Diet induced obesity modifies vitamin D metabolism and adipose tissue storage in mice

Abstract

Low circulating levels of total and free 25-hydroxyvitamin D (25(OH)D) indicative of vitamin D status have been associated with obesity in humans. Moreover, obesity is thought to play a causal role in the reduction of 25(OH)D levels, and several theories have been put forward to explain this relationship. Here we tested the hypothesis that obesity disrupts vitamin D homeostasis in key organs of vitamin D metabolism. Male C57BL6 mice were fed for 7 or 11 weeks on either a control diet (control, 10% energy from fat) or a high-fat diet (HF, 60% energy from fat) formulated to provide equivalent vitamin D3 intake in both groups. After 7 weeks, there was a transient increase of total 25(OH)D together with a significant decrease of plasma vitamin D3 that could be related to the induction of hepatic genes involved in 25-hydroxylation. After 11 weeks, there was no change in total 25(OH)D but a significant decrease of free 25(OH)D and plasma vitamin D3 levels. We also quantified an increase of 25(OH)D in adipose tissue that was inversely correlated to the free 25(OH)D. Interestingly, this accumulation of 25(OH)D in adipose tissue was highly correlated to the induction of Cyp2r1, which could actively participate in vitamin D3 trapping and subsequent conversion to 25(OH)D in adipose tissue. Taken together, our data strongly suggest that the enzymes involved in vitamin D metabolism, notably in adipose tissue, are transcriptionally modified under high-fat diet, thus contributing to the obesity-related reduction of free 25(OH)D.

Obesity and Vitamin D Metabolism Modifications

“…Indeed, authors reported that a high fat (HF) diet resulted in modification of CYP2R1 expression (mRNA and protein), leading to a decrease of 25hydroxylase activity in the liver, which could explain the reduced serum 25-hydroxyvitamin D. Such observation is clearly in agreement with recent reports demonstrating that diet-induced obesity leads to modifications on the vitamin D metabolism, in the liver and in adipose tissue of mice, which may explain plasma vitamin D metabolites variations observed during obesity. (2,3) This is also in agreement with human observations. (4) Nevertheless, if the decrease of 25(OH)D is well established in human, even if the origin is still elusive, (4)(5)(6)(7) such assumption is less clear in mice.…”

“…Indeed, when the concentration of cholecalciferol is balanced between control and HF diets, to bring the same amounts of cholecalciferol to mice, taking into account the lowest consumption of HF diet, (8) the decrease of total 25(OH)D is not obvious. (2,3,9) In this context, it is surprising that in their study, Roizen et al (1) did not adjust the quantity of cholecalciferol between groups by increasing the cholecalciferol concentration in the HF diet. At the opposite, the concentration of cholecalciferol was reduced in the HF group (2.1 UI/g) compared with the control group (3.3 UI/g).…”

Vitamin D Supplementation Improves Adipose Tissue Inflammation and Reduces Hepatic Steatosis in Obese C57BL/6J Mice

“…As stated previously, it has recently been reported that obesity in humans reduced the effect of VD supplementation [35]. In the present study, we did not measure adipose tissue concentration of 1,25(OH)2D, but based on our previously reported data [34], we can speculate that this metabolite is present at a lower concentration in obese mice compared with the levels in the NC-fed mice. We can also speculate that the VD supplementation was not sufficient to reach a 1,25(OH)2D concentration able to modulate fatty acid oxidation, which is considered as a major driving force of weight loss [18,36,37].…”

“…However, it is noteworthy that a study, performed on obese mice injected with 1,25(OH)2D reported a limited weight gain compared with control obese mice [33]. Such discrepancy could be due to the impact of diet-induced obesity on VD metabolism [34]; the direct administration of 1,25(OH)2D, could bypass the metabolization of cholecalciferol, and therefore be more efficient. As stated previously, it has recently been reported that obesity in humans reduced the effect of VD supplementation [35].…”

Lower serum 25-hydroxyvitamin D3 concentration is associated with higher pain and disability in subjects with low back pain: a case-control study

“…There was a significant difference in serum concentration of25 hydroxyvitamin D in patients with LBP in comparison to subjects without LBP. The serum concentration of 25 hydroxyvitamin D was significantly lower in patients with LBP and 42.85% and 22.22% of them had vitamin D deficiency and insufficiency, respectively.…”