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
- Poor CYP2R1 gene results in lower vitamin D and 2X increase in T1 Diabetes – Sept 2019
- 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
- High fat diet ==> lower vitamin D generated
- abstract does not indicate strength of this reduction
- High fat diet ==> increased obesity ==> more vitamin D stored in fatty tissue
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
Genetics category listing contains the following
see also
438 articles in Vitamin D Receptor 153 articles in Vitamin D Binding Protein = GC 43 articles in CYP27B1 - CYP24A1 in title (28 as of May 2022)
- Calcitriol category listing has
54 items - Topical Vitamin D
- Nanoemulsion Vitamin D may be a substantially better form
- CYP3A4
- Getting Vitamin D into your body
Vitamin D blood test misses a lot
- Vitamin D from coming from tissues (vs blood) was speculated to be 50% in 2014, and by 2017 was speculated to be 90%
- Note: Good blood test results (> 40 ng) does not mean that a good amount of Vitamin D actually gets to cells
- A Vitamin D test in cells rather than blood was feasible (2017 personal communication)
- Commercially available 2019
- However test results would vary in each tissue due to multiple genes
- Good clues that Vitamin D is being restricted from getting to the cells
1) A vitamin D-related health problem runs in the family- especially if it is one of 51+ diseases related to Vitamin D Receptor
2) Slightly increasing Vitamin D show benefits (even if conventional Vitamin D test shows an increase)
3) Vitamin D Receptor test (<$30) scores are difficult to understand in 2016- easier to understand the VDR 23andMe test results analyzed by FoundMyFitness in 2018
4) Back Pain- probably want at least 2 clues before taking adding vitamin D, Omega-3, Magnesium, Resveratrol, etc
- The founder of Vitamin D Life took action with clues #3&4
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.
High-fat diet reduces CYP2R1 gene needed to make semi-activated vitamin D (mice) – Aug 2021Printer Friendly PDF this page! Follow this page for updates564 visitors, last modified 28 Aug, 2021,