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Animal Models

Lack of mature lymphocytes results in obese but metabolically healthy mice when fed a high-fat diet

International Journal of Obesity volume 39, pages 1548–1557 (2015)Cite this article

Subjects

Abstract

Background/Objectives:

Obesity is characterized by chronic inflammation and immune dysregulation, as well as insulin resistance, but the link between obesity and adaptive immunity remains to be fully studied.

Methods:

To elucidate the role of adaptive immunity on body composition, glucose homeostasis and inflammation, recombination-activating gene 1 knockout (Rag1−/−) mice, without mature T-lymphocytes or B-lymphocytes, were maintained on a low- or high-fat diet (LFD and HFD, respectively) for 11 weeks.

Results:

Rag1−/− mice fed HFD gained significantly more weight and had increased body fat compared with wild type. Downregulation of energy expenditure as well as brown fat uncoupling protein UCP-1 and UCP-3 gene expression were noticed in HFD-fed Rag1−/− mice compared with LFD. HFD mice had significantly decreased energy intake compared with LFD mice, consistent with decreased agouti-related protein and increased pro-opiomelanocortin gene expression levels in the hypothalamus. Moreover, compared with wild type, Rag1−/− mice had lower interleukin (IL)-4 levels, a cytokine recently found to induce browning in white adipocytes, and higher IL-12 levels in HFD-fed Rag1−/− mice. Despite that HFD Rag1−/− mice were more obese, they had similar glucose, insulin and adiponectin levels, while leptin was marginally increased.

Conclusions:

Mice with deficiency in adaptive immunity are obese, partly owing to decreased energy expenditure, but are metabolically normal, suggesting that mature lymphocytes have necessary roles in the development of obesity-related metabolic dysregulation.

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Acknowledgements

This work was conducted with support from Harvard Catalyst/The Harvard Clinical and Translational Science Center (NIH Award no. UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic health-care centers), a discretionary grant from Beth Israel Deaconess Medical Center and award number 1I01CX000422-01A1 from the Clinical Science Research and Development Service of the VA Office of Research and Development. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health-care centers, the National Center for Research Resources or the National Institutes of Health.

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Authors and Affiliations

  1. Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    X Liu, J Y Huh, H Gong, J P Chamberland, M T Brinkoetter & C S Mantzoros

  2. Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA, USA

    J P Chamberland, O-P R Hamnvik & C S Mantzoros

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  1. X Liu
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Correspondence to C S Mantzoros.

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Liu, X., Huh, J., Gong, H. et al. Lack of mature lymphocytes results in obese but metabolically healthy mice when fed a high-fat diet. Int J Obes 39, 1548–1557 (2015). https://doi.org/10.1038/ijo.2015.93

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