High Fat Diet and High Cholesterol Diet Reduce Hepatic Vitamin D-25-Hydroxylase Expression and Serum 25-Hydroxyvitamin D-3 Level through Elevating Circulating Cholesterol, Glucose, and Insulin Levels
High Fat Diet and High Cholesterol Diet Reduce Hepatic Vitamin D-25-Hydroxylase Expression and Serum 25-Hydroxyvitamin D-3 Level through Elevating Circulating Cholesterol, Glucose, and Insulin Levels
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高脂肪饮食和高胆固醇饮食通过提高循环胆固醇、葡萄糖和胰岛素水平来降低肝脏维生素 D-25-羟化酶表达和血清 25-羟基维生素 D-3 水平
DOI：
10.1002/mnfr.202100220
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发表时间：
2021
影响因子：
5.2
通讯作者：
Le Yingying
中科院分区：
文献类型：
--
作者：
Zhu Tengfei;Zhao Jingyu;Zhuo Shu;Hu Zhimin;Ouyang Shuyu;Wunier;Yu Shuting;Chen Yan;Li Yu;Le Yingying
低循环25 -羟基维生素D （25(OH)D）水平与肥胖、糖尿病和高脂血症有关，但其潜在机制尚不清楚。由于能量密集的饮食会导致这些疾病，本研究调查了饮食是否会损害维生素D的代谢。方法与结果与对照组相比，高脂饮食小鼠血清25(OH) d3和1,25(OH) 2d3水平较低，肝脏维生素D 25 -羟化酶Cyp2r1表达较低，但肾脏维生素D代谢酶表达相近。时间过程研究表明，饲喂HFD后，血清胆固醇、甘油三酯、脂肪酸、葡萄糖、胰岛素浓度依次升高，随后肝脏Cyp2r1表达和血清25(OH) d3水平降低。肝脏Cyp2r1表达在高脂高糖饮食后也会降低。饲喂高胆固醇饲料后，血清总胆固醇升高，肝脏Cyp2r1表达降低，早于血清25(OH)D3的降低。体外研究表明，高浓度的胆固醇、葡萄糖和胰岛素可显著抑制原代小鼠肝细胞中cyp2r1的表达。进一步的研究表明，饮食限制可以改善HFD喂养小鼠的高胆固醇血症、高血糖症和高甘油三酯血症，并提高肝脏Cyp2r1表达和血清25(OH) d3水平。结论：饮食引起的循环胆固醇、葡萄糖和胰岛素升高通过抑制肝脏Cyp2r1表达降低血清25(OH) d3水平。
ScopeLow circulating 25‐hydroxyvitamin D (25(OH)D) levels associate with obesity, diabetes, and hyperlipidemia, but the underlying mechanisms remain uncertain. As energy‐dense diet contributes to these disorders, this study investigates whether diet could impair vitamin D metabolism.Methods and ResultsCompared with control chow‐fed mice, high fat diet (HFD)‐fed mice show lower serum 25(OH)D3and 1,25(OH)2D3levels, lower hepatic vitamin D 25‐hydroxylase Cyp2r1 expression but comparable renal vitamin D metabolic enzymes expression. Time course studies show that after HFD feeding, the serum concentrations of cholesterol, triglycerides, fatty acids, glucose, and insulin elevate sequentially and before the reduction of hepatic Cyp2r1 expression and serum 25(OH)D3levels. Hepatic Cyp2r1 expression also reduces after consuming high fat and high sucrose diet. After high cholesterol diet feeding, serum total cholesterol rises and hepatic Cyp2r1 expression decreases ahead of the reduction of serum 25(OH)D3. In vitro studies demonstrate that high concentrations of cholesterol, glucose, and insulin significantly inhibit Cyp2r1expression in primary murine hepatocytes. Further studies show that dietary restriction in HFD‐fed mice ameliorates hypercholesterolemia, hyperglycemia, and hypertriglyceridemia, and elevates hepatic Cyp2r1 expression and serum 25(OH)D3level.ConclusionThese findings suggest that diet‐induced elevation of circulating cholesterol, glucose, and insulin reduces serum 25(OH)D3level through suppressing hepatic Cyp2r1 expression.