Anti-obesity effects of mulberry leaf extracts on female high-fat diet-induced obesity: Modulation of white adipose tissue, gut microbiota, and metabolic markers

Mulberry leaves (MLs) are reported to have beneficial effects in modulating obesity in male models. However, the impact of different types of mulberry leaf extracts (MLEs) on female models, specifically their influence on adipocytes, gut microbiota, and related metabolic markers, remains poorly understood. In this study, we observed a strong correlation between the total phenolic content (TPC), antioxidant and adipocyte modulation effects of water extracted MLEs. HB-W (water-extracted baiyuwang) and HY-W (water-extracted Yueshen) demonstrated remarkable inhibition effects on adipocytes in 3 T3-L1 adipocytes model. Moreover, MLEs effectively reduced the levels of triglycerides (TG), non-esterified fatty acids (NEFA), and total cholesterol (T-CHO) in adipocytes in vitro. In vivo experiments conducted on female mice with high fat diet (HFD)-induced obesity revealed the anti-obesity effects of HB-W and HY-W, leading to a significant decrease in weight gain rates and notable influence on the ratios of adipose tissue, particularly white adipose tissue (WAT). Gene expression analysis demonstrated the up-regulation of WAT-related genes (Pla2g2a and Plac8) by HB-W, while HY-W supplementation showed beneficial effects on the regulation of blood sugar-related genes. Furthermore, both HB-W and HY-W exhibited modulatory effects on obesity-related gut microbiota (Firmicutes-to-Bacteroidetes ratio) and short chain fatty acid (SCFA) contents. Importantly, they also mitigated abnormalities in liver function and uncoupling protein 1 (UPC1) expression. Overall, our findings underscore the anti-obesity effects of MLEs in female rats with high-fat diet-induced obesity.