ScopeAdipose tissue macrophages (ATMs) are crucial in the pathogenesis of insulin resistance (IR). Intermittent fasting (IF) is an effective intervention for obesity. However, the underlying mechanism by which IF improves IR remains unclear.Methods and resultsMale C57BL/6J mice are fed chow‐diet and high‐fat diet (HFD) for 12 weeks, then is randomized into ad libitum feeding or every other day fasting for 8 weeks. Markers of ATMs and expression of uncoupling protein 1 (UCP‐1) are determined. Gut microbiota and bile acids (BAs) are profiled using 16S rRNA sequencing and targeted metabolomics analysis. Results indicate that IF improves IR in HFD‐induced obesity. IF decreases ATM infiltration, pro‐inflammatory M1 gene expression, and promotes white adipose tissue (WAT) browning by elevating UCP‐1 expression. IF restructures microbiota composition, significantly expanding the abundance of Verrucomicrobia particularly Akkermansia muciniphila, with the decrease of that of Firmicutes. IF increases the level of total BAs and alters the composition of BAs with higher proportion of 12α‐hydroxylated (12α‐OH) BAs. The changes in these BAs are correlated with differential bacteria.ConclusionThe findings indicate that IF improves IR partially mediated by the interplay between restructured gut microbiota and BAs metabolism, which has implications for the dietary management in obesity.

中文翻译：

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间歇性禁食通过调节饮食诱导的肥胖症中的肠道微生物群和胆汁酸代谢来改善胰岛素抵抗


范围脂肪组织巨噬细胞 （ATM） 在胰岛素抵抗 （IR） 的发病机制中起关键作用。间歇性禁食 （IF） 是治疗肥胖症的有效干预措施。然而，IF 改善 IR 的潜在机制仍不清楚。方法和结果雄性 C57BL/6J 小鼠喂食食物饮食和高脂饮食 （HFD） 12 周，然后随机进食或每隔一天禁食 8 周。测定 ATM 的标志物和解偶联蛋白 1 （UCP-1） 的表达。使用 16S rRNA 测序和靶向代谢组学分析对肠道微生物群和胆汁酸 （BAs） 进行分析。结果表明，IF 改善了 HFD 诱导的肥胖的 IR。IF 通过提高 UCP-1 表达来减少 ATM 浸润、促炎性 M1 基因表达，并促进白色脂肪组织 （WAT） 褐变。IF 重组微生物群组成，显着扩大了疣微菌门，尤其是嗜粘蛋白阿克曼菌的丰度，而厚壁菌门的丰度有所降低。IF 增加总 BA 的水平并改变 BA 的组成，其中 12α-羟基化 （12α-OH） BA 的比例较高。这些 BA 的变化与差异细菌相关。结论研究结果表明，IF 改善 IR 部分由重组肠道菌群和 BAs 代谢之间的相互作用介导，这对肥胖患者的饮食管理具有影响。