Vaccinium oldhamii Fruit Inhibits Lipid Accumulation in 3T3-L1 Cells and Diet-Induced Obese Animals.

BACKGROUND/OBJECTIVES: Obesity is a significant global health concern, and the natural bioactive compounds with anti-obesity effects remain challenging. This study aims to examine the anti-obesity effect and the potential mechanism of Vaccinium oldhamii fruit water extract (VOW). METHODS: Lipid accumulation, AMP-activated protein kinase (AMPK) activity, and Wnt/β-catenin signaling were evaluated in 3T3-L1 cells. In high-fat and high-sucrose diet (HFHSD)-induced obese mice, body weight, food intake, fat weight, serum lipid profiles, and adipogenic transcription factors were assessed. The most effective VOW fraction was selected by Oil Red O (ORO) staining and its mechanism was studied in 3T3-L1 cells. RESULTS: VOW treatment significantly inhibited cellular lipid accumulation and suppressed phosphorylation of AMPK and its downstream protein, acetyl-CoA carboxylase (ACC). VOW also decreased adipogenic-associated protein expressions such as the peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer-binding proteins α (C/EBP α), sterol regulatory element binding protein-1c (SREBP-1c), and fatty acid synthase (FAS). The enhanced effect of VOW was abolished by the knockdown of AMPK with siRNA. The inhibitory effect of VOW on differentiation depended on the treatment period, even though VOW treatment downregulated the C/EBP β expression at the early phase of differentiation. VOW dramatically reduced activation of AMPK, thereby downregulating adipogenic-associated proteins. Furthermore, the butanol fraction (BtOH) of VOW showed the most powerful effect of VOW dose-dependently reduced lipid accumulation by suppressing the phosphorylation of AMPK. Consistent with inhibited lipid accumulation in vitro, VOW reduced body weight and white adipose tissue weight in the HFHSD-induced obese animal model. CONCLUSIONS: Overall, our study suggested that the anti-adipogenesis effect of VOW and its BtOH fraction involved the activation of AMPK.