Saponins from bitter melon reduce lipid accumulation via induction of autophagy in C. elegans and HepG2 cell line

ABSTRACT: Saponins from bitter melon (BMS) are well-known to have various biological activities, especially in the field of fat-lowering. However, many gaps remain in our knowledge of BMS-induced fat reduction and health benefits. Here, we aimed to investigate the precise mechanism of BMS in alleviating fat accumulation in C. elegans and HepG2 cell line. Results indicated that BMS showed strong fat-lowering and lifespan-extension properties. Lipidomic analysis illustrated that BMS could alter the lipid profile, especially represented by phosphatidylethanolamine (PE) increase, which plays an essential role in autophagy. Furthermore, we applied gene-deficient mutants and RNAi technology to confirm that BMS largely depended on daf-16/FoxO1 and hlh-30/TFEB mediated lipophagy to reduce fat deposition. In addition, BMS could ameliorate oil acid (OA)-induced fat accumulation in HepG2 cells by induction of autophagy-related proteins, such as the phosphorylated AMPK and LC3B. In conclusion, our results elucidated the underlying mechanism of bitter melon saponins interfering with lipid metabolism from the autophagy point of view, which provide new insights into a nutraceutical to mitigate obesity. Graphical abstract We aimed to investigate the precise mechanism of saponins from bitter melon (BMS) in alleviating fat accumulation in C. elegans. Results indicated that BMS showed strong fat-lowering and lifespan-extension properties. Lipidomic analysis illustrated that BMS could alter the lipid profile, especially represented by PE increase, which plays an essential role in autophagy. Furthermore, we applied gene-deficient mutants and RNAi technology to confirm that BMS could inhibit fat deposition through daf-16/FoxO1 and hlh-30/TFEB mediated lipophagy. In addition, BMS could ameliorate oil acid (OA)-induced fat accumulation in HepG2 cells by induction of AMPK phosphorylation and LC3B expression, which were involved in autophagy. Thus, we concluded that BMS could ameliorate fat accumulation by inducing autophagy.Image 1 Highlights • Bitter melon saponin (BMS) could inhibit fat accumulation and extended the lifespan of C. elegans.• Lipidomics analysis predicted autophagy may be a key pathway involved in the fat-lowering effects of BMS.• BMS induced daf-16/hlh-30 mediated lipophagy to confer fat-lowering benefit.• BMS regulated autophagy via activating AMPK phosphorylation and LC3B expressions in HepG2 cells.

SUBMITTER: Bai J 

PROVIDER: S-EPMC9352806 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature