Effects of Vitamin D Supplementation on 1, 25-dihydroxyvitamin D Metabolism and Its Impact on Adipose Tissue Inflammation in Obese Mice (P24-004-19)

Abstract

Abstract Objectives Adipose tissue expresses CYP27B1 and VDR, suggesting local metabolism and function of 1,25-dihydroxyvitamin D (1,25(OH)2D) in adipose tissue. Obesity has been associated with dysregulation of 1,25(OH)2D levels. We investigated effects of vitamin D supplementation on 1,25(OH)2D metabolism and its impact in adipose tissue of obese mice. Methods Six-wk-old C57BL/6 mice were divided into 4 groups and fed experimental diets containing 10% or 45% kcal fat (CON or HFD) and differing in vitamin D content (1000 or 25,000 IU/kg of diet, DC or DS) for 13 wks. Serum 1,25(OH)2D and PTH levels were determined with radio- or enzyme-immunoassay. The mRNA levels of Cyp27b1, Cyp24a1, and Lrp2 in the kidney, and Cyp27b1, Vdr, and pro-inflammatory cytokines (Mcp-1, Rantes, Mip-1γ, Tnf-α, Il-6, Il-1β, and Ifn-γ) in the epididymal adipose tissue were determined by real-time PCR. Results Overall, serum 1,25(OH)2D levels were higher in DS groups compared with DC groups. When 1,25(OH)2D levels were compared between CON and HFD groups, differential pattern was observed depending on vitamin D levels in the diet. HFD-DC group showed higher serum 1,25(OH)2D and PTH levels compared with CON-DC group. However, in the DS groups, serum 1,25(OH)2D and PTH levels were not significantly affected by dietary fat amount. Renal Cyp24a1 mRNA levels, which could be up-regulated by dietary vitamin D, was higher in CON-DS group compared with CON-DC group. However, in the HFD groups, renal Cyp24a1 mRNA levels were similar in DC and DS groups. Mcp-1 and Rantes mRNA levels were higher in the HFD groups compared with CON groups, and their overall expression levels were down-regulated by vitamin D supplementation. Overall, mRNA levels of Il-6 and Il-1β were lower in the DS groups compared with DC groups. Conclusions Dietary vitamin D supplementation alleviated inflammatory responses in adipose tissue. Both 1,25(OH)2D in circulation and locally produced 1,25(OH)2D in adipose tissue might have contributed to the effect. Funding Sources Supported by the grant from the National Research Foundation (NRF) of Korea (NRF-2018R1D1A1B070491).