:52 +0000 },
author = { Tarling and Clifford and Cheng and Morand and Cheng and Lester and Sallam and Turner and Aguiar Vallim },
abstract = { Bile acids function not only as detergents that facilitate lipid absorption but also as signaling molecules that activate the nuclear receptor farnesoid X receptor (FXR). FXR agonists are currently being evaluated as therapeutic agents for a number of hepatic diseases due to their lipid-lowering and antiinflammatory properties. FXR is also essential for maintaining bile acid homeostasis and prevents the accumulation of bile acids. Elevated bile acids activate FXR, which in turn switches off bile acid synthesis by reducing the mRNA levels of bile acid synthesis genes, including cholesterol 7α-hydroxylase (Cyp7a1). Here, we show that FXR activation triggers a rapid posttranscriptional mechanism to degrade Cyp7a1 mRNA. We identified the RNA-binding protein Zfp36l1 as an FXR target gene and determined that gain and loss of function of ZFP36L1 reciprocally regulate Cyp7a1 mRNA and bile acid levels in vivo. Moreover, we found that mice lacking hepatic ZFP36L1 were protected from diet-induced obesity and steatosis. The reduced adiposity and antisteatotic effects observed in ZFP36L1-deficient mice were accompanied by impaired lipid absorption that was consistent with altered bile acid metabolism. Thus, the ZFP36L1-dependent regulation of bile acid metabolism is an important metabolic contributor to obesity and hepatosteatosis. },
}
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|
2016
|
Ribas, Drew, Zhou, Phun, Kalajian, Soleymani, Daraei, Widjaja, Wanagat, Aguiar Vallim, Fluitt, Bensinger, Le, Radu, Whitelegge, Beaven, Tontonoz, Lusis, Parks, Vergnes, Reue, Singh, Bopassa, Toro, Stefani, Watt, Schenk, Akerstrom, Kelly, Pedersen, Hewitt, Korach, Hevener (2016). Skeletal muscle action of estrogen receptor α is critical for the maintenance of mitochondrial function and metabolic homeostasis in females. Sci Transl Med, 8(334), pp. 334ra54. (bib)
x
@article{Ribas:2016aa,
bdsk-url-1 = { http://dx.doi.org/10.1126/scitranslmed.aad3815 },
year = { 2016 },
volume = { 8 },
title = { Skeletal muscle action of estrogen receptor α is critical for the maintenance of mitochondrial function and metabolic homeostasis in females },
pst = { ppublish },
pmid = { 27075628 },
pmc = { PMC4934679 },
pages = { 334ra54 },
number = { 334 },
month = { Apr },
mesh = { Animals; Autophagy; DNA Replication; DNA, Mitochondrial; Dynamins; Estrogen Receptor alpha; Female; Gene Deletion; Glucose; Homeostasis; Humans; Insulin; Intracellular Signaling Peptides and Proteins; Lipid Metabolism; Mice; Mice, Knockout; Mitochondria, Muscle; Mitochondrial Dynamics; Muscle Proteins; Muscle, Skeletal; Organ Specificity; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species; Signal Transduction },
journal-full = { Science translational medicine },
journal = { Sci Transl Med },
doi = { 10.1126/scitranslmed.aad3815 },
date-modified = { 2017-10-16 01:49:08 +0000 },
date-added = { 2017-10-16 01:49:08 +0000 },
author = { Ribas and Drew and Zhou and Phun and Kalajian and Soleymani and Daraei and Widjaja and Wanagat and Aguiar Vallim and Fluitt and Bensinger and Le and Radu and Whitelegge and Beaven and Tontonoz and Lusis and Parks and Vergnes and Reue and Singh and Bopassa and Toro and Stefani and Watt and Schenk and Akerstrom and Kelly and Pedersen and Hewitt and Korach and Hevener },
abstract = { Impaired estrogen receptor α (ERα) action promotes obesity and metabolic dysfunction in humans and mice; however, the mechanisms underlying these phenotypes remain unknown. Considering that skeletal muscle is a primary tissue responsible for glucose disposal and oxidative metabolism, we established that reduced ERα expression in muscle is associated with glucose intolerance and adiposity in women and female mice. To test this relationship, we generated muscle-specific ERα knockout (MERKO) mice. Impaired glucose homeostasis and increased adiposity were paralleled by diminished muscle oxidative metabolism and bioactive lipid accumulation in MERKO mice. Aberrant mitochondrial morphology, overproduction of reactive oxygen species, and impairment in basal and stress-induced mitochondrial fission dynamics, driven by imbalanced protein kinase A-regulator of calcineurin 1-calcineurin signaling through dynamin-related protein 1, tracked with reduced oxidative metabolism in MERKO muscle. Although muscle mitochondrial DNA (mtDNA) abundance was similar between the genotypes, ERα deficiency diminished mtDNA turnover by a balanced reduction in mtDNA replication and degradation. Our findings indicate the retention of dysfunctional mitochondria in MERKO muscle and implicate ERα in the preservation of mitochondrial health and insulin sensitivity as a defense against metabolic disease in women. },
}
|
|
2016
|
Zhang, Aguiar Vallim, Martel, Early Career Committee (2016). Translational and Therapeutic Approaches to the Understanding and Treatment of Dyslipidemia. Arterioscler Thromb Vasc Biol, 36(7), pp. e56-61. (bib)
x
@article{Zhang:2016aa,
bdsk-url-1 = { http://dx.doi.org/10.1161/ATVBAHA.116.307808 },
year = { 2016 },
volume = { 36 },
title = { Translational and Therapeutic Approaches to the Understanding and Treatment of Dyslipidemia },
pst = { ppublish },
pmid = { 27335468 },
pmc = { PMC4920133 },
pages = { e56-61 },
number = { 7 },
month = { Jul },
keywords = { PCSK9 protein; cardiovascular diseases; cholesterol; cholesterol, HDL; lipids; lipoproteins },
journal-full = { Arteriosclerosis, thrombosis, and vascular biology },
journal = { Arterioscler Thromb Vasc Biol },
doi = { 10.1161/ATVBAHA.116.307808 },
date-modified = { 2017-10-16 01:49:22 +0000 },
date-added = { 2017-10-16 01:49:22 +0000 },
author = { Zhang and Aguiar Vallim and Martel and {Early Career Committee} },
}
|
|
2016
|
Tarling, Edwards (2016). Intracellular Localization of Endogenous Mouse ABCG1 Is Mimicked by Both ABCG1-L550 and ABCG1-P550-Brief Report. Arterioscler Thromb Vasc Biol, 36(7), pp. 1323-7. (bib)
x
@article{Tarling:2016aa,
bdsk-url-1 = { http://dx.doi.org/10.1161/ATVBAHA.116.307414 },
year = { 2016 },
volume = { 36 },
title = { Intracellular Localization of Endogenous Mouse ABCG1 Is Mimicked by Both ABCG1-L550 and ABCG1-P550-Brief Report },
pst = { ppublish },
pmid = { 27230131 },
pmc = { PMC4919203 },
pages = { 1323-7 },
number = { 7 },
month = { Jul },
mesh = { ATP Binding Cassette Transporter, Sub-Family G, Member 1; Amino Acid Sequence; Animals; Biological Transport; CHO Cells; COS Cells; Cercopithecus aethiops; Cholesterol; Cholesterol, HDL; Cricetulus; Endosomes; Genotype; HEK293 Cells; Humans; Leucine; Liver X Receptors; Macrophages, Peritoneal; Mice; Mice, Inbred C57BL; Mice, Knockout; Phenotype; Primary Cell Culture; Proline; Sterol Regulatory Element Binding Protein 2; Transfection },
keywords = { ABC transporter; cholesterol homeostasis; lipids },
journal-full = { Arteriosclerosis, thrombosis, and vascular biology },
journal = { Arterioscler Thromb Vasc Biol },
doi = { 10.1161/ATVBAHA.116.307414 },
date-modified = { 2017-10-16 01:49:36 +0000 },
date-added = { 2017-10-16 01:49:36 +0000 },
author = { Tarling and Edwards },
abstract = { OBJECTIVE: In a recent article in Arteriosclerosis, Thrombosis, and Vascular Biology, it was reported that ATP-binding cassette transporter G1 (ABCG1) containing leucine at position 550 (ABCG1-L550) was localized to the plasma membrane, whereas ABCG1-P550 (proline at position 550) was intracellular. Because the published data on the subcellular localization of ABCG1 are controversial, we performed additional experiments to determine the importance of leucine or proline at amino acid 550.
