Low serum 25(OH)D concentrations have been reported in obese humans. Inadequate sun exposure and impaired hepatic 25-hydroxylation have been suggested as possible reasons for obesity-associated vitamin D deficiency; however, the underlying mechanism has not been elucidated. We investigated the effects of high fat diet-induced obesity on vitamin D status and vitamin D metabolizing enzyme expression. Male C57BL mice (4 weeks old) were fed control diet containing 10% energy from fat (control group) or high fat diet containing 45% energy from fat (obese group) for 18 weeks. There were no differences in serum 25(OH)D concentrations between two groups, while serum 1,25(OH)2 D concentrations were significantly higher in obese mice. Hepatic mRNA levels of 25-hydroxylases (Cyp2r1, Cyp27a1, and Cyp2j3) were lower in the obese group (31, 30, and 48% lower, respectively). Renal 1α-hydroxylase (Cyp27b1) mRNA levels were higher and 24-hydroxylase (Cyp24) mRNA levels were lower in the obese group. Serum 1,25(OH)2 D concentrations correlated positively with renal Cyp27b1 expression levels and negatively with renal Cyp24 expression levels. Serum PTH concentrations were higher in obese mice. In visceral adipose tissue, Cyp27a1, Cyp2j3, and vitamin D receptor mRNA levels were higher in obese mice. Overall, vitamin D metabolizing enzyme expression was influenced by high fat diet-induced obesity, which might partly explain the mechanisms of the altered vitamin D endocrine system associated with obesity. Higher serum PTH and 1,25(OH)2 D concentrations in obese mice suggest abnormal regulation of serum 1,25(OH)2 D concentrations due to hyperparathyroidism, which might have contributed to lower hepatic 25-hydroxylase mRNA levels.
Vitamin D status has been implicated in obesity and adipose tissue inflammation. In the present study, we explored the effects of dietary vitamin D supplementation on adipose tissue inflammation and immune cell population, and the effects of in vitro 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) treatment on pro-inflammatory cytokine production by stromal vascular cells (SVCs) and adipocytes in lean and high-fat diet-induced obese mice. The results show that epididymal fat Mcp-1 and Rantes mRNA levels, which were higher in obese mice compared with lean mice, were significantly down-regulated by vitamin D supplementation. While obese mice had higher numbers of macrophages and natural killer (NK) cells within adipose tissue, these remained unaltered by vitamin D supplementation. In accordance with these in vivo findings, the in vitro 1,25(OH)2D3 treatment decreased IL-6, MCP-1, and IL-1β production by SVCs from obese mice, but not by adipocytes. In addition, 1,25(OH)2D3 treatment significantly decreased Tlr2 expression and increased mRNA levels of Iκba and Dusp1 in SVCs. These findings suggest that vitamin D supplementation attenuates inflammatory response in adipose tissue, especially in SVCs, possibly through inhibiting NF-κB and MAPK signaling pathways in SVCs but not by the inhibition of macrophage infiltration.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.