Bingzhong Xue
Assistant Professor of Endocrinology and Metabolism 
M.D.., 1992 Shanghai Medical University (China)
Ph.D., 2000 University of Tennessee - Knoxville

Obesity is associated with a variety of health problems, including insulin resistance, type II diabetes, cardiovascular disease and some types of cancer, which, collectively, post a serious health threat to humans.

It is now well defined that inflammation plays a key role in obesity and its associated health problems, such as insulin resistance and type II diabetes. Obesity is associated with a chronic inflammatory state characterized by macrophage infiltration into the adipose tissue, excess production of pro-inflammatory cytokines such as tumor necrosis factor-α by adipocytes and other cytokine-producing cells, and activation of inflammatory signaling networks, which in turn down-regulate insulin signaling pathway, leading to insulin resistance.

My Lab is interested in studying the role of AMP-activated protein kinase (AMPK) in the regulation of obesity induced inflammation and insulin resistance. AMPK is an evolutionarily well preserved serine/threonine kinase that serves as a cellular energy sensor. It is activated by increased AMP/ATP ratios induced by a range of physiological and pathological conditions, such as muscle contraction and exercise, hypoxia, ischemia, glucose deprivation and uncouplers of oxidative phosphorylation. Once activated, AMPK down-regulates ATP-consuming processes and up-regulates ATP-producing pathways. AMPK plays an important role in glucose, fatty acids, cholesterol and protein metabolism and glucose/energy homeostasis.

During the recent years it has been shown that activation of AMPK suppresses pro-inflammatory cytokine production and inhibits NF-κB activation, thereby attenuates inflammation. My Lab is using both in vitro cell culture system and in vivo animal models to delineate the role of AMPK in the regulation of obesity-induced inflammation and insulin resistance. Specifically, we are studying whether expression of AMPK in adipocytes or cells with myeloid lineage (including macrophages) modifies obesity-induced inflammation and insulin resistance. In addition, we are using molecular biology techniques to study the mechanisms mediating AMPK’s anti-inflammatory effect, including modification of NF-κB pathway as well as possible involvement of epigenetic regulation of inflammation by AMPK. Lastly, we are studying the up-stream signaling pathways that regulate AMPK’s anti-inflammatory effect, including signaling pathways originating from central nervous system.

Recent Publications (selected):

1.       Xue B., Moustaid N. Wilkison W.O. and Zemel M. The agouti gene product inhibits lipolysis in human adipocytes via a Ca²⁺-dependent mechanism. FASEB J. 1998;  12: 1391-1396

2.       Xue B. Z., Wilkison W.O., Mynatt R.L., Moustaid N., Goldman M. and Zemel M. B. The agouti gene product stimulates pancreatic b-cell Ca²⁺ signaling and insulin release. Physiol. Genomics. 1999; 1: 11-19

3.       Claycombe K., Xue B. Z., Mynatt R. J., Wilkison W. O., Zemel M. B. and Moustaid-Moussa N. Regulation of leptin by agouti and insulin. Physiol. Genomics. 2000; 2 (3): 101-105

4.       Xue B.. and Zemel M. B. Relationship between human adipose tissue agouti and fatty acid synthase (FAS). J. Nutr. 2000; 130 (10): 2478-2481

5.       Xue, B.  and Zemel M. B. The agouti gene product stimulates islet amyloid polypeptide (amylin) secretion in pancreatic b-cells. Exp. Biol. Med. 2001; 226 (6): 565-569

6.       Xue, B., Greenberg A. G., Kraemer F. B. and Zemel M. B. Mechanism of intracellular calcium ([Ca²⁺]i) inhibition of lipolysis in human adipocytes. FASEB J. 2001; 15 (13): 2527-2529

7.       Minokoshi Y, Alquier T, Furukawa N, Kim YB, Lee A, Xue B, Mu J, Foufelle F, Ferre P, Birnbaum MJ, Stuck BJ and Kahn BB. AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus. Nature. 2004  428 (6982): 569-574.

8.       Rim JS, Xue B, Gawronska-Kozak B and Kozak LP. Sequestration of Thermogenic Transcription Factors in the Cytoplasm during Development of Brown Adipose Tissue. J Biol Chem. 2004; 279 (24): 25916-26.

9.       Xue B., Coulter A., Rim J. S., Koza R. A. And Kozak L. P. Transcriptional synergy and the regulation of Ucp1 during brown adipocyte induction in white fat depots. Mol. Cell. Biol. 2005. 25: 8311-8322.

10.   Bence K. K., Delibegovic M., Xue B., Gorgun C. Z., Hotamisligil G. S., Neel B. G. and Kahn B. B. Neuronal PTP1B regulates body weight, adiposity and leptin action. Nat. Med. 2006. 12: 917-924.

11.   Xue B., Rim J. S., Hogan J. C., Coulter A. A., Koza R. A. and Kozak L. P. Genetic variability affects the development of brown adipocytes in white fat but not in interscapular brown fat. J. Lipid Res. 2007. 48: 41-51.

12.   Kennedy A. R., Pissios P., Out H., Xue B., Asakura K., Furukawa N., Marino F. E., Liu F. F., Kahn B. B., Litermann T. A. and Maratos-Flier E. A high-fat, ketogenic diet induces a unique metabolic state in mice. Am. J. Physiol. Endocrinol. Metab. 2007. 292: E1724-1739.

13.   Xue B., Kim Y. B., Lee A., Toschi E., Bonner-Weir S., Kahn C. R., Neel B. G. and Kahn B. B. Protein tyrosine phosphatase 1B (PTP1B) deficiency reduces insulin resistance and the diabetic phenotype in mice with polygenic insulin resistance. J. Bio. Chem. 2007. 282: 23829-23840.