Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan.
Obesity (Silver Spring). 2011 Oct;19(10):1915-22. doi: 10.1038/oby.2011.165. Epub 2011 Jun 23.
Visceral adipose tissue (VAT) inflammation has been linked to the pathogenesis of insulin resistance and metabolic syndrome. VAT has recently been established as a new component of the immune system and is involved in the production of various adipokines and cytokines. These molecules contribute to inducing and accelerating systemic insulin resistance. In this report, we investigated the role of B cell-activating factor (BAFF) in the induction of insulin resistance. We investigated BAFF levels in the sera and VAT of obese mice. In obese mice, the BAFF levels were preferentially increased in VAT and sera compared to these levels in normal control mice. Next, we treated mice with BAFF to analyze its influence on insulin sensitivity. BAFF impaired insulin sensitivity in normal mice. Finally, we investigated the mechanisms underlying insulin resistance induced by BAFF in adipocytes. BAFF also induced alterations in the expression levels of genes related to insulin resistance in adipocytes. In addition, BAFF directly affected the glucose uptake and phosphorylation of insulin receptor substrate-1 in adipocytes. We propose that autocrine or paracrine BAFF and BAFF-receptor (BAFF-R) interaction in VAT leads to impaired insulin sensitivity via inhibition of insulin signaling pathways and alterations in adipokine production.
内脏脂肪组织（VAT）炎症与胰岛素抵抗和代谢综合征的发病机制有关。VAT 最近被确立为免疫系统的一个新组成部分，参与多种脂肪因子和细胞因子的产生。这些分子有助于诱导和加速全身胰岛素抵抗。在本报告中，我们研究了 B 细胞激活因子（BAFF）在诱导胰岛素抵抗中的作用。我们研究了肥胖小鼠血清和 VAT 中的 BAFF 水平。与正常对照小鼠相比，肥胖小鼠的 VAT 和血清中的 BAFF 水平优先升高。接下来，我们用 BAFF 处理小鼠，分析其对胰岛素敏感性的影响。BAFF 损害了正常小鼠的胰岛素敏感性。最后，我们研究了 BAFF 在脂肪细胞中诱导胰岛素抵抗的机制。BAFF 还诱导了脂肪细胞中与胰岛素抵抗相关基因的表达水平发生变化。此外，BAFF 直接影响脂肪细胞中胰岛素受体底物-1的葡萄糖摄取和磷酸化。我们提出，VAT 中的自分泌或旁分泌 BAFF 和 BAFF 受体（BAFF-R）相互作用通过抑制胰岛素信号通路和改变脂肪因子的产生导致胰岛素敏感性受损。
