Genetic ablation of lymphocytes and cytokine signaling in nonobese diabetic mice prevents diet-induced obesity and insulin resistance
Program in Molecular Medicine; Diabetes Center of Excellence; Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes; UMass Metabolic Network; Graduate School of Biomedical Sciences, Interdisciplinary Graduate Program
Cellular and Molecular Physiology | Endocrinology
Obesity is characterized by a dysregulated immune system, which may causally associate with insulin resistance and type 2 diabetes. Despite widespread use of nonobese diabetic (NOD) mice, NOD with severe combined immunodeficiency (scid) mutation (SCID) mice, and SCID bearing a null mutation in the IL-2 common gamma chain receptor (NSG) mice as animal models of human diseases including type 1 diabetes, the underlying metabolic effects of a genetically altered immune system are poorly understood. For this, we performed a comprehensive metabolic characterization of these mice fed chow or after 6 wk of a high-fat diet. We found that NOD mice had approximately 50% less fat mass and were 2-fold more insulin sensitive, as measured by hyperinsulinemic-euglycemic clamp, than C57BL/6 wild-type mice. SCID mice were also more insulin sensitive with increased muscle glucose metabolism and resistant to diet-induced obesity due to increased energy expenditure ( approximately 10%) and physical activity ( approximately 40%) as measured by metabolic cages. NSG mice were completely protected from diet-induced obesity and insulin resistance with significant increases in glucose metabolism in peripheral organs. Our findings demonstrate an important role of genetic background, lymphocytes, and cytokine signaling in diet-induced obesity and insulin resistance.
diabetes mouse models, energy balance, glucose metabolism
DOI of Published Version
FASEB J. 2016 Mar;30(3):1328-38. doi: 10.1096/fj.15-280610. Epub 2015 Dec 7. Link to article on publisher's site
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Friedline, Randall H.; Ko, Hwi Jin; Jung, Dae Young; Lee, Yongjin; Bortell, Rita; Dagdeviren, Sezin; Patel, Payal R.; Hu, Xiaodi; Inashima, Kunikazu; Kearns, Caitlyn C.; Tsitsilianos, Nicholas; Shafiq, Umber; Greiner, Dale L.; and Kim, Jason K., "Genetic ablation of lymphocytes and cytokine signaling in nonobese diabetic mice prevents diet-induced obesity and insulin resistance" (2016). University of Massachusetts Medical School Faculty Publications. 1066.