Vitamin D and TNF‐alpha effects on adipogenesis and inflammation in human adipocytes

Abstract

Obesity is associated with meta‐inflammation, a chronic low‐grade inflammatory state with elevated adipose pro‐inflammatory cytokine expression. Elevated TNF‐alpha is a mediator of obesity‐associated insulin resistance. Low vitamin D status is common in obese people, but its inflammatory role in adipocytes is unknown. Our study objective was to determine the effect of 1,25(OH)2D on TNF‐alpha induced changes in adipogenesis and pro‐inflammatory cytokine expression in human primary adipocytes in culture. We differentiated human primary adipocytes in the presence or absence of 1,25(OH)2D and TNF‐alpha and measured lipid accumulation and mRNA expression. We found no effect of 1,25(OH)2D on adipogenesis or proadipogenic gene expression, despite a clear induction of the vitamin D‐responsive gene CYP24 (24‐hydroxylase). Marked inter‐individual differences in 1,25(OH)2D effects on MCP‐1 expression were observed. TNF‐alpha blocked adipogenesis and expression of PPAR‐gamma and C/EBP‐alpha and increased expression of pro‐inflammatory genes IL‐6 and MCP‐1, but not IL‐8. We found no evidence of an interaction between TNF‐alpha and 1,25(OH)2D on adipogenesis or pro‐inflammatory cytokine gene expression. The factors responsible for differential inter‐individual responses of adipocytes to 1,25(OH)2D warrant additional study. Funding source: HATCH MAS00992