Xue, Bingzhong - Georgia State University

个人简介

Ph.D. Nutrition University of Tennessee at Knoxville, 2000 Regulation of energy Homeostasis

研究领域

Brown adipocyte biology Central regulation of energy homeostasis Macrophage inflammation, insulin resistance and athersclerosis My research focuses on the molecular basis of energy homeostasis, including both central and peripheral regulation of energy balance, insulin sensitivity, lipid and cholesterol metabolism, and brown and white adipocyte biology, by using transgenic/knockout models, molecular biology techniques and physiological approaches. One of my research interests is to understand the mechanisms mediating the induction of brown adipocytes in white fat depot. Unlike white fat, which serves as energy storage depot, the function of brown fat is to maintain body temperature during cold stress by generating heat through the uncoupling of oxidative phosphorylation via the uncoupling protein 1 (UCP1). Cold exposure or adrenergic stimulation induces the appearance of brown adipocytes in traditional white fat depots in rodents and other small animals, as demonstrated by their multilocular morphology, abundant mitochondria and the expression of the brown fat-specific UCP1. This inducible brown adipocyte phenotype is significant since it reverses both diet-induced and genetic obesity. Importantly, recent data demonstrate that metabolically active brown adipose tissue also exists in adult humans. Therefore, inducing brown adipocytes in white fat may represent a novel approach in the prevention and treatment of obesity. Currently, we are studying the mechanisms by which brown adipocytes can be induced in white fat depots using cellular and molecular biology techniques, whole genome profiling approaches and genetically engineered mouse models. Another part of my research is to understand how energy homeostasis is regulated through hypothalamic neuronal network. Obesity results from imbalance between energy intake and energy expenditure. Hypothalamus is the center in the regulation of energy homeostasis. The different neurons in the hypothalamus receive and integrate signals from the periphery and send signals to higher brain centers, which corporately regulate food intake and energy expenditure, thereby maintaining energy homeostasis. We are currently interested in how hypothalamic neuronal network adapts and being re-programmed in obesity, which may be an underlying mechanism in the development of the metabolic syndrome. Last but not least, I am studying the role of macrophage AMPK in the protection against insulin resistance and atherosclerosis. Macrophage inflammation plays a key role in the development of metabolic disorders including insulin resistance and atherosclerosis. Inflammatory responses in obesity can be activated by altered nutrient metabolism (e.g. excess lipids and modified lipoprotein particles). High levels of cholesterol and saturated fatty acids (SFAs) alter macrophage function and result in macrophage abnormalities by inducing macrophage endoplasmic reticulum (ER) stress. ER stress has been linked to a wide range of complex diseases, including obesity, diabetes and atherosclerosis. AMP-activated protein kinase (AMPK) is an evolutionally conserved cellular energy sensor that regulates metabolic pathways in lipid, cholesterol and glucose metabolism. We have previously reported that macrophage AMPK protects against lipid-induced inflammation and insulin resistance in vitro. Therefore, we are currently studying whether macrophage AMPK protects against obesity-associated insulin resistance and atherosclerosis in animal models and whether this is mediated through AMPK’s regulation of macrophage lipid and cholesterol homeostasis, which leads to the protection against lipid- and cholesterol-induced ER stress.