APPROACH AND RESULTS: We transfected multiple cell lines (CHO-K1, Cos-7, and HEK293 [human embryonic kidney]) with untagged or FLAG-tagged ABCG1 containing either leucine or proline at position 550. Immunofluorescence studies demonstrated that in all cases, ABCG1 localized to intracellular endosomal vesicles. We also show that both ABCG1-L550 and ABCG1-P550 are equally active in both promoting the efflux of cellular cholesterol to exogenous high-density lipoprotein and in inducing the activity of sterol regulatory element-binding protein-2, presumably as a result of redistributing intracellular sterols away from the endoplasmic reticulum. Importantly, we treated nontransfected primary peritoneal macrophages with a liver X receptor agonist and demonstrate, using immunofluorescence, that although endogenous ABCG1 localizes to intracellular endosomes, none was detectable at the cell surface/plasma membrane.
CONCLUSIONS: ABCG1, irrespective of either a leucine or proline at position 550, is an intracellular protein that localizes to vesicles of the endosomal pathway where it functions to mobilize sterols away from the endoplasmic reticulum and out of the cell. },
}
|
|
2016
|
Tarling, Ryan, Austin, Kugler, Salter, Langley-Evans (2016). Maternal high-fat feeding in pregnancy programs atherosclerotic lesion size in the ApoE*3 Leiden mouse. J Dev Orig Health Dis, pp. 1-8. (bib)
x
@article{Tarling:2016ab,
bdsk-url-1 = { http://dx.doi.org/10.1017/S2040174416000027 },
year = { 2016 },
title = { Maternal high-fat feeding in pregnancy programs atherosclerotic lesion size in the ApoE*3 Leiden mouse },
pst = { aheadofprint },
pmid = { 26829884 },
pages = { 1-8 },
month = { Feb },
keywords = { animal; developmental stage; fetus; small animals },
journal-full = { Journal of developmental origins of health and disease },
journal = { J Dev Orig Health Dis },
doi = { 10.1017/S2040174416000027 },
date-modified = { 2017-10-16 01:49:56 +0000 },
date-added = { 2017-10-16 01:49:56 +0000 },
author = { Tarling and Ryan and Austin and Kugler and Salter and Langley-Evans },
abstract = { Periods of rapid growth seen during the early stages of fetal development, including cell proliferation and differentiation, are greatly influenced by the maternal environment. We demonstrate here that over-nutrition, specifically exposure to a high-fat diet in utero, programed the extent of atherosclerosis in the offspring of ApoE*3 Leiden transgenic mice. Pregnant ApoE*3 Leiden mice were fed either a control chow diet (2.8% fat, n=12) or a high-fat, moderate-cholesterol diet (MHF, 19.4% fat, n=12). Dams were fed the chow diet during the suckling period. At 28 days postnatal age wild type and ApoE*3 Leiden offspring from chow or MHF-fed mothers were fed either a control chow diet (n=37) or a diet rich in cocoa butter (15%) and cholesterol (0.25%), for 14 weeks to induce atherosclerosis (n=36). Offspring from MHF-fed mothers had 1.9-fold larger atherosclerotic lesions (P<0.001). There was no direct effect of prenatal diet on plasma triglycerides or cholesterol; however, transgenic ApoE*3 Leiden offspring displayed raised cholesterol when on an atherogenic diet compared with wild-type controls (P=0.031). Lesion size was correlated with plasma lipid parameters after adjustment for genotype, maternal diet and postnatal diet (R 2=0.563, P<0.001). ApoE*3 Leiden mothers fed a MHF diet developed hypercholesterolemia (plasma cholesterol two-fold higher than in chow-fed mothers, P=0.011). The data strongly suggest that maternal hypercholesterolemia programs later susceptibility to atherosclerosis. This is consistent with previous observations in humans and animal models. },
}
|
|
2015
|
York, Williams, Argus, Zhou, Brar, Vergnes, Gray, Zhen, Wu, Yamada, Cunningham, Tarling, Wilks, Casero, Gray, Yu, Wang, Brooks, Sun, Kitchen, Wu, Reue, Stetson, Bensinger (2015). Limiting Cholesterol Biosynthetic Flux Spontaneously Engages Type I IFN Signaling. Cell, 163(7), pp. 1716-29. (bib)
x
@article{York:2015aa,
bdsk-url-1 = { http://dx.doi.org/10.1016/j.cell.2015.11.045 },
year = { 2015 },
volume = { 163 },
title = { Limiting Cholesterol Biosynthetic Flux Spontaneously Engages Type I IFN Signaling },
pst = { ppublish },
pmid = { 26686653 },
pmc = { PMC4783382 },
pages = { 1716-29 },
number = { 7 },
month = { Dec },
mesh = { Animals; Cell Line, Tumor; Cholesterol; Humans; Immunity, Innate; Interferon beta-1b; Interferon-gamma; Membrane Proteins; Mevalonic Acid; Mice; Mice, Inbred C57BL; Signal Transduction; Sterol Regulatory Element Binding Protein 1; Sterol Regulatory Element Binding Protein 2 },
journal-full = { Cell },
journal = { Cell },
doi = { 10.1016/j.cell.2015.11.045 },
date-modified = { 2017-10-16 01:47:26 +0000 },
date-added = { 2017-10-16 01:47:26 +0000 },
author = { York and Williams and Argus and Zhou and Brar and Vergnes and Gray and Zhen and Wu and Yamada and Cunningham and Tarling and Wilks and Casero and Gray and Yu and Wang and Brooks and Sun and Kitchen and Wu and Reue and Stetson and Bensinger },
abstract = { Cellular lipid requirements are achieved through a combination of biosynthesis and import programs. Using isotope tracer analysis, we show that type I interferon (IFN) signaling shifts the balance of these programs by decreasing synthesis and increasing import of cholesterol and long chain fatty acids. Genetically enforcing this metabolic shift in macrophages is sufficient to render mice resistant to viral challenge, demonstrating the importance of reprogramming the balance of these two metabolic pathways in vivo. Unexpectedly, mechanistic studies reveal that limiting flux through the cholesterol biosynthetic pathway spontaneously engages a type I IFN response in a STING-dependent manner. The upregulation of type I IFNs was traced to a decrease in the pool size of synthesized cholesterol and could be inhibited by replenishing cells with free cholesterol. Taken together, these studies delineate a metabolic-inflammatory circuit that links perturbations in cholesterol biosynthesis with activation of innate immunity. },
