Regucalcin enhances adipocyte differentiation and attenuates inflammation in 3T3-L1 cells.

Abstract

Dysregulation of adipocyte differentiation and dysfunction play key roles in the pathogenesis of obesity and associated disorders such as diabetes and metabolic syndrome, and as such, a better understanding of the molecular mechanism of adipogenesis may help to elucidate the pathological condition of obesity and its associated disorders. Regucalcin (RGN) plays multiple regulatory roles in intracellular Ca2+ signaling pathways in mammalian cells. Here, we report that overexpression of RGN enhances lipid accumulation in 3T3‐L1 adipocyte cells after adipogenic stimulation, accompanied by upregulation of adipocyte differentiation marker proteins. In contrast, genetic disruption of RGN inhibited adipogenic stimulation‐induced differentiation of 3T3‐L1 cells. Furthermore, RGN overexpression in differentiated 3T3‐L1 adipocytes blocked inflammatory crosstalk between 3T3‐L1 adipocytes and RAW264.7 macrophages in a transwell coculture system. Knockdown of RGN expression in cocultured 3T3‐L1 adipocytes enhanced their susceptibility to RAW264.7 macrophage‐mediated inflammation. These results suggest that RGN is required for 3T3‐L1 adipocyte differentiation and that it exerts anti‐inflammatory activity against 3T3‐L1 adipocyte inflammation after coculture with RAW264.7 macrophages. Thus, RGN may be a novel regulator of adipocyte differentiation and act as a suppressor of inflammation in macrophage‐infiltrated adipocyte tissue.