Background: Activation of the thermogenic program in white and brown adipocytes presents a promising avenue for increasing energy expenditure during the treatment of obesity. The endogenous mechanism for promoting thermogenesis in brown adipocytes or browning in white adipocytes has indicated that the gut microbiota is a crucial regulator of the host energy balance. However, whether the effects of the therapeutic intervention-induced modulation of the gut microbiota on adipocyte browning involved the regulation of leptin remains unclear./nMethod: The adipose features were analyzed by body composition analysis, infrared camera observations, transmission electron microscopy and H&E staining. The gene and protein expression in adipose tissue were detected by qRT-PCR, immunoblotting, immunohistochemistry and immunofluorescence staining. The gut microbiome signature was identified by 16S rRNA gene amplicon sequencing, and both mice with high-fat diet-induced obesity (DIO) and mice with antibiotics-induced microbiome depletion were subjected to fecal microbiota transplantation./nResults: Treatment with Panax notoginseng saponins (PNS) shaped the murine gut microbiome by increasing the abundances of Akkermansia muciniphila and Parabacteroides distasonis, and as a result, DIO mice harbored a distal gut microbiota with a significantly increased capacity to reduce host adiposity. The PNS-induced modulation of the gut microbiota in DIO mice could increase brown adipose tissue (BAT) thermogenesis and beige adipocyte reconstruction by activating the leptin-AMPK/STAT3 signaling pathway, which results in the promotion of energy expenditure. Leptin has an essential influence on the anti-obesity effects of PNS. In cases of leptin deficiency, the PNS-induced modulation of the gut microbiota exerts negative effects on thermogenesis and browning in white adipose tissue (WAT), which indicates that PNS fail to reduce obesity in leptin gene-deficient mice. The PNS-induced modulation of the gut microbiota exerted a minimal effect on DIO mice with antibiotic-induced microbiome depletion, which confirmed the correlation between altered gut microbiota and the remodeling of adipose tissues in DIO mice. The direct influence of leptin on browning via the AMPKα/STAT3 signaling pathway in C3H101/2 cells supported our in vivo results that signalling through the leptin-AMPK/STAT3 pathway induced by the PNS-modulated gut microbiota was involved in beige adipocyte reconstruction./nConclusion: Our results revealed that leptin signaling is critical for alterations in microbiota-fat crosstalk and provide promising avenues for therapeutic intervention in the treatment of obesity.

中文翻译：

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三七总皂苷通过瘦素介导的饮食中肥胖引起的瘦素介导的AMPKα/ STAT3信号传导调节肠道微生物群，促进生热和米色脂肪细胞重建

背景：在白色和棕色脂肪细胞中激活产热程序为增加肥胖症治疗期间的能量消耗提供了一条有希望的途径。促进棕色脂肪细胞生热或白色脂肪细胞褐变的内源机制表明，肠道菌群是宿主能量平衡的关键调节剂。然而，无论是在脂肪细胞褐变的肠道菌群的治疗干预引起的调制的影响所涉及的遗体瘦素unclear./n调节方法：通过人体成分分析，红外热像仪观察，透射电子显微镜和H＆E染色来分析脂肪的特征。通过qRT-PCR，免疫印迹，免疫组织化学和免疫荧光染色检测脂肪组织中的基因和蛋白质表达。通过16S rRNA基因扩增子测序鉴定肠道微生物组特征，并对高脂饮食诱导肥胖（DIO）小鼠和抗生素诱导微生物组消耗小鼠进行粪便微生物群移植。/n结果：三七治疗皂苷（PNS）通过增加黏液阿克曼（Akkermansia muciniphila）和副细菌（Parabacteroides distasonis）的丰度来塑造小鼠肠道微生物组因此，DIO小鼠的远端肠道菌群具有明显降低宿主脂肪的能力。PNS诱导的DIO小鼠肠道菌群的调节可通过激活瘦素-AMPK / STAT3信号通路来增加棕色脂肪组织（BAT）的生热和米色脂肪细胞的重建，从而促进能量消耗。瘦素对PNS的抗肥胖作用具有重要影响。在瘦素缺乏的情况下，PNS诱导的肠道微生物群的调节会对白色脂肪组织（WAT）的生热和褐变产生负面影响，这表明PNS无法减轻瘦素基因缺陷小鼠的肥胖。PNS诱导的肠道菌群的调节对抗生素诱导的微生物组耗竭的DIO小鼠影响最小，这证实了DIO小鼠肠道菌群改变与脂肪组织重塑之间的相关性。瘦素对褐变的直接影响通过在C3H101的AMPKα/ STAT3信号传导途径/ 2细胞支持了我们的体内结果，通过由PNS调制肠道菌群诱导瘦素-AMPK / STAT3途径的信号被卷入米色脂肪细胞reconstruction./n结论：我们的结果表明，瘦素信号传导对微生物-脂肪串扰的改变至关重要，并为肥胖症的治疗干预提供了有希望的途径。