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Barshop Institute for Longevity and Aging Studies

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


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

Associate Professor
Ewing Halsell Distinguished Chair
Department of Molecular Medicine
Barshop Institute for Longevity and Aging Studies
UT Health Science Center at San Antonio
Phone: 210-562-4213


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 aging-related metabolic diseases.

  1. To seek 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, and 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 obesity-induced Type 2 diabetes and aging-related metabolic disease.
  2. To identify the regulation and function of nutrient sensing and characterize the therapeutic potential on non-alcoholic fatty liver disease. Current efforts are focused on the role of SIRT1, AMP-activated protein kinase, and FGF21 in the regulation of hepatic glucose and lipid metabolism in diabetes and non-alcoholic fatty liver disease.
  3. To define the molecular mechanisms underlying the pathogenesis of alcoholic liver disease. 

My laboratory's studies have discovered that dysregulation of the nutrient sensor AMP-activated protein kinase (AMPK) in the liver contributes to the pathogenesis of hepatic steatosis, hyperlipidemia, vascular inflammation and atherosclerosis in type 1 and type 2 diabetes (Zang M, et al., JBC, 2004, Diabetes, 2006; Hou X, et al., JBC, 2008; Li Y, et al., Cell Metabolism, 2011). Our new research direction investigates the new role of nutrient sensing in adipose tissue metabolism and function. Emerging evidence indicates that people with obesity and type 2 diabetes have increased adipose tissue interstitial fibrosis and reduced insulin action. Furthermore, higher levels of TGFβ1 in adipose tissue and serum are associated with increased risk of developing type 2 diabetes. 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 new findings published in Diabetes (Ting L, et al, Diabetes, 2016) demonstrated the critical role of AMPK in adipocytes in the regulation of extracellular matrix homeostasis and systemic glucose metabolism in obese mice and humans. Our studies showed that AMPK suppression in adipocytes was associated with accumulated collagen content and deposition in white adipose tissue, and elevated fasting blood glucose levels in obese mice. Our translational studies also showed a strong association between decreased AMPK and increased TGFβ1 in visceral white adipose tissue and other components of the metabolic syndrome in overweight/obese individuals. Our studies showed that the outcomes of reduced AMPK activity in adipocytes in vitro mimicked the downregulation of AMPK in adipocytes in patients with obesity. This led to mechanistic studies in which we determined how this “dysfunction” of adipocytes results in insulin resistance. These studies suggest that inactivation of AMPK in white adipose tissue would be a useful marker to predict the risk of the metabolic syndrome in patients with metabolically unhealthy expanding adipose tissue. Strikingly, activation of AMPK with metformin in vitro or in vivo is sufficient to reduce TGFβ1 activation and fibrotic response in white adipose tissue and to enhance insulin sensitivity.

This study also led to our discovery that AMPK serves as a novel suppressor of TGFβ1 activity that promotes abnormal extracellular matrix remodeling in adipose tissue and decreases whole-body insulin sensitivity in obesity.  This major mechanism may represent the previously undescribed function of metformin on the improvement of obesity-induced adipose tissue dysfunction and insulin resistance. Targeting AMPK pathway, like the action of metformin, may provide an exciting new approach for prevention and treatment of obesity and fibrotic disease.


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, 2018 Feb 19. 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* (*Corresponding author). 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.


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