Flavonoids of Rosa sterilis S. D. Shi alleviate high-fat diet-induced hyperlipidemia in mice by activation of autophagy

Obesity and hyperlipidemia are global health crises linked to metabolic disorders, characterized by an abnormal accumulation of triglycerides in fat cells. Autophagy, an essential cellular degradation mechanism, plays a key role in maintaining adipocyte balance and lipid metabolism. Recent studies have found that polysaccharides and the juice of Rosa sterilis S. D. Shi (RS) have hypolipidemic effects. However, the effects of flavonoids from RS (FRS) on lipid metabolism and their potential hypolipidemic and hypoglycemic roles remain unclear. Here, we found that FRS alleviated obesity symptoms and corrected glycolipid metabolism in mice induced by a high-fat diet. Further studies revealed that FRS reduced liver injury and fat accumulation, accompanied by counteracting oxidative stress in the liver of high-fat diet-induced mice. Additionally, FRS inhibited the expression of genes related to fat synthesis and up-regulated the expression of genes related to fat degradation. We also confirmed that FRS significantly influenced lipid metabolism by activating autophagy, promoting lipolysis, and inhibiting adipocyte differentiation. In 3T3-L1 adipocytes, autophagy was suppressed during differentiation, FRS treatment activated autophagy, reduced lipid accumulation, and downregulated adipogenic genes. Blocking autophagy with BAFA1 abolished the effect of FRS. In conclusion, these results suggest that FRS plays a crucial role in lipid metabolism by inhibiting lipid synthesis and increasing autophagy in adipocytes. FRS shows promise as a novel, non-toxic natural product for addressing obesity and hyperlipidemia linked to high-fat diets. Exploring bioactive compounds from natural foods that modulate the autophagy pathway may offer a new therapeutic strategy for treating obesity and hyperlipidemia.