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Front Immunol. 2018 May 28;9:1069. doi: 10.3389/fimmu.2018.01069. eCollection 2018.

Distinct Housing Conditions Reveal a Major Impact of Adaptive Immunity on the Course of Obesity-Induced Type 2 Diabetes.

Author information

1
Department of Endocrinology, Diabetes and Nutrition, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
2
Berlin Institute of Health (BIH), Berlin, Germany.
3
Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
4
Partner Site Berlin, German Centre for Cardiovascular Research (DZHK), Berlin, Germany.
5
Institute of Medical Immunology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
6
Type 1 Diabetes Center, La Jolla Institute for Allergy and Immunology, La Jolla, CA, United States.
7
iPATH Berlin - Core Unit Immunopathology for Experimental Models, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
8
Julius Wolff Institute (JWI), Center for Musculoskeletal Surgery, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.

Abstract

Obesity is associated with adipose tissue inflammation, insulin resistance, and the development of type 2 diabetes (T2D). However, our knowledge is mostly based on conventional murine models and promising preclinical studies rarely translated into successful therapies. There is a growing awareness of the limitations of studies in laboratory mice, housed in abnormally hygienic specific pathogen-free (SPF) conditions, as relevant aspects of the human immune system remain unappreciated. Here, we assessed the impact of housing conditions on adaptive immunity and metabolic disease processes during high-fat diet (HFD). We therefore compared diet-induced obesity in SPF mice with those housed in non-SPF, so-called "antigen exposed" (AE) conditions. Surprisingly, AE mice fed a HFD maintained increased insulin levels to compensate for insulin resistance, which was reflected in islet hyperplasia and improved glucose tolerance compared to SPF mice. By contrast, we observed higher proportions of effector/memory T cell subsets in blood and liver of HFD AE mice accompanied by the development of non-alcoholic steatohepatitis-like liver pathology. Thus, our data demonstrate the impact of housing conditions on metabolic alterations. Studies in AE mice, in which physiological microbial exposure was restored, could provide a tool for revealing therapeutic targets for immune-based interventions for T2D patients.

KEYWORDS:

adaptive immunity; housing conditions; insulin resistance; non-alcoholic steatohepatitis; obesity; type 2 diabetes

PMID:
29892281
PMCID:
PMC5985496
DOI:
10.3389/fimmu.2018.01069
[Indexed for MEDLINE]
Free PMC Article

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