The overall goal of research in the Zang laboratory is to understand the fundamental regulation of nutrient sensing network in lipid metabolism and insulin action as well as to translate these basic research findings into potential targeted therapies for obesity, type 1 and type 2 diabetes, non-alcoholic liver disease (NAFLD), and alcoholic liver disease (ALD). Major research interests include identifying novel nutrient sensing pathways involved in the regulation of cell metabolism and insulin sensitivity; discovering the mechanisms by which novel hepatocyte-secreted molecules alter fuel metabolism and insulin action; and determining the molecular mechanisms that make obesity a risk factor for type 2 diabetes. Zang laboratory employs a variety of approaches, such as protein kinase/phosphorylation, gene regulation, in vivo adenoviral gene delivery, genetic knockout mice, and pharmacological approaches. Her work has had a major impact on understanding the regulation and function of master nutrient sensors, such as AMP-activated protein kinase, the NAD+-dependent deacetylase SIRT1, vitamin A-related retinoic acid receptor, and the recently identified hepatocyte-derived hormone fibroblast growth factor 21 (FGF21). Her work has demonstrated that pharmacological activation of AMPK by polyphenols or metformin can phosphorylate sterol regulatory element-binding protein (SREBP), a key lipogenic factor in the liver, suppress SREBP-dependent lipogenesis in hepatocytes, and slow the progression of hepatic steatosis and aortic atherosclerosis in obesity-induced insulin resistance and diabetes. In addition, Zang laboratory has established a critical role of the FGF21 pathway in mediating liver SIRT1 actions on lipid hemostasis and whole-body energy balance. Her laboratory’s studies have also proposed a critical role of the liver as an endocrine organ and led to the discovery of the hepatocyte-secreted protein FGF21 action in the regulation of the liver-adipose tissue crosstalk and energy balance. Studies from her laboratory have substantially contributed to the current pharmaceutical interest in AMPK, SIRT1, and FGF21 as promising drug targets for treating type 2 diabetes and NAFLD.
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 in mice. Hepatology, 2016; Feb 29. doi: 10.1002/hep.28523. [Epub ahead of print].
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. PMCID: PMC4228483.
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. PLoS One, 2013; 8: e67532. doi:10.1371. PMCID: 3692453.