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

Abstract

Our previous studies demonstrated that peroxisome proliferator-activated receptor α (PPARα) 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 PPARα. 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 β-cell area in obese mice. ALS-L1023 decreased hepatic lipid accumulation and concomitantly increased the expression of PPARα target genes responsible for fatty acid β-oxidation in livers. In accordance with the in vivo data, ALS-L1023 reduced lipid accumulation and stimulated PPARα reporter gene expression in HepG2 cells. These effects of ALS-L1023 were comparable to those of the PPARα ligand fenofibrate, while the PPARα antagonist GW6471 inhibited the actions of ALS-L1023 on lipid accumulation and PPARα 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 PPARα activation.

Lemon Balm and Corn Silk Extracts Mitigate High-Fat Diet-Induced Obesity in Mice

“…On the contrary, PPARγ facilitates preadipocytes maturation (e.g., C/EBPs) and lipogenesis (e.g., SREBP-1) in the adipose tissue [ 23 , 24 ]. Interestingly, studies from in vitro ligand binding assay and reporter gene assay, harboring PPAR response element, indicated that LBE is capable of binding and transactivating three canonical PPARs [ 12 , 60 ]. In addition, it has been reported that the inhibition of triglyceride accumulation by treatment of lemon balm extract was blocked by pretreatment with GW6471 (a PPARα antagonist) [ 12 ].…”

“…Interestingly, studies from in vitro ligand binding assay and reporter gene assay, harboring PPAR response element, indicated that LBE is capable of binding and transactivating three canonical PPARs [ 12 , 60 ]. In addition, it has been reported that the inhibition of triglyceride accumulation by treatment of lemon balm extract was blocked by pretreatment with GW6471 (a PPARα antagonist) [ 12 ]. Therefore, present results showing 1:1, 1:2, 2:1, and 4:1 ratios of M-LB/CS prevented the altered expression of PPARs mRNA in response to HFD imply that M-LB/CS may regulate adipocyte hypertrophy and obesity primarily through modulating PPARs.…”

“…Modern pharmacological studies using lemon balm and corn silk have been identified a variety of bioactive phytochemicals (e.g., flavonoids, terpenoids, and alkaloids) responsible for their beneficial effects, such as antioxidant and anti-inflammatory activities [ 8 , 10 ]. Moreover, studies have suggested that lemon balm and corn silk are potential herbs for preventing obesity [ 11 , 12 , 13 , 14 , 15 , 16 ]. Furthermore, throughout preliminary screening study from our laboratory, we also found that lemon balm and corn silk extracts could suppress weight gain in experimental animals fed a high-fat diet (HFD) (data not shown).…”

Euphausia pacifica (North Pacific Krill): Review of Chemical Features and Potential Benefits of 8-HEPE against Metabolic Syndrome, Dyslipidemia, NAFLD, and Atherosclerosis

“…Moreover, it is associated with greater risk of developing blood vessel diseases, such as coronary heart disease and stroke. The activation of hepatic PPARα could ameliorate body weight gain and improve insulin sensitivity in HFD-fed obese mice [33]. Moreover, adipocyte hypertrophy and the functional disorder of adipose tissue, such as reduced adiponectin secretion, have been reported to be associated with obesity [34].…”

Medicines for the Treatment of Obesity

“…The authors also described that gomisin N inhibits adipogenesis and lipogenesis by enhancing fatty acid oxidation and thermogenesis and may have a potential preventive and therapeutic agent to combat obesity. Lee et al [ 11 ] demonstrated that lemon balm extract regulates obesity and improve insulin sensitivity via activation of hepatic peroxisome proliferator-activated receptor α (PPARα) in high-fat diet-fed obese C57BL/6J mice. The authors described that lemon balm extract reduces lipid accumulation and stimulates PPARα reporter gene expression in HepG2 cells.…”