}
|
|
2015
|
Wei, Tarling, McMillen, Tang, LeBoeuf (2015). ABCG1 regulates mouse adipose tissue macrophage cholesterol levels and ratio of M1 to M2 cells in obesity and caloric restriction. J Lipid Res, 56(12), pp. 2337-47. (bib)
x
@article{Wei:2015aa,
bdsk-url-1 = { http://dx.doi.org/10.1194/jlr.M063354 },
year = { 2015 },
volume = { 56 },
title = { ABCG1 regulates mouse adipose tissue macrophage cholesterol levels and ratio of M1 to M2 cells in obesity and caloric restriction },
pst = { ppublish },
pmid = { 26489644 },
pmc = { PMC4655989 },
pages = { 2337-47 },
number = { 12 },
month = { Dec },
mesh = { ATP Binding Cassette Transporter, Sub-Family G, Member 1; ATP-Binding Cassette Transporters; Adipose Tissue; Animals; Caloric Restriction; Cholesterol; Lipoproteins; Macrophages; Male; Mice; Mice, Inbred C57BL; Obesity },
keywords = { ATP binding cassette transporter A1; ATP binding cassette transporter G1; acyl-CoA:cholesterol acyltransferase; diabetes; fatty acid; gallstones; lipids; mice; nutrition; sterols },
journal-full = { Journal of lipid research },
journal = { J Lipid Res },
doi = { 10.1194/jlr.M063354 },
date-modified = { 2017-10-16 01:47:51 +0000 },
date-added = { 2017-10-16 01:47:51 +0000 },
author = { Wei and Tarling and McMillen and Tang and LeBoeuf },
abstract = { In addition to triacylglycerols, adipocytes contain a large reserve of unesterified cholesterol. During adipocyte lipolysis and cell death seen during severe obesity and weight loss, free fatty acids and cholesterol become available for uptake and processing by adipose tissue macrophages (ATMs). We hypothesize that ATMs become cholesterol enriched and participate in cholesterol clearance from adipose tissue. We previously showed that ABCG1 is robustly upregulated in ATMs taken from obese mice and further enhanced by caloric restriction. Here, we found that ATMs taken from obese and calorie-restricted mice derived from transplantation of WT or Abcg1-deficient bone marrow are cholesterol enriched. ABCG1 levels regulate the ratio of classically activated (M1) to alternatively activated (M2) ATMs and their cellular cholesterol content. Using WT and Abcg1(-/-) cultured macrophages, we found that Abcg1 is most highly expressed by M2 macrophages and that ABCG1 deficiency is sufficient to retard macrophage chemotaxis. However, changes in myeloid expression of Abcg1 did not protect mice from obesity or impaired glucose homeostasis. Overall, ABCG1 modulates ATM cholesterol content in obesity and weight loss regimes leading to an alteration in M1 to M2 ratio that we suggest is due to the extent of macrophage egress from adipose tissue. },
}
|
|
2015
|
Ito, Hong, Rong, Zhu, Tarling, Hedde, Gratton, Parks, Tontonoz (2015). LXRs link metabolism to inflammation through Abca1-dependent regulation of membrane composition and TLR signaling. Elife, 4, pp. e08009. (bib)
x
@article{Ito:2015aa,
bdsk-url-1 = { http://dx.doi.org/10.7554/eLife.08009 },
year = { 2015 },
volume = { 4 },
title = { LXRs link metabolism to inflammation through Abca1-dependent regulation of membrane composition and TLR signaling },
pst = { epublish },
pmid = { 26173179 },
pmc = { PMC4517437 },
pages = { e08009 },
month = { Jul },
mesh = { ATP Binding Cassette Transporter 1; Animals; Cell Membrane; Cells, Cultured; Chromatin Immunoprecipitation; Gene Expression Profiling; Inflammation; Liver X Receptors; Mice; Orphan Nuclear Receptors; Signal Transduction; Toll-Like Receptors },
keywords = { LXR; Toll-like receptor; cell biology; chromosomes; genes; lipid metabolism; mouse; nuclear receptor },
journal-full = { eLife },
journal = { Elife },
doi = { 10.7554/eLife.08009 },
date-modified = { 2017-10-16 01:48:20 +0000 },
date-added = { 2017-10-16 01:48:20 +0000 },
author = { Ito and Hong and Rong and Zhu and Tarling and Hedde and Gratton and Parks and Tontonoz },
abstract = { The liver X receptors (LXRs) are transcriptional regulators of lipid homeostasis that also have potent anti-inflammatory effects. The molecular basis for their anti-inflammatory effects is incompletely understood, but has been proposed to involve the indirect tethering of LXRs to inflammatory gene promoters. Here we demonstrate that the ability of LXRs to repress inflammatory gene expression in cells and mice derives primarily from their ability to regulate lipid metabolism through transcriptional activation and can occur in the absence of SUMOylation. Moreover, we identify the putative lipid transporter Abca1 as a critical mediator of LXR's anti-inflammatory effects. Activation of LXR inhibits signaling from TLRs 2, 4 and 9 to their downstream NF-κB and MAPK effectors through Abca1-dependent changes in membrane lipid organization that disrupt the recruitment of MyD88 and TRAF6. These data suggest that a common mechanism-direct transcriptional activation-underlies the dual biological functions of LXRs in metabolism and inflammation. },
}
|
|
2015
|
Tarling, Ahn, Aguiar Vallim (2015). The nuclear receptor FXR uncouples the actions of miR-33 from SREBP-2. Arterioscler Thromb Vasc Biol, 35(4), pp. 787-95. (bib)
x
@article{Tarling:2015aa,
bdsk-url-1 = { http://dx.doi.org/10.1161/ATVBAHA.114.304179 },
year = { 2015 },
volume = { 35 },
title = { The nuclear receptor FXR uncouples the actions of miR-33 from SREBP-2 },
pst = { ppublish },
pmid = { 25593129 },
