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Barshop Institute for Longevity and Aging Studies

Mengwei Zang, M.D., Ph.D.

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Mengwei Zang, M.D., Ph.D.

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Associate Professor of Molecular Medicine
Ewing Halsell Distinguished Chair
Sam and Ann Barshop Institute for Longevity and Aging Studies
Department of Molecular Medicine
University of Texas Health San Antonio
Phone: 210-562-4213

RESEARCH

Our research focuses on the mechanisms by which nutrient sensors regulate nutrient metabolism and energy homeostasis. We seek to identify new molecular targets that could be leveraged in the management of obesity, type 2 diabetes, fatty liver disease, and other age-related metabolic diseases. Our research goals are:

  1. To characterize novel nutrient-sensing pathways involved in the regulation of lipid metabolism and energy homeostasis using nutritionally challenged models, metabolic disease mouse models, genetically modified mouse models, pharmacologically treated mouse models, as well as cell/molecular biology. Current efforts are focused on the molecular mechanism(s) by which vitamin A-related retinoic acid receptors and the hepatocyte-derived hormone, FGF21, regulate metabolic homeostasis and how this regulation affects the progression of Type 2 diabetes and age-related metabolic disease.

  2. To identify the regulation and function of nutrient sensing and to characterize its therapeutic potential on non-alcoholic fatty liver disease. Current efforts are focused on the role of SIRT1 and AMP-activated protein kinase in the regulation of lipid metabolism in non-alcoholic fatty liver disease.

  3. To define the molecular mechanisms underlying the pathogenesis of alcoholic liver disease. Current efforts are focused on the role of the nutrient sensing network in the development of alcoholic fatty liver and liver injury.

  4. To investigate the role of nutrient sensing in adipose tissue metabolism and dysfunction. Although adipose tissue fibrosis impairs adipocyte plasticity, little is known about how aberrant extracellular matrix remodeling of fat tissue is initiated during the development of obesity. Our recent studies demonstrate the critical role of AMPK and TGFβ1 in adipocytes in the regulation of extracellular matrix homeostasis and systemic glucose metabolism in obese mice and humans. Targeting the AMPK pathway, like the action of metformin, may provide an exciting new approach for treatment of obesity-induced adipose tissue fibrosis and other tissue fibrosis.

SELECTIVE PUBLICATIONS:

Chen H, Shen F, Sherban A, Nocon A, Li Y, Wang H, Rui X, Han J, Jiang B, Li N, Keyhani-Nejad F, Fan J, Liu F, Kamat A, Musi N, Pacher P, Gao B, Zang M. DEP domain-containing mTOR-interacting protein suppresses lipogenesis and ameliorates hepatic steatosis and acute-on-chronic liver injury in alcoholic liver disease. Hepatology. 2018, doi: 10.1002/hep.29849.

Ramirez T, Li YM, Yin S, Xu MJ, Feng D, Zhou Z, Zang M, Mukhopadhyay P, Varga ZV, Pacher P, Gao B, Wang H. Aging aggravates alcoholic liver injury and fibrosis in mice by downregulating Sirtuin 1 expression. J Hepatol. 2017: S0168-8278(16) 30651-1.

Luo T, Nocon A, Fry J, Sherban A, Rui X, Jiang B, Xu XJ, Han J, Yan Y, Yang Q, Li Q, Zang M. AMPK activation by metformin suppresses abnormal adipose tissue extracellular matrix remodeling and ameliorates insulin resistance in obesity. Diabetes. 2016; 65:2295-2310.

Han J, Weisbrod RM, Shao D, Watanabe Y, Yin X, Bachschmid MM, Seta F, Janssen-Heininger YM, Matsui R, Zang M, Hamburg NM, Cohen RA. The redox mechanism for vascular barrier dysfunction associated with metabolic disorders: Glutathionylation of Rac1 in endothelial cells. Redox Biology. 2016; 306-319. doi: 10.1016/j.redox.2016.09.003.

Gong Q, Hu Z, Zhang F, Cui A, Chen X, Jiang H, Gao J, Chen X, Han Y, Liang Q, Ye D, Shi L, Eugene Chin Y, Wang Y, Xiao H, Guo F, Liu Y, Zang M, Xu A, Li Y. Fibroblast Growth Factor 21 Improves Hepatic Insulin Sensitivity by Inhibiting Mammalian Target of Rapamycin Complex 1. Hepatology. 2016; 64:425-438. PMID: 26926384.

Li Y, Wong K, Giles A, Lee JW, Jiang J, Adams AC, Kharitonenkov A, Yang Q, Gao B, Guarente L, Zang M. Hepatic SIRT1 attenuates hepatic steatosis and controls energy balance in mice by inducing fibroblast growth factor 21. Gastroenterology. 2014; 146: 539-549. PMID: 24184811.

Li Y, Wong K, Walsh K, Gao B, Zang M. Retinoic acid receptor β stimulates hepatic induction of fibroblast growth factor 21 to promote fatty acid oxidation and control whole-body energy homeostasis in mice. Journal of Biological Chemistry. 2013; 288: 10490-10540.

Li Y, Xu S, Mihaylova M, Zheng B, Hou X, Jiang B, Park O, Luo Z, Lefai E, Shyy JY, Gao B, Wierzbicki M, Verbeuren TJ, Shaw RJ, Cohen RA, Zang M. AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin resistant mice. Cell Metabolism. 2011; 13: 376-388. Selected as the most cited article in Cell Metabolism in 2011

Li Y, Xu S, Giles A, Nakamura K, Lee JW, Hou X, Donmez G, Li J, Luo Z, Walsh K, Guarente L, Zang M. Hepatic overexpression of SIRT1 in mice attenuates endoplasmic reticulum stress and insulin resistance in the liver. FASEB Journal. 2011; 25: 1664-1679.

Hou X, Xu S, Maitland-Toolan KA, Sato K, Jiang B, Ido Y, Lan F, Walsh K, Wierzbicki M, Verbeuren TJ, Cohen RA, Zang M. SIRT1 regulates hepatocyte lipid metabolism through activating AMP-Activated protein kinase. Journal of Biological Chemistry. 2008; 283: 20015-20026. Faculty of 1000 Biology.


 
 
   
 

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The Sam and Ann Barshop Institute for Longevity and Aging Studies

15355 Lambda Drive
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P: 210-562-6140 F: 210-562-6150

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