High Fat Diet and High Cholesterol Diet Reduce Hepatic Vitamin D‐25‐Hydroxylase Expression and Serum 25‐Hydroxyvitamin D3 Level through Elevating Circulating Cholesterol, Glucose, and Insulin Levels. Issue 21 (4th September 2021)

• Record Type: Journal Article
• Authors: Zhu, Tengfei; Zhao, Jingyu; Zhuo, Shu; Hu, Zhimin; Ouyang, Shuyu; Wunier, ; Yu, Shuting; Chen, Yan; Li, Yu; Le, Yingying
• Is Part Of: Molecular nutrition & food research. Volume 65:Issue 21(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-09-04
• Subjects: diet -- hepatic Cyp2r1 -- hypercholesterolemia -- hyperglycemia -- vitamin D deficiency; Food -- Biotechnology -- Periodicals; Food -- Microbiology -- Periodicals; Nutrition -- Periodicals; Food -- Toxicology -- Periodicals; Nutrition -- Periodicals; Food Microbiology -- Periodicals; Food Technology -- Periodicals; Molecular Biology -- Periodicals; 664.0705
• DOI: 10.1002/mnfr.202100220
• Languages: English
• ISSNs: 1613-4125

Abstract

Abstract : Scope: Low 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 Results: Compared with control chow‐fed mice, high fat diet (HFD)‐fed mice show lower serum 25(OH)D3 and 1, 25(OH)2 D3 levels, 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)D3 levels. 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)D3 level. Conclusion: These findings suggest that diet‐induced elevation of circulating cholesterol, glucose, and insulin reduces serum 25(OH)D3 level through suppressing hepatic Cyp2r1 expression. Abstract : High fat diet‐induced elevation of circulating cholesterol, glucose, and insulin, and high cholesterol diet‐induced elevation of serum cholesterol in mice inhibit vitamin D 25‐hydroxylase Cyp2r1 expression in liver, which results in lower 25(OH)D3 production. Improvement of cholesterol and glucose metabolism through dietary restriction in diet‐induced obese mice contributes to the upregulation of hepatic Cyp2r1 expression and elevation of circulating 25(OH)D3 .