Resveratrol Increases Catecholamine Synthesis in Macrophages: Implications on Obesity

Sympathetic activation of white adipocytes results in the transdifferentiation of white adipocytes into brown like thermogenic adipocytes called beige adipocytes. White adipose tissue (WAT) is composed of several cell types including macrophages and activation of anti-inflammatory M2 macrophages was recently shown to induce beiging of WAT in rodent models. M2 macrophages secrete catecholamines which play a predominant role in the induction of beiging in WAT. In the current study, we demonstrate novel anti-obesity effects of resveratrol (RES), a phytoalexin, mediated through catecholamine synthesis in RAW 264.7 macrophage cell line. RES significantly increased the mRNA expression of tyrosine hydroxylase, phenylalanine N-methyl transferase, dopamine beta hydroxylase and phenyl alanine hydroxylase expression in these cells. In addition, RES increased arginase, a marker for M2 phenotype and decreased LPS-induced iNOS (inducible nitric oxide synthase), a marker for M1 phenotype. Furthermore RES decreased nitric oxide production from LPS-treated RAW264.7 cells. To demonstrate the effect of RES on catecholamine secretion, we examined the cell culture supernatant from RES treated RAW264.7 cells for catecholamine levels. The results indicate that RES significantly increased catecholamine production in LPS-treated RAW264.7 cells. Finally, upregulation of thermogenic markers was seen in mature 3T3-L1 adipocytes incubated with conditioned media from RAW264.7 cells treated with RES. These studies suggest a novel anti-obesity mechanism for RES by increasing catecholamine production in macrophages.Support or Funding InformationThis work was supported by the Biomedical sciences graduate research program at Philadelphia College of Osteopathic Medicine – GA Campus.