FcRγ‐chain deficiency reduces the development of diet‐induced obesity

• Published in: Obesity (Silver Spring, Md.) Vol. 23; no. 12; pp. 2435 - 2444
• Main Authors: van Beek, Lianne, Vroegrijk, Irene O.C.M., Katiraei, Saeed, Heemskerk, Mattijs M., van Dam, Andrea D., Kooijman, Sander, Rensen, Patrick C.N., Koning, Frits, Verbeek, J. Sjef, Willems van Dijk, Ko, van Harmelen, Vanessa
• Format: Journal Article
• Language: English
• Published: United States 01.12.2015
• Subjects: Adipose Tissue - metabolism; Adiposity - genetics; Animals; Body Weight; Diet, High-Fat - adverse effects; Insulin Resistance - genetics; Male; Mice; Mice, Knockout; Obesity - etiology; Obesity - genetics; Obesity - metabolism; Panniculitis - genetics; Receptors, IgE - metabolism; Receptors, IgG - deficiency; Signal Transduction - genetics; Triglycerides - metabolism
• ISSN: 1930-7381; 1930-739X
• DOI: 10.1002/oby.21309

Objective Pathogenic immunoglobulins are produced during the development of obesity and contribute to the development of insulin resistance (IR). However, the mechanisms by which these antibodies affect IR are largely unknown. This study investigated whether Fc‐receptors contribute to the development of diet‐induced obesity and IR by studying FcRγ−/− mice that lack the γ‐subunit necessary for signaling and cell surface expression of FcγR and FcεRI. Methods FcRγ−/− and wild‐type (WT) mice were fed a high‐fat diet (HFD) to induce obesity. At 4 and 11 weeks, body weight and insulin sensitivity were measured, and adipose tissue (AT) inflammation was determined. Furthermore, intestinal triglyceride (TG) uptake and plasma TG clearance were determined, and gut microbiota composition was analyzed. Results FcRγ−/− mice gained less weight after 11 weeks of HFD. They had reduced adiposity, adipose tissue inflammation, and IR. Interestingly, FcRγ−/− mice had higher lean mass compared to WT mice, which was associated with increased energy expenditure. Intestinal TG absorption was increased whereas plasma TG clearance was not affected in FcRγ−/− mice. Gut microbial composition differed significantly and might therefore have added to the observed phenotype. Conclusions FcRγ‐chain deficiency reduces the development of diet‐induced obesity, as well as associated AT inflammation and IR at 11 weeks of HFD.