<i>Perilipin 3</i> Deficiency Stimulates Thermogenic Beige Adipocytes Through <i>PPARα</i> Activation

Abstract

Beige adipocytes can dissipate energy as heat. Elaborate communication between metabolism and gene expression is important in the regulation of beige adipocytes. Although lipid droplet (LD) binding proteins play important roles in adipose tissue biology, it remains unknown whether <i>perilipin 3</i> (<i>Plin3</i>) is involved in the regulation of beige adipocyte formation and thermogenic activities. In this study, we demonstrate that <i>Plin3</i> ablation stimulates beige adipocytes and thermogenic gene expression in inguinal white adipose tissue (iWAT). Compared with wild-type mice, <i>Plin3</i> knockout mice were cold tolerant and displayed enhanced basal and stimulated lipolysis in iWAT, inducing peroxisome proliferator-activated receptor α (<i>PPARα</i>) activation. In adipocytes, <i>Plin3</i> deficiency promoted <i>PPARα</i> target gene and uncoupling protein 1 expression and multilocular LD formation upon cold stimulus. Moreover, fibroblast growth factor 21 expression and secretion were upregulated, which was attributable to activated <i>PPARα</i> in <i>Plin3</i>-deficient adipocytes. These data suggest that <i>Plin3</i> acts as an intrinsic protective factor preventing futile beige adipocyte formation by limiting lipid metabolism and thermogenic gene expression.