Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands.
Obesity (Silver Spring). 2015 Dec;23(12):2435-44. doi: 10.1002/oby.21309. Epub 2015 Nov 2.
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.
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.
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.
FcRγ-chain deficiency reduces the development of diet-induced obesity, as well as associated AT inflammation and IR at 11 weeks of HFD.
在肥胖症的发展过程中会产生致病性免疫球蛋白，这些免疫球蛋白有助于导致胰岛素抵抗（IR）。然而，这些抗体影响 IR 的机制在很大程度上尚不清楚。本研究通过研究缺乏信号传导和 FcγR 和 FcεRI 细胞表面表达所必需的 γ 亚基的 FcRγ(-/-) 小鼠，研究了 Fc 受体（FcR）是否通过影响 IR 来促进饮食诱导的肥胖和 IR 的发展。
将 FcRγ(-/-) 和野生型（WT）小鼠用高脂肪饮食（HFD）喂养以诱导肥胖。在第 4 周和第 11 周时，测量体重和胰岛素敏感性，并测定脂肪组织（AT）炎症。此外，还测定了肠道甘油三酯（TG）摄取和血浆 TG 清除率，并分析了肠道微生物群落组成。
FcRγ(-/-) 小鼠在 HFD 喂养 11 周后体重增加较少。它们的肥胖程度、脂肪组织炎症和 IR 降低。有趣的是，与 WT 小鼠相比，FcRγ(-/-) 小鼠的瘦体重更高，这与能量消耗增加有关。FcRγ(-/-) 小鼠的肠道 TG 吸收增加，而血浆 TG 清除率不受影响。肠道微生物群落组成差异显著，因此可能促成了观察到的表型。
FcRγ 链缺失可减少饮食诱导的肥胖的发展，以及在 HFD 喂养 11 周时相关的 AT 炎症和 IR。
