Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, 791-0295, Japan.
Sci Rep. 2019 Jan 30;9(1):977. doi: 10.1038/s41598-018-37403-y.
Obesity-induced adipose-tissue dysfunction is a critical contributor to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). B cell-activating factor (BAFF) is an adipokine related to impaired insulin sensitivity, and the serum BAFF concentration is associated with NAFLD severity. In this study, we aimed to determine the direct in vivo role of BAFF in the development of insulin resistance, adipocyte dysfunction, and hepatic steatosis using BAFF mice fed a high-fat diet (HFD). HFD-fed BAFF mice exhibited significantly improved insulin sensitivity despite their increased weight gain and adiposity relative to HFD-fed wild-type mice. Moreover, inflammation, especially the accumulation of CD11c adipose-tissue macrophages, and fibrosis of epididymal adipose tissue were reduced, contributing to healthy adipose-tissue expansion in obese BAFF mice. In line with metabolically healthy obesity, hepatic steatosis also decreased, and we observed attenuated de novo lipogenesis in both the livers and hepatocytes of BAFF mice. Our data revealed that BAFF serves as a potential stimulator of unhealthy adipose-tissue expansion by triggering inflammation and fibrosis and ultimately leading to enhanced insulin resistance and NAFLD. Therefore, these results suggest that BAFF is a promising target for diabetes and NAFLD treatment.
肥胖引起的脂肪组织功能障碍是导致非酒精性脂肪性肝病（NAFLD）发病机制的关键因素。B 细胞激活因子（BAFF）是一种与胰岛素敏感性受损相关的脂肪因子，血清 BAFF 浓度与 NAFLD 严重程度相关。在这项研究中，我们旨在使用高脂肪饮食（HFD）喂养 BAFF 小鼠，确定 BAFF 在胰岛素抵抗、脂肪细胞功能障碍和肝脂肪变性发展中的直接体内作用。与 HFD 喂养的野生型小鼠相比，尽管 HFD 喂养的 BAFF 小鼠体重增加和肥胖程度增加，但它们的胰岛素敏感性显著改善。此外，炎症，特别是 CD11c 脂肪组织巨噬细胞的积累和附睾脂肪组织的纤维化减少，导致肥胖 BAFF 小鼠健康的脂肪组织扩张。符合代谢健康肥胖，肝脂肪变性也减少，我们观察到 BAFF 小鼠的肝脏和肝细胞中新生脂肪生成减弱。我们的数据表明，BAFF 通过触发炎症和纤维化，充当不健康脂肪组织扩张的潜在刺激物，最终导致增强的胰岛素抵抗和 NAFLD。因此，这些结果表明 BAFF 是治疗糖尿病和 NAFLD 的有希望的靶点。