pmc = { PMC4376635 },
pages = { 787-95 },
number = { 4 },
month = { Apr },
mesh = { ATP Binding Cassette Transporter 1; Animals; Binding Sites; Carnitine O-Palmitoyltransferase; Cell Line, Tumor; Cholesterol; Gene Expression Regulation; Humans; Intracellular Signaling Peptides and Proteins; Introns; Isoxazoles; Liver; Male; Membrane Proteins; Mice, Inbred C57BL; Mice, Knockout; MicroRNAs; Promoter Regions, Genetic; Quinolines; RNA, Messenger; Receptors, Cytoplasmic and Nuclear; Sterol Regulatory Element Binding Protein 2; Transcription, Genetic; Transfection },
keywords = { FXR; Nr1h4 protein, mouse; cholesterol; miR-33, mouse; sterol regulatory element binding protein 2 },
journal-full = { Arteriosclerosis, thrombosis, and vascular biology },
journal = { Arterioscler Thromb Vasc Biol },
doi = { 10.1161/ATVBAHA.114.304179 },
date-modified = { 2017-10-16 01:48:37 +0000 },
date-added = { 2017-10-16 01:48:37 +0000 },
author = { Tarling and Ahn and Aguiar Vallim },
abstract = { OBJECTIVE: To determine whether activation of farnesoid X receptor (FXR) alters cellular and plasma cholesterol homeostasis as a result of regulation of Srebp-2 and miR-33.
APPROACH AND RESULTS: Chromatin immunoprecipitation sequencing data identified an FXR response element within intron 10 of the Srebp-2 gene. Consistent with this observation, treatment of mice with FXR-specific agonists (GSK2324 or GW4064) rapidly increased hepatic levels of Srebp-2 mRNA, precursor sterol response element binding protein 2 (pSREBP-2) protein, and miR-33. Furthermore, miR-33 targets, that include ABCA1 (ATP binding cassette transporter A1), NSF (N-ethylmaleimide-sensitive factor), and CPT1 (carnitine palmitoyltransferase 1), were all reduced in GSK2324-treated mice. In contrast, neither nuclear SREBP-2 protein (nSREBP-2) nor SREBP-2 target genes were induced after FXR activation. The inability to process pSREBP-2 to nSREBP-2 is likely a consequence of the induction of insulin INSIG-2A (induced gene 2A) by FXR agonists. Finally, we show that FXR-dependent induction of both Srebp-2 and miR-33 is ablated in Scap(-/-) mice that lack nuclear SREBP-2.
CONCLUSIONS: We demonstrate that the activation of FXR uncouples the expression of nuclear SREBP-2 and miR-33, and the regulation of their respective target genes. Further, we conclude that the FXR agonist-dependent increase in miR-33 requires transcription of the Srebp-2 gene. },
}
|
|
2015
|
Aguiar Vallim, Tarling, Ahn, Hagey, Romanoski, Lee, Graham, Motohashi, Yamamoto, Edwards (2015). MAFG is a transcriptional repressor of bile acid synthesis and metabolism. Cell Metab, 21(2), pp. 298-310. (bib)
x
@article{Aguiar-Vallim:2015aa,
bdsk-url-1 = { http://dx.doi.org/10.1016/j.cmet.2015.01.007 },
year = { 2015 },
volume = { 21 },
title = { MAFG is a transcriptional repressor of bile acid synthesis and metabolism },
pst = { ppublish },
pmid = { 25651182 },
pmc = { PMC4317590 },
pages = { 298-310 },
number = { 2 },
month = { Feb },
mesh = { Animals; Bile Acids and Salts; Cell Line, Tumor; Hep G2 Cells; Humans; MafG Transcription Factor; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains },
journal-full = { Cell metabolism },
journal = { Cell Metab },
doi = { 10.1016/j.cmet.2015.01.007 },
date-modified = { 2017-10-16 01:48:51 +0000 },
date-added = { 2017-10-16 01:48:51 +0000 },
author = { Aguiar Vallim and Tarling and Ahn and Hagey and Romanoski and Lee and Graham and Motohashi and Yamamoto and Edwards },
abstract = { Specific bile acids are potent signaling molecules that modulate metabolic pathways affecting lipid, glucose and bile acid homeostasis, and the microbiota. Bile acids are synthesized from cholesterol in the liver, and the key enzymes involved in bile acid synthesis (Cyp7a1, Cyp8b1) are regulated transcriptionally by the nuclear receptor FXR. We have identified an FXR-regulated pathway upstream of a transcriptional repressor that controls multiple bile acid metabolism genes. We identify MafG as an FXR target gene and show that hepatic MAFG overexpression represses genes of the bile acid synthetic pathway and modifies the biliary bile acid composition. In contrast, loss-of-function studies using MafG(+/-) mice causes de-repression of the same genes with concordant changes in biliary bile acid levels. Finally, we identify functional MafG response elements in bile acid metabolism genes using ChIP-seq analysis. Our studies identify a molecular mechanism for the complex feedback regulation of bile acid synthesis controlled by FXR. },
}
|
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2014
|
Baldan, Gonen, Choung, Que, Marquart, Hernandez, Bjorkhem, Ford, Witztum, Tarling (2014). ABCG1 is required for pulmonary B-1 B cell and natural antibody homeostasis. J Immunol, 193(11), pp. 5637-48. (bib)
x
@article{Baldan:2014aa,
bdsk-url-1 = { http://dx.doi.org/10.4049/jimmunol.1400606 },
year = { 2014 },
volume = { 193 },
title = { ABCG1 is required for pulmonary B-1 B cell and natural antibody homeostasis },
pst = { ppublish },
pmid = { 25339664 },
pmc = { PMC4239162 },
pages = { 5637-48 },
number = { 11 },
month = { Dec },
mesh = { ATP Binding Cassette Transporter, Sub-Family G, Member 1; ATP-Binding Cassette Transporters; Adoptive Transfer; Animals; Antibodies; Atherosclerosis; Avian Proteins; B-Lymphocyte Subsets; B-Lymphocytes; Cells, Cultured; Cytokines; Gene Expression Profiling; Homeostasis; Lipid Metabolism, Inborn Errors; Lipoproteins; Lung; Lymphocyte Activation; Mice, Inbred C57BL; Mice, Knockout; Oxidation-Reduction; Phospholipids },
journal-full = { Journal of immunology (Baltimore, Md. : 1950) },
journal = { J Immunol },
doi = { 10.4049/jimmunol.1400606 },
date-modified = { 2017-10-16 01:46:43 +0000 },
