Endocrine Abstracts

White adipose tissue (WAT) stores excess energy as triglycerides, while brown adipose tissue (BAT) dissipates energy through heat, acting as a defence against cold and obesity and as a positive regulator of metabolic functions. BAT thermogenic functions are mainly induced by mitochondrial uncoupling protein-1 (UCP-1), which induces uptake of lipids and glucose to sustain oxidation and thermogenesis in both brown and beige adipocytes. The ghrelin gene-derived peptides, acylated ghrelin (AG), unacylated ghrelin (UAG) and obestatin (Obe), are key regulators of energy homeostasis, as well as glucose and lipid metabolism. In vivo studies suggest that AG, via the growth hormone (GH) secretagogue receptor type 1a (GHS-R1a), exerts inhibitory effects on UCP-1 mRNA expression and noradrenaline release in BAT; moreover, ablation of GHS-R in mice increased BAT thermogenic functions. However, the role of the ghrelin peptides in adipose browning and BAT function is yet unknown. Thus, we aimed to assess the role of AG, UAG and Obe in promoting white adipocyte browning and on brown adipocyte thermogenic functions. 3T3-L1 preadipocytes and human mesenchymal stem cells (hMSC) were differentiated to white adipocytes for 9 and 21 days respectively. Browning was induced for 72 h with rosiglitazone and insulin, in the presence or absence of AG, UAG and Obe. UAG and Obe, but not AG, increased the mRNA levels of BAT genes (Ucp-1, Cidea, Tmem26, Prdm16, Pgc-1α) and lipolytic genes (CPT-1a and Sirt1), while reducing the lipogenic gene C/EBP in 3T3-L1 and human adipocytes. UAG and Obe also increased the number of small lipid droplets, characteristics of brown adipocytes. The thermogenic role of the peptides will be next studied in rat T37i brown adipocytes. Overall, our findings indicate that Obe and UAG, but not AG may promote browning of adipocytes, leading to the identification of new potential therapeutic targets against obesity and metabolic diseases.