Adipochemokines induced by ultraviolet irradiation contribute to impaired fat metabolism in subcutaneous fat cells

Abstract

Background

Adipose tissue is now appreciated as the pivotal regulator of metabolic and endocrine functions. Subcutaneous (SC) fat, in contrast to visceral fat, may protect against metabolic syndrome and systemic inflammation. We demonstrated that chronic as well as acute UV exposure to the skin induces loss of underlying SC fat. UV-irradiated SC fat may produce chemokines or cytokines which modulate lipid homeostasis and secretion of adipokines.

Objectives

We aim to elucidate UV-induced specific adipochemokines implicated in UV-induced modulation of SC fat.

Methods

Primary cultured adipocytes were treated with conditioned media from UV- or sham-irradiated skin cells. Young and old healthy subjects provided SC fat from sun-exposed and sun-protected skin. Another sun-protected skin was irradiated with UV. Differentially expressed adipochemokines were screened by cytokine array, and confirmed in vitro and in vivo. The functions of select adipochemokines involved in lipid metabolism were examined via siRNA-mediated knockdown of cognate receptors.

Results

Specific adipochemokines, including C-X-C chemokines such as ENA-78/CXCL5, and C-C chemokines such as MIP-3α/CCL20 and RANTES/CCL5, were greatly induced in SC fat by UV exposure. They could impair triglyceride synthesis via down-regulation of lipogenic enzymes and sterol regulatory element-binding protein-1 (SREBP-1) through their respective cognate receptors, CXC-chemokine receptor (CXCR)2, CC-chemokine receptor (CCR)6, and CCR5. In addition, UV irradiation induced infiltration of adipose tissue macrophages responsible for the secretion of several chemokines into SC fat.

Conclusions

These UV-induced adipochemokines may be implicated in the reduction of lipogenesis in SC fat, leading to impairment of fat homeostasis and associated comorbidities such as obesity.

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