date-added = { 2017-10-16 01:46:43 +0000 },
author = { Baldan and Gonen and Choung and Que and Marquart and Hernandez and Bjorkhem and Ford and Witztum and Tarling },
abstract = { Many metabolic diseases, including atherosclerosis, type 2 diabetes, pulmonary alveolar proteinosis, and obesity, have a chronic inflammatory component involving both innate and adaptive immunity. Mice lacking the ATP-binding cassette transporter G1 (ABCG1) develop chronic inflammation in the lungs, which is associated with the lipid accumulation (cholesterol, cholesterol ester, and phospholipid) and cholesterol crystal deposition that are characteristic of atherosclerotic lesions and pulmonary alveolar proteinosis. In this article, we demonstrate that specific lipids, likely oxidized phospholipids and/or sterols, elicit a lung-specific immune response in Abcg1(-/-) mice. Loss of ABCG1 results in increased levels of specific oxysterols, phosphatidylcholines, and oxidized phospholipids, including 1-palmitoyl-2-(5'-oxovaleroyl)-sn-glycero-3-phosphocholine, in the lungs. Further, we identify a niche-specific increase in natural Ab (NAb)-secreting B-1 B cells in response to this lipid accumulation that is paralleled by increased titers of IgM, IgA, and IgG against oxidation-specific epitopes, such as those on oxidized low-density lipoprotein and malondialdehyde-modified low-density lipoprotein. Finally, we identify a cytokine/chemokine signature that is reflective of increased B cell activation, Ab secretion, and homing. Collectively, these data demonstrate that the accumulation of lipids in Abcg1(-/-) mice induces the specific expansion and localization of B-1 B cells, which secrete NAbs that may help to protect against the development of atherosclerosis. Indeed, despite chronic lipid accumulation and inflammation, hyperlipidemic mice lacking ABCG1 develop smaller atherosclerotic lesions compared with controls. These data also suggest that Abcg1(-/-) mice may represent a new model in which to study the protective functions of B-1 B cells/NAbs and suggest novel targets for pharmacologic intervention and treatment of disease. },
}
|
|
2013
|
Bennett, Aguiar Vallim, Wang, Shih, Meng, Gregory, Allayee, Lee, Graham, Crooke, Edwards, Hazen, Lusis (2013). Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation. Cell Metab, 17(1), pp. 49-60. (bib)
x
@article{Bennett:2013aa,
bdsk-url-1 = { http://dx.doi.org/10.1016/j.cmet.2012.12.011 },
year = { 2013 },
volume = { 17 },
title = { Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation },
pst = { ppublish },
pmid = { 23312283 },
pmc = { PMC3771112 },
pages = { 49-60 },
number = { 1 },
month = { Jan },
mesh = { Androgens; Animals; Atherosclerosis; Base Sequence; Bile Acids and Salts; Choline; Diet; Down-Regulation; Female; Gene Silencing; HEK293 Cells; Humans; Male; Methylamines; Mice; Mice, Knockout; Oxygenases; Polymorphism, Single Nucleotide; Receptors, Cytoplasmic and Nuclear; Sex Factors },
journal-full = { Cell metabolism },
journal = { Cell Metab },
doi = { 10.1016/j.cmet.2012.12.011 },
date-modified = { 2017-10-16 01:44:44 +0000 },
date-added = { 2017-10-16 01:44:44 +0000 },
author = { Bennett and Aguiar Vallim and Wang and Shih and Meng and Gregory and Allayee and Lee and Graham and Crooke and Edwards and Hazen and Lusis },
abstract = { Circulating trimethylamine-N-oxide (TMAO) levels are strongly associated with atherosclerosis. We now examine genetic, dietary, and hormonal factors regulating TMAO levels. We demonstrate that two flavin mono-oxygenase family members, FMO1 and FMO3, oxidize trimethylamine (TMA), derived from gut flora metabolism of choline, to TMAO. Further, we show that FMO3 exhibits 10-fold higher specific activity than FMO1. FMO3 overexpression in mice significantly increases plasma TMAO levels while silencing FMO3 decreases TMAO levels. In both humans and mice, hepatic FMO3 expression is reduced in males compared to females. In mice, this reduction in FMO3 expression is due primarily to downregulation by androgens. FMO3 expression is induced by dietary bile acids by a mechanism that involves the farnesoid X receptor (FXR), a bile acid-activated nuclear receptor. Analysis of natural genetic variation among inbred strains of mice indicates that FMO3 and TMAO are significantly correlated, and TMAO levels explain 11% of the variation in atherosclerosis. },
}
|
|
2013
|
Rong, Albert, Hong, Duerr, Chamberlain, Tarling, Ito, Gao, Wang, Edwards, Jung, Ford, Tontonoz (2013). LXRs regulate ER stress and inflammation through dynamic modulation of membrane phospholipid composition. Cell Metab, 18(5), pp. 685-97. (bib)
x
@article{Rong:2013aa,
bdsk-url-1 = { http://dx.doi.org/10.1016/j.cmet.2013.10.002 },
year = { 2013 },
volume = { 18 },
title = { LXRs regulate ER stress and inflammation through dynamic modulation of membrane phospholipid composition },
pst = { ppublish },
pmid = { 24206663 },
pmc = { PMC3889491 },
pages = { 685-97 },
number = { 5 },
month = { Nov },
mesh = { 1-Acylglycerophosphocholine O-Acyltransferase; Animals; Cell Line; Cell Membrane; Endoplasmic Reticulum Stress; Fatty Acids; Humans; Inflammation; Inflammation Mediators; Liver; Liver X Receptors; Male; Membrane Microdomains; Mice; Orphan Nuclear Receptors; Phospholipids; Proto-Oncogene Proteins pp60(c-src); Signal Transduction },
journal-full = { Cell metabolism },
journal = { Cell Metab },
doi = { 10.1016/j.cmet.2013.10.002 },
date-modified = { 2017-10-16 01:45:10 +0000 },
date-added = { 2017-10-16 01:45:10 +0000 },
author = { Rong and Albert and Hong and Duerr and Chamberlain and Tarling and Ito and Gao and Wang and Edwards and Jung and Ford and Tontonoz },
