Leptin is an adipokine involved in body weight and food intake regulation whose promoter region presents CpG islands that could be subject to dynamic methylation. This methylation process could be affected by environmental (e.g. diet) or endogenous (e.g., adipocyte differentiation, inflammation, hypoxia) factors, and could influence adipocyte leptin gene expression. The aim of this article was to study whether a high-energy diet may affect leptin gene promoter methylation in rats. A group of eleven male Wistar rats were assigned into two dietary groups, one fed on a control diet for 11 weeks and the other on a high-fat cafeteria diet. Rats fed a high-energy diet become overweight and hyperleptin emic as compared to the controls. DNA isolated from retroperitoneal adipocytes was treated with bisulfite and a distal portion of leptin promoter (from −694 to −372 bp) including 13 CpG sites was amplified by PCR and sequenced. The studied promoter portion was slightly more methylated in the cafeteria-fed animals, which was statistically significant (p<0.05) for one of the CpG sites (located at the position −443). In obese rats, such methy lation was associated to lower circulating leptin levels, suggesting that this position could be important in the regulation of leptin gene expression, probably by being a target sequence of different transcription factors. Our findings reveal, for the first time, that leptin methylation pattern can be influenced by diet-induced obesity, and suggest that epigenetic mechanisms could be involved in obesity by regulating the expression of important epiobesigenic genes.

中文翻译：

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高脂肪饮食诱导的肥胖改变了大鼠瘦素启动子的甲基化模式。

瘦素是一种参与体重和食物摄入调节的脂肪因子，其启动子区域呈现出可能发生动态甲基化的 CpG 岛。这种甲基化过程可能受到环境（例如饮食）或内源性（例如脂肪细胞分化、炎症、缺氧）因素的影响，并可能影响脂肪细胞瘦素基因的表达。本文旨在研究高能量饮食是否会影响大鼠瘦素基因启动子甲基化。一组 11 只雄性 Wistar 大鼠被分配到两个饮食组，一个以对照饮食喂养 11 周，另一个以高脂肪食堂饮食喂养。与对照组相比，喂食高能量饮食的大鼠变得超重和高瘦素血症。从腹膜后脂肪细胞中分离的 DNA 用亚硫酸氢盐处理，瘦素启动子的远端部分（从 -694 到 -372 bp）包括 13 个 CpG 位点，通过 PCR 扩增并测序。研究的启动子部分在自助餐厅喂养的动物中甲基化程度略高，这对于 CpG 位点之一（位于 -443 位点）具有统计学意义（p<0.05）。在肥胖大鼠中，这种甲基化与较低的循环瘦素水平有关，这表明该位置在瘦素基因表达的调节中可能很重要，可能是因为它是不同转录因子的靶序列。我们的研究结果首次表明，瘦素甲基化模式会受到饮食诱导的肥胖的影响，