Phyllanthus emblica L. extract alleviates leptin resistance and lipid accumulation by inhibiting methylglyoxal production

Increasing leptin resistance and methylglyoxal (MG) levels have been observed in patients with obesity, which is characterized by an imbalance in energy metabolism and abnormal fat accumulation. MG is highly reactive and easily glycates proteins, impairing their physiological functions in cells. Whether MG glycates leptin and results in leptin resistance are untested. Therefore, we hypothesized that MG might directly affect leptin structure and activity or indirectly affect leptin gene and receptor expression, thereby triggering leptin resistance. The fruit of Indian gooseberry (Phyllanthus emblica L.) is rich in phenolic compounds (β-glucogallin, gallic acid, and ellagic acid) and can trap MG. This study aimed to evaluate the effect of a water extract from Indian gooseberry fruit (WEIG) on MG-induced leptin resistance in HepG2 cells. Protein cross-linking and carbonyl content measurement results showed that leptin resistance was induced by MG glycation but improved by WEIG treatment. Moreover, WEIG and its phenolic compounds (gallic acid and ellagic acid) significantly increased the mRNA expression of leptin receptors (Ob-Rb and HuB219.1), and this was accompanied by the suppression of SOCS3 and lipogenesis-associated signaling cascade (SREBP-1/ACC/FAS) gene expression and the activation of the JAK2/STAT3/AMPK/PPAR-α/CPT-1 pathway in human HepG2 liver cells exposed to free fatty acid. In conclusion, WEIG (150 μg/mL) dramatically alleviated leptin resistance and lipid accumulation by MG trapping and inhibiting MG-leptin glycation, indicating that MG is a risk factor for leptin resistance that WEIG can suppress. This finding will increase the application potential of P. emblica L. in anti-obesity functional food industrial development.