abstract = { The fatty acyl composition of phospholipids determines the biophysical character of membranes and impacts the function of membrane proteins. Here, we define a nuclear receptor pathway for the dynamic modulation of membrane composition in response to changes in cellular lipid metabolism. Ligand activation of liver X receptors (LXRs) preferentially drives the incorporation of polyunsaturated fatty acids into phospholipids through induction of the remodeling enzyme Lpcat3. Promotion of Lpcat3 activity ameliorates endoplasmic reticulum (ER) stress induced by saturated free fatty acids in vitro or by hepatic lipid accumulation in vivo. Conversely, Lpcat3 knockdown in liver exacerbates ER stress and inflammation. Mechanistically, Lpcat3 modulates inflammation both by regulating inflammatory kinase activation through changes in membrane composition and by affecting substrate availability for inflammatory mediator production. These results outline an endogenous mechanism for the preservation of membrane homeostasis during lipid stress and identify Lpcat3 as an important mediator of LXR effects on metabolism. },
}
|
|
2013
|
Aguiar Vallim, Tarling, Kim, Civelek, Baldán, Esau, Edwards (2013). MicroRNA-144 regulates hepatic ATP binding cassette transporter A1 and plasma high-density lipoprotein after activation of the nuclear receptor farnesoid X receptor. Circ Res, 112(12), pp. 1602-12. (bib)
x
@article{Aguiar-Vallim:2013aa,
bdsk-url-1 = { http://dx.doi.org/10.1161/CIRCRESAHA.112.300648 },
year = { 2013 },
volume = { 112 },
title = { MicroRNA-144 regulates hepatic ATP binding cassette transporter A1 and plasma high-density lipoprotein after activation of the nuclear receptor farnesoid X receptor },
pst = { ppublish },
pmid = { 23519696 },
pmc = { PMC3995747 },
pages = { 1602-12 },
number = { 12 },
month = { Jun },
mesh = { 3' Untranslated Regions; ATP Binding Cassette Transporter 1; ATP-Binding Cassette Transporters; Animals; Apolipoprotein A-I; Cell Line, Tumor; Cholesterol, HDL; Gene Expression Regulation; HEK293 Cells; Hepatocytes; Humans; Isoxazoles; Mice; Mice, Inbred C57BL; Mice, Knockout; MicroRNAs; Quinolines; RNA Interference; Receptors, Cytoplasmic and Nuclear; Response Elements; Time Factors; Transfection },
keywords = { FXR; HDL-cholesterol; miRNA; nuclear receptor },
journal-full = { Circulation research },
journal = { Circ Res },
doi = { 10.1161/CIRCRESAHA.112.300648 },
date-modified = { 2017-10-16 01:46:08 +0000 },
date-added = { 2017-10-16 01:46:08 +0000 },
author = { Aguiar Vallim and Tarling and Kim and Civelek and Bald{\'a}n and Esau and Edwards },
abstract = { RATIONALE: The bile acid receptor farnesoid X receptor (FXR) regulates many aspects of lipid metabolism by variouscomplex and incompletely understood molecular mechanisms. We set out to investigate the molecular mechanisms for FXR-dependent regulation of lipid and lipoprotein metabolism.
OBJECTIVE: To identify FXR-regulated microRNAs that were subsequently involved in regulating lipid metabolism.
METHODS AND RESULTS: ATP binding cassette transporter A1 (ABCA1) is a major determinant of plasma high-density lipoprotein (HDL)-cholesterol levels. Here, we show that activation of the nuclear receptor FXR in vivo increases hepatic levels of miR-144, which in turn lowers hepatic ABCA1 and plasma HDL levels. We identified 2 complementary sequences to miR-144 in the 3' untranslated region of ABCA1 mRNA that are necessary for miR-144-dependent regulation. Overexpression of miR-144 in vitro decreased both cellular ABCA1 protein and cholesterol efflux to lipid-poor apolipoprotein A-I protein, whereas overexpression in vivo reduced hepatic ABCA1 protein and plasma HDL-cholesterol. Conversely, silencing miR-144 in mice increased hepatic ABCA1 protein and HDL-cholesterol. In addition, we used tissue-specific FXR-deficient mice to show that induction of miR-144 and FXR-dependent hypolipidemia requires hepatic, but not intestinal, FXR. Finally, we identified functional FXR response elements upstream of the miR-144 locus, consistent with direct FXR regulation.
CONCLUSIONS: We have identified a novel pathway involving FXR, miR-144, and ABCA1 that together regulate plasma HDL-cholesterol. },
}
|
|
2012
|
Martin, Lau, Singh, Vergnes, Tarling, Mehrabian, Mungrue, Xiao, Shih, Castellani, Ping, Reue, Stefani, Drake, Bostrom, Lusis (2012). ABCC6 localizes to the mitochondria-associated membrane. Circ Res, 111(5), pp. 516-20. (bib)
x
@article{Martin:2012aa,
bdsk-url-1 = { http://dx.doi.org/10.1161/CIRCRESAHA.112.276667 },
year = { 2012 },
volume = { 111 },
title = { ABCC6 localizes to the mitochondria-associated membrane },
pst = { ppublish },
pmid = { 22811557 },
pmc = { PMC3540978 },
pages = { 516-20 },
number = { 5 },
month = { Aug },
mesh = { ATP-Binding Cassette Transporters; Animals; Biotinylation; Calcinosis; Cardiovascular Diseases; Cell Fractionation; Cell Respiration; Gene Expression Regulation; Genes, Mitochondrial; Hepatocytes; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Knockout; Mitochondria; Mitochondrial Membranes; Pseudoxanthoma Elasticum },
journal-full = { Circulation research },
journal = { Circ Res },
doi = { 10.1161/CIRCRESAHA.112.276667 },
date-modified = { 2017-10-16 01:44:26 +0000 },
date-added = { 2017-10-16 01:44:26 +0000 },
author = { Martin and Lau and Singh and Vergnes and Tarling and Mehrabian and Mungrue and Xiao and Shih and Castellani and Ping and Reue and Stefani and Drake and Bostrom and Lusis },
abstract = { RATIONALE: Mutations of the orphan transporter ABCC6 (ATP-binding cassette, subfamily C, member 6) cause the connective tissue disorder pseudoxanthoma elasticum. ABCC6 was thought to be located on the plasma membrane of liver and kidney cells.
