每1
胆固醇7α羟化酶
内分泌学
内科学
昼夜节律
胆汁酸
胆固醇
生物
化学
生物化学
时钟
生物钟
医学
作者
Wenhao Ge,Qi Sun,Yunxia Yang,Zhao Ding,Junhao Liu,Jianfa Zhang
标识
DOI:10.1016/j.jlr.2023.100390
摘要
Several epidemiological studies suggest a correlation between eating time and obesity. Night-eating syndrome characterized by a time-delayed eating pattern is positively associated with obesity in humans as well as in experimental animals. Here we show that oil intake at night significantly makes more fat than that at day in wild type (WT) mice, and circadian Period 1 (Per1) contributes to this day-night difference. Per1-knockout mice are protected from high-fat diet (HFD)-induced obesity, which is accompanied by a reduction in the size of the bile acid pool, and the oral administration of bile acids restores fat absorption and accumulation. We identify that PER1 directly binds to the major hepatic enzymes involved in bile acid synthesis such as cholesterol 7alpha-hydroxylase (CYP7A1) and sterol 12alpha-hydroxylase (CYP8B1). A biosynthesis rhythm of bile acids is accompanied by the activity and instability of bile acid synthases with PER1/PKA-mediated phosphorylation pathways. Both fasting and high fat stress enhance Per1 expression, increasing the fat absorption and accumulation. Our findings reveal that Per1 is an energy regulator and controls daily fat absorption and accumulation.
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