Obesity Decreases Hepatic 25-Hydroxylase Activity Causing Low Serum 25-Hydroxyvitamin D.
Level 5 - mechanism / opinion, no new human data
Animal and bench laboratory study with no human data
PubMed 30790351 · doi:10.1002/jbmr.3686
What was done
Female mice aged 6 to 24 weeks were weaned onto either a normal chow diet or a high-fat diet. Hepatic abundance of Cyp2r1 (the primary vitamin D 25-hydroxylase) mRNA was measured using digital droplet quantitative PCR. The authors analyzed the relationship between liver Cyp2r1 mRNA levels, serum 25(OH)D concentrations, and the ratio of circulating 25(OH)D3 to cholecalciferol. Ex vivo enzymatic activity assays on isolated livers were performed to quantify 25(OH)D3 generation.
What was found
Mice fed a high-fat diet had a significant decrease in hepatic Cyp2r1 mRNA compared with lean controls (p < 0.001). Cyp2r1 mRNA levels correlated significantly with serum 25(OH)D (p < 0.01) and with the serum 25(OH)D3 to cholecalciferol ratio (p < 0.0001; linear regression R² = 0.85). In ex vivo liver activity assays, obese mice generated significantly less 25(OH)D3 than lean mice (p < 0.05).
Why it matters
The findings demonstrate that obesity-associated vitamin D deficiency is not solely due to adipose tissue sequestration or volumetric dilution, but involves reduced hepatic 25-hydroxylation via downregulated CYP2R1 expression.
Limits
The study was conducted exclusively in female mice; human clinical confirmation and male cohorts were not reported in the abstract. The abstract does not report the exact sample size (n) for the mouse groups or ex vivo assays.
Cited by
- supports The CYP2R1 gene encodes the enzyme responsible for converting inactive supplemental vitamin D into calcifediol.