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

Autor: Huizhi Gong, Xiaowen Liu, Joo Young Huh, O-P R Hamnvik, Christos S. Mantzoros, John P. Chamberland, Mary Brinkoetter
Rok vydání: 2015
Předmět:
Zdroj: International Journal of Obesity. 39:1548-1557
ISSN: 1476-5497
0307-0565
DOI: 10.1038/ijo.2015.93
Popis: 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. 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. 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. 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.
Databáze: OpenAIRE