OBJECTIVE: Mouse systems genetics and bioinformatics suggested that ABCC6 deficiency affects mitochondrial gene expression. We therefore tested whether ABCC6 associates with mitochondria.
METHODS AND RESULTS: We found ABCC6 in crude mitochondrial fractions and subsequently pinpointed its localization to the purified mitochondria-associated membrane fraction. Cell-surface biotinylation in hepatocytes confirmed that ABCC6 is intracellular. Abcc6-knockout mice demonstrated mitochondrial abnormalities and decreased respiration reserve capacity.
CONCLUSIONS: Our finding that ABCC6 localizes to the mitochondria-associated membrane has implications for its mechanism of action in normal and diseased states. },
}
|
|
2011
|
Tarling, Edwards (2011). ATP binding cassette transporter G1 (ABCG1) is an intracellular sterol transporter. Proc Natl Acad Sci U S A, 108(49), pp. 19719-24. (bib)
x
@article{Tarling:2011aa,
bdsk-url-1 = { http://dx.doi.org/10.1073/pnas.1113021108 },
year = { 2011 },
volume = { 108 },
title = { ATP binding cassette transporter G1 (ABCG1) is an intracellular sterol transporter },
pst = { ppublish },
pmid = { 22095132 },
pmc = { PMC3241749 },
pages = { 19719-24 },
number = { 49 },
month = { Dec },
mesh = { ATP Binding Cassette Transporter, Sub-Family G, Member 1; ATP-Binding Cassette Transporters; Amino Acid Sequence; Animals; Benzoates; Benzylamines; Biological Transport; Blotting, Western; CHO Cells; COS Cells; Cells, Cultured; Cercopithecus aethiops; Cricetinae; Cricetulus; Endosomes; HEK293 Cells; Humans; Intracellular Space; Lipoproteins; Macrophages, Peritoneal; Molecular Sequence Data; Mutation; Sequence Homology, Amino Acid; Sterol Regulatory Element Binding Protein 2; Sterols; Transfection },
journal-full = { Proceedings of the National Academy of Sciences of the United States of America },
journal = { Proc Natl Acad Sci U S A },
doi = { 10.1073/pnas.1113021108 },
date-modified = { 2017-10-16 01:43:50 +0000 },
date-added = { 2017-10-16 01:43:50 +0000 },
author = { Tarling and Edwards },
abstract = { Four members of the mammalian ATP binding cassette (ABC) transporter G subfamily are thought to be involved in transmembrane (TM) transport of sterols. The residues responsible for this transport are unknown. The mechanism of action of ABCG1 is controversial and it has been proposed to act at the plasma membrane to facilitate the efflux of cellular sterols to exogenous high-density lipoprotein (HDL). Here we show that ABCG1 function is dependent on localization to intracellular endosomes. Importantly, localization to the endosome pathway distinguishes ABCG1 and/or ABCG4 from all other mammalian members of this superfamily, including other sterol transporters. We have identified critical residues within the TM domains of ABCG1 that are both essential for sterol transport and conserved in some other members of the ABCG subfamily and/or the insulin-induced gene 2 (INSIG-2). Our conclusions are based on studies in which (i) biotinylation of peritoneal macrophages showed that endogenous ABCG1 is intracellular and undetectable at the cell surface, (ii) a chimeric protein containing the TM of ABCG1 and the cytoplasmic domains of the nonsterol transporter ABCG2 is both targeted to endosomes and functional, and (iii) ABCG1 colocalizes with multiple proteins that mark late endosomes and recycling endosomes. Mutagenesis studies identify critical residues in the TM domains that are important for ABCG1 to alter sterol efflux, induce sterol regulatory element binding protein-2 (SREBP-2) processing, and selectively attenuate the oxysterol-mediated repression of SREBP-2 processing. Our data demonstrate that ABCG1 is an intracellular sterol transporter that localizes to endocytic vesicles to facilitate the redistribution of specific intracellular sterols away from the endoplasmic reticulum (ER). },
}
|
|
2010
|
Lee, Aguiar Vallim, Chong, Zhang, Liu, Jones, Osborne, Edwards (2010). Activation of the farnesoid X receptor provides protection against acetaminophen-induced hepatic toxicity. Mol Endocrinol, 24(8), pp. 1626-36. (bib)
x
@article{Lee:2010aa,
bdsk-url-1 = { http://dx.doi.org/10.1210/me.2010-0117 },
year = { 2010 },
volume = { 24 },
title = { Activation of the farnesoid X receptor provides protection against acetaminophen-induced hepatic toxicity },
pst = { ppublish },
pmid = { 20573685 },
pmc = { PMC2940469 },
pages = { 1626-36 },
number = { 8 },
month = { Aug },
mesh = { Acetaminophen; Animals; Cell Line; Cells, Cultured; Chromatin Immunoprecipitation; Hepatocytes; Liver; Mice; Mice, Inbred C57BL; Mice, Knockout; Oligonucleotide Array Sequence Analysis; Receptors, Cytoplasmic and Nuclear; Reverse Transcriptase Polymerase Chain Reaction },
journal-full = { Molecular endocrinology (Baltimore, Md.) },
journal = { Mol Endocrinol },
doi = { 10.1210/me.2010-0117 },
date-modified = { 2017-10-16 01:42:21 +0000 },
date-added = { 2017-10-16 01:42:21 +0000 },
author = { Lee and Aguiar Vallim and Chong and Zhang and Liu and Jones and Osborne and Edwards },
abstract = { The nuclear receptor, farnesoid X receptor (FXR, NR1H4), is known to regulate cholesterol, bile acid, lipoprotein, and glucose metabolism. In the current study, we provide evidence to support a role for FXR in hepatoprotection from acetaminophen (APAP)-induced toxicity. Pharmacological activation of FXR induces the expression of several genes involved in phase II and phase III xenobiotic metabolism in wild-type, but not Fxr(-/-) mice. We used chromatin immunoprecipitation-based genome-wide response element analyses coupled with luciferase reporter assays to identify functional FXR response elements within promoters, introns, or intragenic regions of these genes. Consistent with the observed transcriptional changes, FXR gene dosage is positively correlated with the degree of protection from APAP-induced hepatotoxicity in vivo. Further, we demonstrate that pretreatment of wild-type mice with an FXR-specific agonist provides significant protection from APAP-induced hepatotoxicity. Based on these findings, we propose that FXR plays a role in hepatic xenobiotic metabolism and, when activated, provides hepatoprotection against toxins such as APAP. },
