Glycine enhances expression of adiponectin and IL-10 in 3T3-L1 adipocytes without affecting adipogenesis and lipolysis.

Glycine supplementation has been reported to enhance white-fat loss and improve sensitivity to insulin in animals with obesity or type 2 diabetes. However, the underlying mechanisms responsible for the beneficial effects of glycine remain largely unknown. The purpose of this study was to test the hypothesis that glycine regulates adipocyte differentiation, adipogenesis, and lipolysis, therefore, contributing to white-fat reduction. 3T3-L1 pre-adipocytes were induced to differentiate into adipocytes in the presence of glycine (0, 0.25, 1.0, and 2.0 mmol/L) or resveratrol (50 or 100 μmol/L, served as a positive control) during the differentiation process. Hela and HepG2 cells cultured with oleic acid to induce lipid accumulation in the presence of glycine (0, 1.0, and 2.0 mmol/L) or 10 μmol/L isoproterenol (served as a positive control) for 24 h. Intracellular lipid accumulation, intracellular triglycerides, lipid droplets' diameters of mature adipocytes, mRNA, and protein levels of genes involved in the adipogenesis and lipolysis were analyzed. Isobutylxanthine-dexamethasone-insulin (MDI)-induced adipogenesis in 3T3-L1 cells were blocked by resveratrol, but not by glycine, as shown by decreased lipid contents, reduced diameters of lipid droplets, decreased protein abundances for peroxisome proliferator-activated receptor γ (PPARγ), CCAAT-enhancer-binding protein α (C/EBPα), as well as increased protein abundance of peroxisome proliferator-activated receptor coactivator-1α (PGC-1α), critical transcriptional factors that regulates adipogenesis. However, the mRNA levels of adiponectin and interleukin-10 (IL-10), two adipose-derived adipocytokines with anti-inflammatory effects, were greatly enhanced (P < 0.05) by 2 mmol/L glycine. Compared with non-treated controls, 10 μmol/L isoproterenol significantly decreased (P < 0.05) the intracellular lipid and triglyceride contents induced by oleic acid in Hela and HepG2 cells. mRNA level of fatty acid synthase (FASN), a gene involved in fatty acid synthesis, was significantly reduced (P < 0.05), while that for ATGL (adipose triglyceride lipase) and HSL (hormone-sensitive lipase), genes involved in lipolysis were significantly enhanced (P < 0.05) by isoproterenol. However, oleic acid induced the accumulation of intracellular triglyceride and lipid contents were not affected by glycine. In conclusion, glycine exposure enhanced the mRNA levels of adipose-derived adiponectin and IL-10 without affecting adipogenesis and lipolysis in 3T3-L1 adipocytes. These findings provide a possible explanation for the anti-obesity and anti-diabetic effects of glycine that were previously reported in animal models. More studies are needed to uncover the underlying mechanisms responsible for this regulatory effect of glycine on anti-inflammatory adipocytokines expression in both in vitro and in vivo models.