Department of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan; Amami Laboratory of Injurious Animals, Institute of Medical Science, The University of Tokyo, Japan.
Department of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.
J Nutr Biochem. 2019 Jan;63:177-185. doi: 10.1016/j.jnutbio.2018.10.004. Epub 2018 Oct 11.
Insulin is a key molecule that synchronizes peripheral clocks, such as that in the liver. Although we previously reported that mice fed a low-protein diet showed altered expression of lipid-related genes in the liver and induction of hepatic steatosis, it is unknown whether a low-protein diet impairs insulin secretion and modifies the hepatic circadian rhythm. Therefore, we investigated the effects of the intake of a low-protein diet on the circadian rhythm of insulin secretion and hepatic lipid metabolism in mice. Under 12-h light/12-h dark cycle, mice fed a low-protein diet for 7 days displayed enhanced food intake at the end of the light phase, although central and peripheral PER2 expression rhythm was maintained. Serum insulin levels in mice fed a low-protein diet remained low during the day, and the insulin secretion in OGTT was also markedly lower than in normal mice. In mice fed low-protein diet, hepatic TG accumulation was observed during the nighttime, with relatively high levels of ACC1 mRNA and total ACC proteins. Although there were no differences in the activity rhythm of hepatic mTOR between mice fed a normal or low-protein diet, hepatic IRS-2 expression in mice fed a low-protein diet remained low during the day, with no increase at the beginning of the light period. These results suggested that the low-protein diet eliminated the circadian rhythm of serum insulin and hepatic lipid metabolism in mice, providing insights into our understanding of the mechanisms of hepatic disorders of lipid metabolism.
胰岛素是一种关键分子，它可以同步外周时钟，如肝脏中的时钟。虽然我们之前报道过，低蛋白饮食的小鼠肝脏中脂质相关基因的表达发生改变，并诱导肝脂肪变性，但尚不清楚低蛋白饮食是否会损害胰岛素分泌并改变肝脏的昼夜节律。因此，我们研究了低蛋白饮食对小鼠胰岛素分泌和肝脏脂质代谢昼夜节律的影响。在 12 小时光照/12 小时黑暗周期下，连续 7 天喂食低蛋白饮食的小鼠在光照阶段末期表现出增强的食物摄取，尽管中枢和外周 PER2 表达节律得到维持。低蛋白饮食组小鼠的血清胰岛素水平在白天仍然较低，OGTT 中的胰岛素分泌也明显低于正常小鼠。在低蛋白饮食组的小鼠中，夜间观察到肝 TG 积累，ACC1 mRNA 和总 ACC 蛋白水平相对较高。尽管正常饮食和低蛋白饮食组小鼠的肝 mTOR 活性节律没有差异，但低蛋白饮食组的小鼠肝 IRS-2 表达在白天仍然较低，在光照周期开始时没有增加。这些结果表明，低蛋白饮食消除了小鼠血清胰岛素和肝脏脂质代谢的昼夜节律，为我们理解脂质代谢性肝紊乱的机制提供了新的见解。