}
|
|
2010
|
Jiang, Lu, Tarling, Kim, Man, Crumrine, Edwards, Elias, Feingold (2010). Regulation of ABCG1 expression in human keratinocytes and murine epidermis. J Lipid Res, 51(11), pp. 3185-95. (bib)
x
@article{Jiang:2010aa,
bdsk-url-1 = { http://dx.doi.org/10.1194/jlr.M006445 },
year = { 2010 },
volume = { 51 },
title = { Regulation of ABCG1 expression in human keratinocytes and murine epidermis },
pst = { ppublish },
pmid = { 20675829 },
pmc = { PMC2952559 },
pages = { 3185-95 },
number = { 11 },
month = { Nov },
mesh = { ATP Binding Cassette Transporter, Sub-Family G, Member 1; ATP-Binding Cassette Transporters; Animals; Cell Differentiation; Dose-Response Relationship, Drug; Epidermis; Female; Gene Expression Regulation; Gene Knockout Techniques; Humans; Hydrocarbons, Fluorinated; Keratinocytes; Lipoproteins; Liver X Receptors; Mice; Orphan Nuclear Receptors; PPAR delta; Permeability; RNA, Messenger; Sterols; Sulfonamides; Up-Regulation },
journal-full = { Journal of lipid research },
journal = { J Lipid Res },
doi = { 10.1194/jlr.M006445 },
date-modified = { 2017-10-16 01:42:38 +0000 },
date-added = { 2017-10-16 01:42:38 +0000 },
author = { Jiang and Lu and Tarling and Kim and Man and Crumrine and Edwards and Elias and Feingold },
abstract = { ABCG1, a member of the ATP binding cassette superfamily, facilitates the efflux of cholesterol from cells to HDL. In this study, we demonstrate that ABCG1 is expressed in cultured human keratinocytes and murine epidermis, and induced during keratinocyte differentiation, with increased levels in the outer epidermis. ABCG1 is regulated by liver X receptor (LXR) and peroxisome proliferator-activated receptor-δ (PPAR-δ) activators, cellular sterol levels, and acute barrier disruption. Both LXR and PPAR-δ activators markedly stimulate ABCG1 expression in a dose- and time-dependent fashion. PPAR-γ activators also increase ABCG1 expression, but to a lesser degree. In contrast, activators of PPAR-α, retinoic acid receptor, retinoid X receptor, and vitamin D receptor do not alter ABCG1 expression. In response to increased intracellular sterol levels, ABCG1 expression increases, whereas inhibition of cholesterol biosynthesis decreases ABCG1 expression. In vivo, ABCG1 is stimulated 3-6 h after acute barrier disruption by either tape stripping or acetone treatment, an increase that can be inhibited by occlusion, suggesting a potential role of ABCG1 in permeability barrier homeostasis. Although Abcg1-null mice display normal epidermal permeability barrier function and gross morphology, abnormal lamellar body (LB) contents and secretion leading to impaired lamellar bilayer formation could be demonstrated by electron microscopy, indicating a potential role of ABCG1 in normal LB formation and secretion. },
}
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2010
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Tarling, Bojanic, Tangirala, Wang, Lovgren-Sandblom, Lusis, Bjorkhem, Edwards (2010). Impaired development of atherosclerosis in Abcg1-/- Apoe-/- mice: identification of specific oxysterols that both accumulate in Abcg1-/- Apoe-/- tissues and induce apoptosis. Arterioscler Thromb Vasc Biol, 30(6), pp. 1174-80. (bib)
x
@article{Tarling:2010aa,
bdsk-url-1 = { http://dx.doi.org/10.1161/ATVBAHA.110.205617 },
year = { 2010 },
volume = { 30 },
title = { Impaired development of atherosclerosis in Abcg1-/- Apoe-/- mice: identification of specific oxysterols that both accumulate in Abcg1-/- Apoe-/- tissues and induce apoptosis },
pst = { ppublish },
pmid = { 20299684 },
pmc = { PMC2881948 },
pages = { 1174-80 },
number = { 6 },
month = { Jun },
mesh = { ATP Binding Cassette Transporter, Sub-Family G, Member 1; ATP-Binding Cassette Transporters; Animals; Apolipoproteins E; Apoptosis; Atherosclerosis; BH3 Interacting Domain Death Agonist Protein; Bone Marrow Transplantation; Brain; Caspase 3; Cells, Cultured; Cholesterol; Disease Models, Animal; Genotype; In Situ Nick-End Labeling; Lipoproteins; Lipoproteins, LDL; Macrophages; Mice; Mice, Knockout; Oxidation-Reduction; Phenotype; Proto-Oncogene Proteins c-bcl-2; RNA, Messenger; Time Factors },
journal-full = { Arteriosclerosis, thrombosis, and vascular biology },
journal = { Arterioscler Thromb Vasc Biol },
doi = { 10.1161/ATVBAHA.110.205617 },
date-modified = { 2017-10-16 01:43:08 +0000 },
date-added = { 2017-10-16 01:43:08 +0000 },
author = { Tarling and Bojanic and Tangirala and Wang and Lovgren-Sandblom and Lusis and Bjorkhem and Edwards },
abstract = { OBJECTIVE: To generate Abcg1(-/-) Apoe(-/-) mice to understand the mechanism and cell types involved in changes in atherosclerosis after loss of ABCG1.
METHODS AND RESULTS: ABCG1 is highly expressed in macrophages and endothelial cells, 2 cell types that play important roles in the development of atherosclerosis. Abcg1(-/-) Apoe(-/-) and Apoe(-/-) mice and recipient Apoe(-/-) mice that had undergone transplantation with bone marrow from Apoe(-/-) or Abcg1(-/-) Apoe(-/-) mice were fed a Western diet for 12 or 16 weeks before quantification of atherosclerotic lesions. These studies demonstrated that loss of ABCG1 from all tissues, or from only hematopoietic cells, was associated with significantly smaller lesions that contained increased numbers of TUNEL- and cleaved caspase 3-positive apoptotic Abcg1(-/-) macrophages. We also identified specific oxysterols that accumulate in the brains and macrophages of the Abcg1(-/-) Apoe(-/-) mice. These oxysterols promoted apoptosis and altered the expression of proapoptotic genes when added to macrophages in vitro.
CONCLUSIONS: Loss of ABCG1 from all tissues or from only hematopoietic cells results in smaller atherosclerotic lesions populated with increased apoptotic macrophages, by processes independent of ApoE. Specific oxysterols identified in tissues of Abcg1(-/-) Apoe(-/-) mice may be critical because they induce macrophage apoptosis and the expression of proapoptotic genes. },
}
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