title: Genetic ablation of lymphocytes and cytokine signaling in nonobese diabetic mice prevents diet-induced obesity and insulin resistance.
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 γ 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.
authors.affiliation: *Program in Molecular Medicine, Diabetes Center of Excellence, and Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA; The Jackson Laboratory, Bar Harbor, Maine, USA; and World Class University Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea.
authors.forename: Randall H
authors.initials: RH
authors.lastname: Friedline
authors.affiliation: *Program in Molecular Medicine, Diabetes Center of Excellence, and Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA; The Jackson Laboratory, Bar Harbor, Maine, USA; and World Class University Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea.
authors.forename: Hwi Jin
authors.initials: HJ
authors.lastname: Ko
authors.affiliation: *Program in Molecular Medicine, Diabetes Center of Excellence, and Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA; The Jackson Laboratory, Bar Harbor, Maine, USA; and World Class University Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea.
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Jung
authors.affiliation: *Program in Molecular Medicine, Diabetes Center of Excellence, and Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA; The Jackson Laboratory, Bar Harbor, Maine, USA; and World Class University Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea.
authors.forename: Yongjin
authors.initials: Y
authors.lastname: Lee
authors.affiliation: *Program in Molecular Medicine, Diabetes Center of Excellence, and Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA; The Jackson Laboratory, Bar Harbor, Maine, USA; and World Class University Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea.
authors.forename: Rita
authors.initials: R
authors.lastname: Bortell
authors.affiliation: *Program in Molecular Medicine, Diabetes Center of Excellence, and Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA; The Jackson Laboratory, Bar Harbor, Maine, USA; and World Class University Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea.
authors.forename: Sezin
authors.initials: S
authors.lastname: Dagdeviren
authors.affiliation: *Program in Molecular Medicine, Diabetes Center of Excellence, and Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA; The Jackson Laboratory, Bar Harbor, Maine, USA; and World Class University Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea.
authors.forename: Payal R
authors.initials: PR
authors.lastname: Patel
authors.affiliation: *Program in Molecular Medicine, Diabetes Center of Excellence, and Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA; The Jackson Laboratory, Bar Harbor, Maine, USA; and World Class University Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea.
authors.forename: Xiaodi
authors.initials: X
authors.lastname: Hu
authors.affiliation: *Program in Molecular Medicine, Diabetes Center of Excellence, and Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA; The Jackson Laboratory, Bar Harbor, Maine, USA; and World Class University Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea.
authors.forename: Kunikazu
authors.initials: K
authors.lastname: Inashima
authors.affiliation: *Program in Molecular Medicine, Diabetes Center of Excellence, and Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA; The Jackson Laboratory, Bar Harbor, Maine, USA; and World Class University Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea.
authors.forename: Caitlyn
authors.initials: C
authors.lastname: Kearns
authors.affiliation: *Program in Molecular Medicine, Diabetes Center of Excellence, and Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA; The Jackson Laboratory, Bar Harbor, Maine, USA; and World Class University Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Tsitsilianos
authors.affiliation: *Program in Molecular Medicine, Diabetes Center of Excellence, and Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA; The Jackson Laboratory, Bar Harbor, Maine, USA; and World Class University Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea.
authors.forename: Umber
authors.initials: U
authors.lastname: Shafiq
authors.affiliation: *Program in Molecular Medicine, Diabetes Center of Excellence, and Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA; The Jackson Laboratory, Bar Harbor, Maine, USA; and World Class University Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea.
authors.forename: Leonard D
authors.initials: LD
authors.lastname: Shultz
authors.affiliation: *Program in Molecular Medicine, Diabetes Center of Excellence, and Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA; The Jackson Laboratory, Bar Harbor, Maine, USA; and World Class University Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea.
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Lee
authors.affiliation: *Program in Molecular Medicine, Diabetes Center of Excellence, and Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA; The Jackson Laboratory, Bar Harbor, Maine, USA; and World Class University Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea.
authors.forename: Dale L
authors.initials: DL
authors.lastname: Greiner
authors.affiliation: *Program in Molecular Medicine, Diabetes Center of Excellence, and Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA; The Jackson Laboratory, Bar Harbor, Maine, USA; and World Class University Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea jason.kim@umassmed.edu.
authors.forename: Jason K
authors.initials: JK
authors.lastname: Kim
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology; D059305:Diet, High-Fat / Q000009:adverse effects; D004041:Dietary Fats / Q000009:adverse effects; D004734:Energy Metabolism / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique / Q000379:methods; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D007376:Interleukin-2 / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD / Q000378:metabolism* / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D004041:Dietary Fats; D007328:Insulin; D007376:Interleukin-2; D005947:Glucose
keywords: diabetes mouse models; energy balance; glucose metabolism