Inhibitory effects of kukoamine B on adipogenesis and lipid accumulation in vitro and obesity in vivo

Abstract

Obesity, characterized by excessive adipose tissue accumulation, is an important risk factor for the development of several chronic conditions, including cardiovascular disease, type 2 diabetes mellitus, and hypertension. The present study aimed to investigate the effects of kukoamine B (KB), a major component of the Lycii Radicis Cortex (LRC), on adipogenesis and lipid accumulation in vitro and further assess its role in obesity in vivo. For the in vitro experiments, 3T3-L1 cells and primary-cultured adipose-derived stem cells were used. Lipid accumulation was measured using Oil Red O staining, and adipogenesis-related gene expression was assessed using quantitative reverse transcription polymerase chain reaction. For the in vivo experiments, LRC or KB was orally administered to ovariectomized and high-fat diet-induced obese mice. LRC exhibited antiadipogenic and antiobesity effects in vitro and in vivo experiments. Fractionation of the LRC extract identified KB as a bio-active component. KB treatment resulted in a dose-dependent reduction in lipid droplet formation and downregulation of adipogenesis-related genes, including Pparg, Cebpa, Srebp1, Fasn, and Plin2, in both cell types. Western blot analysis revealed that KB significantly suppressed the protein expression of key adipogenic factors, including phosphorylated CREB, CEBPB, PPARG, and CEBPA. In vivo, KB administration significantly reduced body weight gain, hepatic steatosis, and adipocyte hypertrophy in both mouse models. These results suggest that KB is a potential therapeutic agent for the prevention and treatment of obesity. Further rigorous investigations, including human clinical trials, are necessary to fully elucidate the safety profile, optimal dosing regimens, and long-term effects of KB.