Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi, China.
Department of Food Science, Cornell University, Ithaca, NY, USA.
Biochim Biophys Acta Mol Basis Dis. 2020 Nov 1;1866(11):165908. doi: 10.1016/j.bbadis.2020.165908. Epub 2020 Jul 31.
Circadian misalignment induced by a high-fat diet (HFD) increases the risk of metabolic diseases. Methionine restriction (MR) is known to have the potential of alleviating obesity by improving insulin sensitivity. However, the role of the circadian clock in mediating the effects of MR on obesity-related metabolic disorders remains unclear. Ten-week-old male C57BL/6 J mice were fed with a low-fat diet (LFD) or a HFD for 4 wk., followed with a full diet (0.86% methionine, w/w) or a methionine-restricted diet (0.17% methionine, w/w) for 8 wk. Our results showed that MR attenuated insulin resistance triggered by HFD, especially at ZT12. Moreover, MR led to a time-specific enhancement of the expression of FGF21 and activated the AMPK/PGC-1α signaling. Notably, MR upregulated the cyclical levels of cholic acid (CA) and chenodeoxycholic acid (CDCA), and downregulated the cyclical level of deoxycholic acid (DCA) in the dark phase. MR restored the HFD-disrupted cyclical fluctuations of lipidolysis genes and BAs synthetic genes and improved the circulating lipid profile. Also, MR improved the expressions of clock-controlled genes (CCGs) in the liver and the brown adipose tissue throughout one day. In conclusion, MR exhibited the lipid-lowering effects on HFD-induced obesity and restored the diurnal metabolism of lipids and BAs, which could be partly explained by improving the expression of CCGs. These findings suggested that MR could be a potential nutritional intervention for attenuating obesity-induced metabolic misalignment.
高脂肪饮食（HFD）引起的昼夜节律失调会增加代谢性疾病的风险。蛋氨酸限制（MR）已被证明通过改善胰岛素敏感性具有减轻肥胖的潜力。然而，生物钟在介导 MR 对肥胖相关代谢紊乱的影响中的作用尚不清楚。将 10 周龄雄性 C57BL/6J 小鼠用低脂饮食（LFD）或 HFD 喂养 4 周，然后用全饮食（0.86%蛋氨酸，w/w）或蛋氨酸限制饮食（0.17%蛋氨酸，w/w）喂养 8 周。我们的结果表明，MR 减轻了 HFD 引起的胰岛素抵抗，尤其是在 ZT12 时。此外，MR 导致 FGF21 的表达在时间上特异性增强，并激活 AMPK/PGC-1α 信号。值得注意的是，MR 上调了胆酸（CA）和鹅去氧胆酸（CDCA）的周期性水平，并下调了脱氧胆酸（DCA）在黑暗阶段的周期性水平。MR 恢复了 HFD 破坏的脂肪分解基因和 BAs 合成基因的周期性波动，并改善了循环脂质谱。此外，MR 改善了肝脏和棕色脂肪组织中时钟控制基因（CCGs）在一天中的表达。总之，MR 对 HFD 诱导的肥胖表现出降脂作用，并恢复了脂质和 BAs 的昼夜代谢，这可以部分解释为改善 CCGs 的表达。这些发现表明，MR 可能是一种潜在的营养干预措施，可减轻肥胖引起的代谢失调。
