Investigation in the pathogenesis of metabolic syndrome with in vivo molecular imaging

已知肥胖会诱导脂肪组织内的局部炎症，从而导致全身代谢异常。我们研究了调节脂肪炎症的潜在机制。我们鉴定了在脂肪组织中组成性产生白细胞介素-10的布雷格细胞。在饮食诱导的肥胖小鼠中，B细胞特异性IL 10缺失增强了脂肪炎症和胰岛素抵抗，而脂肪组织布雷格细胞的过继转移改善了这些效应。脂肪环境因素，包括CXCL 12和游离脂肪酸，支持布雷格细胞功能，以及布雷格细胞分数和功能在来自肥胖小鼠和人的脂肪组织中降低。我们的研究结果表明，脂肪组织布雷格细胞维持脂肪组织内的稳态，并且布雷格细胞功能障碍对肥胖症中脂肪组织炎症的进展起关键作用，并且可能在代谢综合征的发病机制中起重要作用。

Obesity is known to induce local inflammation within adipose tissue that contributes to systemic metabolic abnormalities. We investigated the underlying mechanisms that modulate adipose inflammation. We identified Breg cells that produce interleukin-10 constitutively within adipose tissue. B cell-specific Il10 deletion enhanced adipose inflammation and insulin resistance in diet-induced obese mice, whereas adoptive transfer of adipose tissue Breg cells ameliorated those effects. Adipose environmental factors, including CXCL12 and free fatty acids, support Breg cell function, and Breg cell fraction and function were reduced in adipose tissue from obese mice and humans. Our findings indicate that adipose tissue Breg cells maintain homeostasis within adipose tissue and that Breg cell dysfunction contributes pivotally to the progression of adipose tissue inflammation in obesity and may play significant roles in the pathogenesis of metabolic syndrome.