The Zang Laboratory at Barshop Institute and Department of Molecular Medicine investigates different aspects of fundamental metabolic and energetic processes in the liver and adipose tissues. The main goal of the Zang laboratory is to identify and characterize novel nutrient sensing pathways and their impact on glucose and lipid homeostasis.
We seek to develop new therapeutic strategies for obesity, diabetes, and fatty liver disease by building a better understanding of molecular mechanisms of nutrient sensing network. Recent studies from our laboratory have identified several nutrient sensors, such as AMP-activated protein kinase (AMPK), the NAD-dependent deacetylase (SIRT1), mechanistic target of rapamycin (mTOR), the hepatocyte-derived hormone FGF21, and retinoic acid receptor in studies published in Cell Metabolism, Diabetes, Gastroenterology, and Hepatology. Dysregulation of AMPK or SIRT1 appears to be involved in the pathogenesis of fatty liver disease and white adipose tissue fibrosis in obesity and type 2 diabetes.
We have also elucidated AMPK-dependent inhibition of de novo lipogenesis as a molecular mechanism for the beneficial effects of metformin, the most widely prescribed type 2 diabetes drugs, and polyphenols, on hepatic steatosis, hyperlipidemia, and atherogenesis in type 1 and type 2 diabetes. Further studies demonstrated that SIRT1 is functionally linked to FGF21 and the regulation of fatty acid metabolism, providing major therapeutic targets for the treatment of fatty liver disease. Our research will combine a variety of biochemical, cellular biology, metabolic and screening approaches both in cell culture and whole animals to identify the molecular mechanisms by which mammalian cells sense, communicate, and respond to nutrients. The ultimate goal is to provide new insight into the pathological mechanisms of diabetes and obesity as well as to identify potential therapeutic interventions of metabolic disease and age-associated metabolic diseases.
Other profile: See more at: http://molecularmedicine.uthscsa.edu/FAC_Research.aspx?facID=210
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.
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.
Li XY, Kover K, Heruth D, Watkins DJ, Moore WV, Zang M, Clements M, and Yun Yan. New insight into metformin action: regulation of ChREBP and FoXO1 activities in endothelial cells. Molecular Endocrinology, 2015; 29:1184-94.
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.
Li Y, Xu S, Jiang B, Cohen RA, Zang M. Activation of sterol regulatory element binding protein and NLRP3 inflammasome in atherosclerotic lesion development in diabetic pigs: Implications for human atherosclerosis progression. 2013; 8:e67532. doi:10.1371.
Li Y, Wong K, Walsh K, Gao B, Zang M. Retinoic acid receptor Î² 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
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.