Lemon Balm Extract ALS-L1023 Regulates Obesity and Improves Insulin Sensitivity via Activation of Hepatic PPAR? in High-Fat Diet-Fed Obese C57BL/6J Mice.

ABSTRACT: Our previous studies demonstrated that peroxisome proliferator-activated receptor ? (PPAR?) activation reduces weight gain and improves insulin sensitivity in obese mice. Since excess lipid accumulation in non-adipose tissues is suggested to be responsible for the development of insulin resistance, this study was undertaken to examine whether the lemon balm extract ALS-L1023 regulates hepatic lipid accumulation, obesity, and insulin resistance and to determine whether its mechanism of action involves PPAR?. Administration of ALS-L1023 to high-fat-diet-induced obese mice caused reductions in body weight gain, visceral fat mass, and visceral adipocyte size without changes of food consumption profiles. ALS-L1023 improved hyperglycemia, hyperinsulinemia, glucose and insulin tolerance, and normalized insulin-positive ?-cell area in obese mice. ALS-L1023 decreased hepatic lipid accumulation and concomitantly increased the expression of PPAR? target genes responsible for fatty acid ?-oxidation in livers. In accordance with the in vivo data, ALS-L1023 reduced lipid accumulation and stimulated PPAR? reporter gene expression in HepG2 cells. These effects of ALS-L1023 were comparable to those of the PPAR? ligand fenofibrate, while the PPAR? antagonist GW6471 inhibited the actions of ALS-L1023 on lipid accumulation and PPAR? luciferase activity in HepG2 cells. Higher phosphorylated protein kinase B (pAkt)/Akt ratios and lower expression of gluconeogenesis genes were observed in the livers of ALS-L1023-treated mice. These results indicate that ALS-L1023 may inhibit obesity and improve insulin sensitivity in part through inhibition of hepatic lipid accumulation via hepatic PPAR? activation.

SUBMITTER: Lee D 

PROVIDER: S-EPMC7352304 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature