1,25-Dihydroxyvitamin D regulates lipid metabolism and glucose utilization in differentiated 3T3-L1 adipocytes

It is well established that adipose tissue can both store and metabolize vitamin D. The active form of vitamin D, 1,25 dihydroxyvitamin D [1,25(OH)(2)D], regulates adipocyte differentiation and inflammation, highlighting the multifaceted role that vitamin D plays in adipose tissue physiology. However, there is limited evidence regarding vitamin D regulation of mature adipocyte lipid metabolism. We hypothesize that 1,25(OH)(2)D alters lipid and glucose metabolism in differentiated 3T3-L1 adipocytes to reduce triacylglycerol (TAG) accumulation. In this study, 1,25(OH)(2)D (10 nmol/L) stimulated a 21% reduction in TAG accumulation in differentiated 3T3-L1 adipocytes after 4 days (P = .01) despite a significant increase in fatty acid uptake (P < .01). Additionally, 1,25(OH)(2)D stimulated a 2.5-fold increase in (CO2)-C-14 production from [1-C-1(4)] palmitic acid (P < .01), indicative of an elevated rate of fatty acid beta-oxidation, while stimulating a 9% reduction in de novo fatty acid synthesis (P = .03). Interestingly, D-[U-C-1(3)]glucose incorporation into fatty acids was reduced by 30% in response to 1,25(OH)(2)D (P < .01), indicating a reduced contribution of glucose as a substrate for de novo lipogenesis. Consistent with these findings, mRNA expression of the anaplerotic enzyme pyruvate carboxylase was reduced by 41% (P < .01). In summary, 1,25(OH)(2)D stimulated fatty acid oxidation and reduced TAG accumulation in differentiated adipocytes. Furthermore, 1,25(OH)(2)D reduced glucose utilization as a substrate for fatty acid synthesis potentially by downregulating pyruvate carboxylase and stimulating glucose disposal as glycerol. Collectively, these 1,25(OH)(2)D-induced changes in lipid metabolism and glucose utilization may contribute to the reduction in TAG accumulation and be protective against excessive fat mass accumulation and associated metabolic disorders. (C) 2018 Elsevier Inc. All rights reserved.