The Metabolism Core is designed to conduct in vivo and physiological experiments in conscious mice for the purpose of detailed metabolic phenotyping of transgenic mouse models useful for understanding obesity, diabetes and its complications. The Core operates under the supervision of Drs. Jason Kim (Director), Dae Young Jung (co-Director), and Hwi Jin Ko (co-Director) who oversee day-to-day operation of the Core and interact with the users of the UMass MMPC. The principal functions of the Core are to perform the following experiments: 1) hyperinsulinemic-euglycemic clamp to assess organ-specific insulin action and glucose metabolism in conscious mice, 2) hyperglycemic clamp to assess in vivo pancreatic beta-cell function in conscious mice, 3) iv or ip glucose/insulin tolerance tests, 4) survival surgery of jugular vein cannulation for in vivo experiments, 5) implementation of osmotic pumps for chronic delivery of drugs or other agents, 6) application of special diet (e.g.. high-fat diet) to alter energy balance and induce obesity in mice. 7) acute lipid infusion, acute/chronic delivery of cytokines and phloridzin, and STZ injection to alter glucose homeostasis. 8) non-invasive measurement of energy expenditure, respiratory exchange ratio, physical activity, and food/water intake in conscious mice using metabolic cages. 9) non-invasive assessment of whole body, organ, and tissue biopsy composition of fat/lean/water mass in conscious mice using 1 H-MRS. 10) implementation of cage wheel for exercise study, and 12) biochemical analysis for intracellular metabolic flux measurement (glycolysis, glycogen synthesis). The Metabolism Core regulariy interacts with the Analytical Core for complementary, high-throughput analytical assays to measure hormones, cytokines and metabolites using serum samples obtained at the end of metabolic experiments. Also, the Metabolism Core interacts and with the Cardiovascular Complications Core for additional phenotyping associated with cardiovascular functions. The goal of the Metabolism Core is to use an array of elegant, non-invasive and in vivo experiments to obtain a robust set of metabolic data from individual mouse in order to provide mechanistic insights into the role of selected gene on obesity, insulin resistance, and diabetes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Resource-Related Research Projects--Cooperative Agreements (U24)
Project #
5U24DK093000-04
Application #
8708056
Study Section
Special Emphasis Panel (ZDK1-GRB-S)
Project Start
Project End
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
4
Fiscal Year
2014
Total Cost
$246,750
Indirect Cost
$96,750
Name
University of Massachusetts Medical School Worcester
Department
Type
DUNS #
603847393
City
Worcester
State
MA
Country
United States
Zip Code
01655
Vernia, Santiago; Cavanagh-Kyros, Julie; Garcia-Haro, Luisa et al. (2014) The PPAR?-FGF21 hormone axis contributes to metabolic regulation by the hepatic JNK signaling pathway. Cell Metab 20:512-25
Tao, Hanlin; Zhang, Yong; Zeng, Xiangang et al. (2014) Niclosamide ethanolamine-induced mild mitochondrial uncoupling improves diabetic symptoms in mice. Nat Med 20:1263-9
Mori, Marcelo A; Thomou, Thomas; Boucher, Jeremie et al. (2014) Altered miRNA processing disrupts brown/white adipocyte determination and associates with lipodystrophy. J Clin Invest 124:3339-51
Pan, Dongning; Mao, Chunxiao; Quattrochi, Brian et al. (2014) MicroRNA-378 controls classical brown fat expansion to counteract obesity. Nat Commun 5:4725
Jung, Dae Young; Ko, Hwi Jin; Lichtman, Eben I et al. (2013) Short-term weight loss attenuates local tissue inflammation and improves insulin sensitivity without affecting adipose inflammation in obese mice. Am J Physiol Endocrinol Metab 304:E964-76
Hong, Eun-Gyoung; Kim, Brian W; Jung, Dae Young et al. (2013) Cardiac expression of human type 2 iodothyronine deiodinase increases glucose metabolism and protects against doxorubicin-induced cardiac dysfunction in male mice. Endocrinology 154:3937-46
Han, Myoung Sook; Jung, Dae Young; Morel, Caroline et al. (2013) JNK expression by macrophages promotes obesity-induced insulin resistance and inflammation. Science 339:218-22
Guo, Chang-An; Kogan, Sophia; Amano, Shinya U et al. (2013) CD40 deficiency in mice exacerbates obesity-induced adipose tissue inflammation, hepatic steatosis, and insulin resistance. Am J Physiol Endocrinol Metab 304:E951-63
Meng, Zhuo-Xian; Li, Siming; Wang, Lin et al. (2013) Baf60c drives glycolytic metabolism in the muscle and improves systemic glucose homeostasis through Deptor-mediated Akt activation. Nat Med 19:640-5
Jung, Dae Young; Chalasani, Umadevi; Pan, Ning et al. (2013) KLF15 is a molecular link between endoplasmic reticulum stress and insulin resistance. PLoS One 8:e77851

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