Abstract Objective. Continuous exposure to cold leads to an activation of adaptive thermogenesis in the brown adipose tissue and induction of brown/beige cell phenotype in the white adipose tissue. Thermogenic response is associated with alternatively activated macrophages producing catecholamines, which subsequently activate the uncoupling protein 1 (UCP-1). The aim of this work was to elucidate the effect of cold exposure on catecholamine and immune responses associated with adipocyte browning in the mesenteric adipose tissue (mWAT) of rat. Methods. The rats were exposed to continuous cold (4 °C) for 1 or 7 days. Catecholamines production and gene expressions of inflammatory and other factors, related to adipocyte “browning”, were analyzed in the homogenized mWAT samples using 2-CAT ELISA kits. Results. Cold exposure induced a sympathetic response in the mWAT, evidenced by the tyrosine hydroxylase (TH) protein level rise. Induction of non-sympathetical catecholamine production was observed 7 days after cold exposure by elevated TH and phenylethanolamine-N-methyltransferase (PNMT) expression, leading to an increased epinephrine levels. Cold exposure for 7 days stimulated the infiltration of macrophages, evaluated by F4/80 and CD68 expressions, and expression of anti-inflammatory mediators, while pro-inflammatory cytokines were inhibited. Anti- inflammatory response, accompanied by de novo catecholamine production and up-regulation of β3-adrenergic receptors, led to the stimulation of UCP-1 and PGC1α expression, suggesting a cold-induced “browning” of the mWAT, mediated by alternatively activated macrophages. Conclusions. The present data indicate that prolonged cold exposure may induce anti-inflammatory response in mWAT associated with induction of UCP-1 expression. Although functional thermogenesis in the mWAT is most likely redundant, a highly efficient dissipation of energy by UCP1 may affect the energy homeostasis in this visceral fat.
Alternatively activated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis