CD28 deletion improves obesity-induced liver steatosis but increases adiposity in mice

International Journal of Obesity : Journal of the International Association for the Study of Obesity
M PoggiJ A Nunès

Abstract

Lymphocytes have a critical role in visceral adipose tissue (AT) inflammation. The CD28 costimulatory molecule is required for lymphocyte activation and for the development of a functional regulatory T cells (Tregs) compartment; however, its role during obesity is unknown. During diet-induced obesity, we investigated the effects of selective interference with CD28 signaling using knockout mice (Cd28KO) and a CTLA4-Ig fusion protein inhibiting CD28-B7 interactions. Cd28 deficiency decreased pathogenic T cells and Treg content within AT without changing the macrophages number. Cd28KO epididymal but not subcutaneous fat was characterized by enlarged adipocytes, reduced levels of inflammatory cytokines and increased Glut4, adiponectin and lipogenic enzyme mRNA levels. This was associated with reduced inflammation, fat accumulation and enhanced glucose metabolism in liver. Weight gain and fasting glucose tolerance were not affected. CTLA4-Ig injections reduced the number of T cells in epididymal AT (epiAT) but not the inflammatory cytokines levels and failed to improve liver fat accumulation. Deletion of CD28 creates a new pro/anti-inflammatory balance in epiAT and liver and exerts a protective effect against hepatic steatosis.

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Citations

Feb 6, 2016·Reviews in Endocrine & Metabolic Disorders·Marina NatiAntonios Chatzigeorgiou
May 27, 2016·Antioxidants & Redox Signaling·Stéphanie O MorinJacques A Nunès
Sep 17, 2020·Obesity Reviews : an Official Journal of the International Association for the Study of Obesity·Lina WangLi Wang
Jan 4, 2017·The Journal of Clinical Investigation·Yukinori Koyama, David A Brenner
Jul 12, 2017·International Journal of Environmental Research and Public Health·Mira HorváthováMartin Gajdoš
Jul 5, 2019·BMC Complementary and Alternative Medicine·Mingzhe ZhuGuang Ji
Nov 22, 2018·Frontiers in Immunology·Qun Wang, Huaizhu Wu

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