Effect of Phyllanthus emblica L. fruit on improving regulation of methylglyoxal-induced insulin resistance in 3T3-L1 cells

Abstract

The increasing methylglyoxal (MG) level of body has been found in people with obesity and insulin resistance, resulting from their dietary style and abnormal metabolic functions. MG promotes inflammation, oxidative stress, glycation, and all of which are closely related to insulin resistance and chronic diseases. Phyllanthus emblica L. fruit has various bioactivities such as anti-inflammation, anti-diabetes, anti-nonalcoholic fatty liver, and anti-dyslipidemia. Therefore, this study was aimed to investigate the effects of water extract of P. emblica (WEPE) and its enriched compound, ellagic acid, on MG-induced inflammation, insulin resistance, and lipogenesis in 3T3-L1 cells. The results showed that MG activated the peroxisome proliferator activated receptor-gamma (PPARγ) and CCAAT/ enhancer-binding protein alpha (C/EBPα), which can increase adipogenesis in adipocytes. In addition, MG enhanced pro-inflammatory cytokine IL-6 protein expression and release through the activation of MAPK and NF-κB signaling pathway, as well as increasing the monocyte chemoattractant protein-1 expression to cause macrophage infiltration. MG also significantly reduced glucose uptake, indicating that insulin resistance in obese patients may be related to MG generation. WEPE and ellagic acid effectively decreased IL-6 protein expression and cytokine release through inactivation of JNK and p65 pathways. WEPE and ellagic acid significantly increased glucose uptake and reduced insulin resistance by MG treatment. WEPE also decreased the protein-tyrosine phosphatase 1B to reduce insulin resistance and inhibited MG-induced fat accumulation related proteins such as PPARγ, C/EBPα, FAS, and p-ACC. Therefore, WEPE may have the potential to ameliorate MG-induced inflammation, increase glucose uptake, and decrease fat accumulation.