Genetic ablation of lymphocytes and cytokine signaling in nonobese diabetic mice prevents diet-induced obesity and insulin resistance
AuthorsFriedline, Randall H.
Ko, Hwi Jin
Jung, Dae Young
Patel, Payal R.
Kearns, Caitlyn C.
Greiner, Dale L.
Kim, Jason K.
UMass Chan AffiliationsGraduate School of Biomedical Sciences, Interdisciplinary Graduate Program
UMass Metabolic Network
Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes
Diabetes Center of Excellence
Program in Molecular Medicine
Document TypeJournal Article
Keywordsdiabetes mouse models
Cellular and Molecular Physiology
MetadataShow full item record
AbstractObesity 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.
SourceFASEB J. 2016 Mar;30(3):1328-38. doi: 10.1096/fj.15-280610. Epub 2015 Dec 7. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/28827
Full author list omitted for brevity. For full list of authors see article.
Co-author Sezin Dagdeviren is a doctoral student in the Interdisciplinary Graduate Program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.
Related ResourcesLink to Article in PubMed