UV Modulation of Subcutaneous Fat Metabolism

Abstract

Adipose tissue is not a homogeneous organ. Visceral fat accumulation is associated with atherosclerosis and metabolic syndrome, but peripheral subcutaneous (SC) fat accumulation may be protective. Human skin is continuously exposed to UV light. UV can penetrate the epidermis and into the mid-dermis, but not into the SC fat tissue of human skin. However, we here show that SC fat tissue in chronically sun-damaged skin contains less fat than naturally aged skin, and even a single UV exposure of human skin reduced lipid synthesis in the underlying SC fat tissue through transcriptional regulation of the lipogenic enzymes, acetyl CoA carboxylase, fatty acid synthase, and stearoyl CoA desaturase, of their transcription activator sterol regulatory element-binding protein-1 (SREBP-1), and of two key adipogenic transcription factors, CCAAT/enhancer-binding protein α and peroxisome proliferator-activated receptor γ. The cytokines IL-6, IL-8, monocyte chemoattractant protein-3 (MCP-3), and placenta growth factor, produced by keratinocytes and fibroblasts in response to UV, may be responsible for the reduction of SC fat, and these cytokines, except MCP-3, may act by upregulation of suppressor of cytokine signaling-3 expression. Our data demonstrate the inhibitory effects of UV light on SC lipid synthesis and provide proof of concept for targeting cytokines for SC fat tissue modification.