Aberration in leptin expression is one of the most frequent features in the onset and progression of obesity, but the underlying mechanisms are still unclear and need to be clarified. This study investigated the effects of the absence of gut microbiota on body weight and the expression and promoter methylation of the leptin. Male C57 BL/6 J germ-free (GF) and conventional (CV) mice (aged 4–5 weeks) were fed either a normal-fat diet (NFD) or a high-fat diet (HFD) for 16 weeks. Six to eight mice from each group, at 15 weeks, were administered exogenous leptin for 7 d. Leptin expression and body weight gain in GF mice were increased by NFD with more CpG sites hypermethylated at the leptin promoter, whereas there was no change with HFD, compared with CV mice. Adipose or hepatic expression of genes associated with fat synthesis (Acc1, Fas and Srebp-1c), hydrolysis and oxidation (Atgl, Cpt1a, Cpt1c, Ppar-α and Pgc-1α) was lower, and hypothalamus expression of Pomc and Socs3 was higher in GF mice than levels in CV mice, particularly with NFD feeding. Exogenous leptin reduced body weight in both types of mice, with a greater effect on CV mice with NFD. Adipose Lep-R expression was up-regulated, and hepatic Fas and hypothalamic Socs3 were down-regulated in both types of mice. Expression of fat hydrolysis and oxidative genes (Atgl, Hsl, Cpt1a, Cpt1c, Ppar-α and Pgc-1α) was up-regulated in CV mice. Therefore, the effects of gut microbiota on the leptin expression and body weight were affected by dietary fat intake.

中文翻译：

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肠道菌群对瘦素表达和体重的影响通过高脂饮食减轻小鼠

瘦素表达异常是肥胖发病和进展中最常见的特征之一，但其潜在机制仍不清楚，需要澄清。本研究调查了缺乏肠道微生物群对体重以及瘦素表达和启动子甲基化的影响。给雄性 C57 BL/6 J 无菌 (GF) 和常规 (CV) 小鼠（4-5 周龄）喂食正常脂肪饮食 (NFD) 或高脂肪饮食 (HFD) 16 周。每组 6 到 8 只小鼠，在 15 周时，给予外源性瘦素 7 天。NFD 增加了 GF 小鼠的瘦素表达和体重增加，瘦素启动子处有更多的 CpG 位点高甲基化，而与 CV 小鼠相比，HFD 没有变化。脂肪合成相关基因的脂肪或肝脏表达（ACC1,法斯和Srebp-1c)、水解和氧化 (总成,cpt1a,cpt1c,Ppar-α和Pgc-1α) 较低，下丘脑表达聚甲醛和系统3GF 小鼠的水平高于 CV 小鼠的水平，特别是在 NFD 喂养时。外源性瘦素降低了两种类型小鼠的体重，对患有 NFD 的 CV 小鼠的影响更大。脂肪Lep-R表达上调，肝法斯和下丘脑系统3在两种类型的小鼠中均下调。脂肪水解和氧化基因的表达（总成,高速缓存,cpt1a,cpt1c,Ppar-α和Pgc-1α) 在 CV 小鼠中上调。因此，肠道菌群对瘦素表达和体重的影响受到膳食脂肪摄入的影响。