近期论文

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Guo F, Ma Y, Kadegowda AK, Xie P, Liu G, Liu X, Miao H, Ou J, Su X, Zheng Z, Xue B, Shi H, Yu L. Deficiency of Liver Comparative Gene Identification-58 (CGI-58) Causes Steatohepatitis and Fibrosis in Mice. J Lipid Res. 2013 Aug; 54(8):2109-20. doi: 10.1194/jlr.M035519. Epub 2013 Jun 3. PMCID: PMC3708361 Yang, Z., Wang, X., He, Y., Qi, L., Xue, B.*, and Shi, H*. (* Co-corresponding authors). The capacity of AICAR to reduce obesity-induced inflammation and insulin resistance requires myeloid SIRT1. PLoS ONE, 2012; 7 (11): e49935. doi: 10.1371/journal.pone.0049935. Epub 2012 Nov 21. PMCID: PMC3503857 Xue, B.*, Wang, X., Yang, Z., Shi, H*.(* Co-corresponding authors). w-3 polyunsaturated fatty acids antagonize macrophage inflammation via activation of AMPK/SIRT1 pathway. PLoS ONE, 2012; 7 (10): e45990. doi: 10.1371/journal.pone.0045990.Epub 2012 Oct. 5. PMCID: PMC3465287 Yang, Z., Hulver, M., McMillan, R. P., Kershaw, E. E., Yu, L., Xue, B.*, and Shi, H*. (* Co-corresponding authors). Regulation of leptin and insulin action by muscle suppressor of cytokine signaling 3 (SOCS3). PLoS ONE, 2012; 7 (10): e47493. doi: 10.1371/journal.pone.0047493. Epub 2012 Oct. 24. PMCID: PMC3480378 Delbono O, Messi ML, Wang ZM, Treves S, Mosca B, Bergamelli L, Nishi M, Takeshima H, Shi H, Xue B, Zorzato F. Endogenously determined restriction of food intake overcomes excitation-contraction uncoupling in JP45KO mice with aging. Exp. Gerontology. 2012, 47: 304-316. PMCID: PMC3307889 Wang, X., Yang, Z., Xue, B.* and Shi, H.* (* Co-corresponding authors). Activation of the cholinergic anti-inflammatory pathway ameliorates obesity-induced inflammation and insulin resistance. Endocrinology 2011. 152 (3): 836-846. PMCID: PMC3040050. Editorial Commentary Article. Yang,Z., Kahn, B.B., Shi,H. and UXue, B.ZU. Macrophage α1AMP-activated protein kinase (α1AMPK) antagonizes fatty acid-induced inflammation through SIRT1. J. Biol. Chem. 2010. 285 (25): 19051-19059. PMCID: PMC2885183. Brown J.M., Betters J.L., Lord C.,Ma Y., Han X., Yang K., Alger H.M., Melchior J., Sawyer J., Shah R., Wilson M.D., Liu X., Graham M.J., Lee R., Cooke R., Shulman G.I., UXue B.U, Shi H. and Yu L. CGI-58 knockdown in mice causes hepatic steatosis, but prevents diet-induced obesity and glucose intolerance. J. Lipid Res. 2010; 51: 3306-3315. PMCID: PMC2952571. UXue, B.U, Pulinilkunnil, T., Murano, I., Bence, K. K., He, H., Minokoshi, Y., Asakura, K., Lee, A., Haj, F., Furukawa, N., Balschi, J. A., Cinti, S., Neel, B. G. and Kahn, B. B. Neuronal PTP1B Deficiency Results in Inhibition of Hypothalamic AMPK and Isoform-Specific Activation of AMPK in Peripheral Tissues. Mol. Cell. Biol. 2009. 29 (16): 4563-4573. PMCID: PMC2725736. Sutton, B. S., Palmer, N. D., Langefeld, C. D., Xue, B. Z., Proctor, A., Ziegler, J. T., Haffner, S. M., Norris, J. M. and Bowden, D. W. Association of SSTR2 polymorphisms and glucose homeostasis phenotypes: the Insulin Resistance Atherosclerosis Family Study. Diabetes. 2009 Jun;58(6):1457-62. PMCID: PMC2682669 UXue B.U, 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. Kennedy A. R., Pissios P., Out H., UXue B.U, 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. UXue B.U, 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. Bence K. K., Delibegovic M., UXue B.U, 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. UXue B.U, 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. PMCID: PMC1234324 Rim JS, UXue BU, 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. Minokoshi Y, Alquier T, Furukawa N, Kim YB, Lee A, UXue BU, 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. UXue, B.U, 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