Resveratrol ‐ induced Browning of White Adipose Tissue: Macrophages in the Loop

Abstract

Brown adipose tissue has been a recent target for obesity prevention and therapy. Identification of UCP1‐positive 'beige' adipocytes in the white adipose tissue (WAT) upon exposure to cold led multiple studies to investigate the mechanisms involved in the 'browning' of WAT. Adipose tissue microenvironment is comprised of large number of macrophages in obese than in lean individuals. However, the relative contribution of macrophages to the pathogenesis of obesity is not clearly understood. Recently, the thermogenic beige fat circuitry was identified to contain alternatively activated macrophages (M2‐Macrophages). Furthermore, catecholamine production by M2‐macrophages has been implicated in adaptive thermogenesis. In the current study, we investigated the novel mechanism through which a well‐studied anti‐obesity phytochemical resveratrol (RSV) induces browning of WAT. We observed that RSV significantly increased IL10 secretion; a signature cytokine of M2‐macrophages, at both transcriptional and translational level in LPS‐treated mouse macrophage cell line (RAW264.7). Further, RSV rescued RAW264.7 cells from LPS‐induced cell death. Additionally, RSV induced catecholamine secretion by RAW264.7 cells through upregulation of tyrosine hydroxylase in a time and dose dependent manner. Taken together, these studies suggest that RSV‐induced change in the polarity of macrophages leading to elevated levels of catecholamines will induce browning of WAT and contributes to the anti‐obesity effects of RSV. This work was supported by the CSO Intramural Funds from the Philadelphia College of Osteopathic Medicine ‐ School of Pharmacy.