High-fat diet reduces CYP2R1 gene needed to make semi-activated vitamin D (mice)

Created August 2021

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

Mol Nutr Food Res. 2021 Aug 27;e2100220. doi: 10.1002/mnfr.202100220 Publisher rents the PDF for $24

Tengfei Zhu 1 2, Jingyu Zhao 1, Shu Zhuo 1, Zhimin Hu 1, Shuyu Ouyang 1, Wunier 1, Shuting Yu 1, Yan Chen 1, Yu Li 1, Yingying Le 1 3

* CYP2R1 (vitamin D 25-hydroxylase ) semiactivates vitamin D in many places in the body * Diabetes and poor Vitamin D genes - many studies * CYP2R1 gene problem increases Multiple Sclerosis risk by 1.4X – Dec 2018 * CYP2R1 mutations also cause vitamin D-deficient rickets – July 2016 * Vitamin D insufficiency was 3.7 X more likely if CYP2R1 gene variation– June 2014 * Lung Cancer (NSLC) more lethal if poor Vitamin D gene ( CYP2R1) – Oct 2019 * Poor CYP2R1 gene reduces blood response to Vitamin D supplementation – Aug 2019 * Response to Vitamin D varied by 12 ng due to gene variants (CYP2R1) – Aug 2019 * GC and CYP2R1 genes associated with higher summer vitamin D levels – Jan 2013 --- One or both of the following causes of low Vitamin D in obese 1. High fat diet ==> lower vitamin D generated * abstract does not indicate strength of this reduction 1. High fat diet ==> increased obesity ==> more vitamin D stored in fatty tissue --- 1. CYP2R1 in Wikipedia CYP2R1 is now known to be regulated, with variations in the expression and activity of CYP2R1 affecting circulating 25(OH)D.[9] Low levels of CYP2R1 activity have been found after 24 hour fasting, in obesity, type 1 and type 2 diabetes[12] and are decreased by glucocorticoids such as dexamethasone.[9] These conditions are known to be linked to low blood levels of 25(OH)D, where even large doses of vitamin D may not produce an improvement, which can be explained by enzyme activities being low.[9] --- Some CYP2R1 studies on web * Diet induced obesity modifies vitamin D metabolism and adipose tissue storage in mice - Jan 2019 FREE PDF * Four days high fat diet modulates vitamin D metabolite levels and enzymes in mice - Jan 2021 $30 * Effects of high fat diet-induced obesity on vitamin D metabolism and tissue distribution in vitamin D deficient or supplemented mice June 2020 FREE PDF * Obesity Represses CYP2R1, the Vitamin D 25-Hydroxylase, in the Liver and Extrahepatic Tissues - July 2020 FREE PDF --- 1. Genetics category listing contains the following {include}

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, we investigated whether diet could impair vitamin D metabolism.

Methods and results: Compared with control chow-fed mice, high fat diet (HFD)-fed mice showed 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 showed that after HFD feeding, the serum concentrations of cholesterol, triglycerides, fatty acids, glucose and insulin elevated sequentially and before the reduction of hepatic Cyp2r1 expression and serum 25(OH)D3 levels. Hepatic Cyp2r1 expression also reduced after consuming high fat and high sucrose diet.

After high cholesterol diet feeding, serum total cholesterol rose and hepatic Cyp2r1 expression decreased ahead of the reduction of serum 25(OH)D3 . In vitro studies demonstrated that high concentrations of cholesterol, glucose and insulin significantly inhibited Cyp2r1 expression in primary murine hepatocytes. Further studies showed that dietary restriction in HFD-fed mice ameliorated hypercholesterolemia, hyperglycemia and hypertriglyceridemia, and elevated hepatic Cyp2r1 expression and serum 25(OH)D3 level.

Conclusion: Our findings suggest that diet-induced elevation of circulating cholesterol, glucose and insulin reduces serum 25(OH)D3 level through suppressing hepatic Cyp2r1 expression.

Tags: Genetics Obesity