Melatonin induces seesaw modulation of glucose and cholesterol homeostasis in 3T3-L1 cells

The effects of melatonin on glucose and lipid metabolism are far from being understood. Although previous studies have found a possible role for melatonin in the regulation of glucose metabolism and cholesterol levels, the underlying mechanisms remain unclear. This study is the first to investigate the effects of melatonin on the expression of several representative markers in glucose and lipid metabolism both in vitro and in vivo. To determine whether reductive effect of melatonin on cell viability of 3T3-L1 preadipocytes was induced by the cytotoxicity of melatonin, a high concentration was administered to primarily cultured neonatal cardiomyocytes. Melatonin did not promote cell death but did result in the differentiation of cardiomyocytes. Additionally, melatonin enhanced marker expression of antioxidants (CAT, SOD and GSR) both in vitro 3T3-L1 preadipocytes and in vivo Sprague-Dawley rats. In 3T3-L1 cells, the mRNA levels of AOEs significantly increased in a concentration-dependent manner (p<0.05) and most of the in vivo studies showed dramatic changes in the rat heart and liver. Significant increases in G6Pase, GCK and HMGCR mRNA levels following melatonin dilution was observed in 3T3-L1 preadipocytes (p<0.05). Moreover, dramatic changes in all three markers were observed in vivo (p<0.05). Taken together, these findings suggest that melatonin may play an important role in glucose and cholesterol homeostasis by modulating the transcription of important enzymes involved in this process. Furthermore, melatonin as an endogenous biological agent could be a potential candidate for clinical therapeutic regimens.