1Laboratory of Nutrition, Beijing Pediatric Research Institute,Beijing Children's Hospital,Capital Medical University, National Center for Children's Health,Beijing 100045,People's Republic of China.
2Department of Child Health Care,Beijing Children's Hospital, Capital Medical University,National Center for Children's Health,Beijing 100045,People's Republic of China.
Br J Nutr. 2018 Aug;120(4):385-392. doi: 10.1017/S0007114518001526. Epub 2018 Jun 21.
Specific adipokines, such as adiponectin and resistin, are secreted from adipose tissue and are associated with the development of obesity. Supplementation of dietary SCFA can prevent and reverse high-fat-diet (HFD)-induced obesity. However, it is not clear whether SCFA ameliorate abnormal expression of adiponectin and resistin in the obese state. The aim of this study was to investigate the effects of SCFA on adiponectin and resistin's expressions in diet-induced obese mice, as well as the potential mechanisms associated with DNA methylation. C57BL/6J male mice were fed for 16 weeks with five types of HFD (34·9 % fat by wt., 60 % kJ) - a control HFD and four HFD with acetate (HFD-A), propionate (HFD-P), butyrate (HFD-B) and their admixture (HFD-SCFA). Meanwhile, a low-fat diet (4·3 % fat by wt., 10 % kJ) was used as the control group. The reduced mRNA levels of adiponectin and resistin in the adipose tissue of the HFD-fed mice were significantly reversed by dietary supplementation of acetate, propionate, butyrate or their admixture to the HFD. Moreover, the expressional changes of adiponectin and resistin induced by SCFA were associated with alterations in DNA methylation at their promoters, which was mediated by reducing the expressions of enzyme-catalysed DNA methyltransferase (DNMT1, 3a, 3b) and the methyl-CpG-binding domain protein 2 (MBD2) and suppressing the binding of these enzymes to the promoters of adiponectin and resistin. Our results indicate that SCFA may correct aberrant expressions of adiponectin and resistin in obesity by epigenetic regulation.
特定的脂肪因子，如脂联素和抵抗素，从脂肪组织中分泌出来，与肥胖的发展有关。膳食 SCFA 的补充可以预防和逆转高脂肪饮食（HFD）诱导的肥胖。然而，目前尚不清楚 SCFA 是否能改善肥胖状态下脂联素和抵抗素的异常表达。本研究旨在探讨 SCFA 对饮食诱导肥胖小鼠脂联素和抵抗素表达的影响，以及与 DNA 甲基化相关的潜在机制。C57BL/6J 雄性小鼠用五种 HFD（34.9%脂肪，60%热量）喂养 16 周，包括一种对照 HFD 和四种添加醋酸盐（HFD-A）、丙酸盐（HFD-P）、丁酸盐（HFD-B）及其混合物（HFD-SCFA）的 HFD。同时，低脂饮食（4.3%脂肪，10%热量）作为对照组。饮食补充醋酸盐、丙酸盐、丁酸盐或其混合物到 HFD 中，可显著逆转 HFD 喂养小鼠脂肪组织中脂联素和抵抗素 mRNA 水平的降低。此外，SCFA 诱导的脂联素和抵抗素表达变化与它们启动子上的 DNA 甲基化改变有关，这是通过降低酶催化的 DNA 甲基转移酶（DNMT1、3a、3b）和甲基-CpG 结合域蛋白 2（MBD2）的表达，并抑制这些酶与脂联素和抵抗素启动子的结合来介导的。我们的结果表明，SCFA 可能通过表观遗传调控纠正肥胖中脂联素和抵抗素的异常表达。
