Anti-adipogenic Effects of αAL14 Mediated by Modulation of PI3K/Akt Pathways in 3T3-L1 Cells

A model peptide, alpha AL14, was designed from the primary structure of a novel antimicrobial peptide purified form the abalone. alpha AL14 was only reported for antimicrobial and anti-angiogenic effects. Therefore, in this study, we investigated anti-adipogenic effects of alpha AL14 on preadipocyte, 3T3-L1. Obesity is an imbalance in metabolism caused by excessive energy intake or reduced energy consumption, and fat accumulates in the body, which causes chronic disease such as high pressure, cardiovascular disease, diabetes, and cancer. Inhibition of adipogenesis has been focused on as a strategy for treating metabolic disease including diabetes and obesity. In order to confirm the effect on adipocyte differentiation, alpha AL14 was treated while inducing differentiation from preadipocytes into mature adipocytes. We observed that alpha AL14 potently and dose-dependently suppressed accumulation of lipid droplets during mature adipocyte differentiation. alpha AL14 also down-regulated the expression of key adipogenic regulator such as peroxisome proliferator-activated receptor gamma (PPAR gamma), CCAAT/enhancer binding protein alpha (C/EBP alpha) and sterol regulatory element-binding protein 1 (SREBP1). In addition, alpha AL14 diminished the insulin-stimulated phosphoinositide 3-kinase (PI3K)/Akt signaling and its downstream factors that promote adipogenesis by inducing the expression of PPAR gamma, such as mechanistic target of rapamycin (mTOR), glycogen synthase kinase 3 beta (GSK-3 beta) and forkhead box (Fox) transcription factors, which may reduce glucose uptake in response to insulin and lipid accumulation. These results indicated that alpha AL14 suppresses adipocyte differentiation and lipid accumulation depending on multiple mechanisms. In summary, alpha AL14 could be a novel inhibitor of adipogenesis and may have applications for the treatment of obesity.