While activation of beige thermogenesis is a promising approach for treatment of obesity-associated diseases, there are currently no known pharmacological means of inducing beiging in humans. Intermittent fasting is an effective and natural strategy for weight control, but the mechanism for its efficacy is poorly understood. Here, we show that an every-other-day fasting (EODF) regimen selectively stimulates beige fat development within white adipose tissue and dramatically ameliorates obesity, insulin resistance, and hepatic steatosis. EODF treatment results in a shift in the gut microbiota composition leading to elevation of the fermentation products acetate and lactate and to the selective upregulation of monocarboxylate transporter 1 expression in beige cells. Microbiota-depleted mice are resistance to EODF-induced beiging, while transplantation of the microbiota from EODF-treated mice to microbiota-depleted mice activates beiging and improves metabolic homeostasis. These findings provide a new gut-microbiota-driven mechanism for activating adipose tissue browning and treating metabolic diseases.

中文翻译：

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间歇性禁食可通过塑造肠道菌群来促进白色脂肪褐变并减少肥胖。

虽然激活米色热生成是治疗肥胖相关疾病的一种有前途的方法，但目前尚无诱导人乞讨的已知药理方法。间歇性禁食是控制体重的有效且自然的策略，但对其功效的机制了解甚少。在这里，我们显示了隔日禁食（EODF）方案选择性刺激了白色脂肪组织中米色脂肪的生长，并显着改善了肥胖症，胰岛素抵抗和肝脂肪变性。EODF处理导致肠道菌群组成发生变化，从而导致发酵产物乙酸盐和乳酸盐升高，并选择性上调米色细胞中单羧酸盐转运蛋白1的表达。耗竭微生物的小鼠对EODF诱导的拟南芥具有抗性，将微生物群从EODF处理过的小鼠移植到微生物群落枯竭的小鼠中可激活白化作用并改善代谢稳态。这些发现提供了一种新的肠道菌群驱动的机制，用于激活脂肪组织褐变和治疗代谢性疾病。