An in vitro study reveals the anti-obesity effects of 7- methoxy-3-methyl-5-((E)-prop-1-enyl)-2-(3,4,5-trimethoxyphenyl)-2,3-dihydrobenzofuran from Myristica fragrans

Abstract

Adipogenesis, the maturation process of preadipocytes, is closely associated with the development of obesity and other complex metabolic syndromes. Herein, we investigated the effect of 7- methoxy-3-methyl-5-((E)- prop-1-enyl)-2-(3,4,5-trimethoxyphenyl)-2,3-dihydrobenzofuran (TM), a benzofuran, isolated from the mace of Myristica fragrans Houtt on adipogenesis in 3T3-L1 preadipocytes to extrapolate whether this compound has any anti-obesity potential. For this, 3T3-L1 preadipocytes were induced to differentiate in the presence of various concentrations of TM (1, 5, 10 μM) and analyzed for triglyceride (TG) accumulation and the expression of proteins and genes involved in lipogenesis and lipolysis associated with adipogenesis. Results showed that TM significantly reduced TG accumulation and expression of marker proteins of adipocyte differentiation (peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein α, and fatty acid-binding protein 4) and increased the secretion of glycerol in a dose-dependent manner. There was a significant dose-dependent decrease in the expression of fatty acid synthase, stearoyl-CoA desaturase-1, sterol regulatory element-binding transcription factor 1c, and acetyl-CoA carboxylase 1 and an increase in carnitine palmitoyltransferase 1, acyl-CoA oxidase, and peroxisome proliferator-activated receptor α in TM treated cells. The phosphorylation of cAMP-activated protein kinase was also increased, which in turn activated the phosphorylation of acetyl-CoA carboxylase in mature adipocytes. Also, there was an increase in glucose uptake by TM, suggesting its insulin-sensitizing potential. This is the first report on the anti-obesity effects of TM from Myristica fragrans on adipogenesis and lipid metabolism in 3T3-L1 adipocytes and demands detailed in vivo study for developing TM as anti-obesity therapeutics.