University of Massachusetts Medical School Faculty Publications

Title

Genetic ablation of lymphocytes and cytokine signaling in nonobese diabetic mice prevents diet-induced obesity and insulin resistance

UMMS Affiliation

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

Date

3-1-2016

Document Type

Article

Disciplines

Cellular and Molecular Physiology | Endocrinology

Abstract

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.

Rights and Permissions

Citation: 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

Comments

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 Resources

Link to Article in PubMed

Keywords

diabetes mouse models, energy balance, glucose metabolism

PubMed ID

26644351