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Genetic ablation of lymphocytes and cytokine signaling in nonobese diabetic mice prevents diet‐induced obesity and insulin resistance
Author(s) -
Friedline Randall H.,
Ko Hwi Jin,
Jung Dae Young,
Lee Yongjin,
Bortell Rita,
Dagdeviren Sezin,
Patel Payal R.,
Hu Xiaodi,
Inashima Kunikazu,
Kearns Caitlyn,
Tsitsilianos Nicholas,
Shafiq Umber,
Shultz Leonard D.,
Lee Ki Won,
Greiner Dale L.,
Kim Jason K.
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.15-280610
Subject(s) - insulin resistance , endocrinology , medicine , nod , insulin receptor , cytokine , insulin , immune system , biology , diabetes mellitus , type 2 diabetes , obesity , nod mice , immunology
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 g 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 ~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 (~10%) and physical activity (~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.—Friedline, R. H., Ko, H.J., Jung, D. Y., Lee, Y., Bortell, R., Dagdeviren, S., Patel, P. R., Hu, X., Inashima, K., Kearns, C., Tsitsilianos, N., Shafiq, U., Shultz, L. D., Lee, K. W., Greiner, D. L., Kim, J. K., Genetic ablation of lymphocytes and cytokine signaling in nonobese diabetic mice prevents diet‐induced obesity and insulin resistance. FASEB J. 30, 1328–1338 (2016). www.fasebj.org