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The effect of mulberry leaf powder and components on preventing obesity and regulating lipid metabolism were investigated in the present study. The mechanism of action was explored by examining the gut microbiota and lipid metabolism-related signaling pathways. As evidenced by the nutritional obesity rats model experiments, the middle concentration mulberry leaf powder (MLP) group (0.8 g/kg⋅d) significantly reduced Lee's index (25.1, compared with model control group [MC] 25.7) and had the strongest lipid metabolism regulation effect. Furthermore, the suppression effects of different mulberry leaf components on nutritional obesity were compared and the mulberry leaf phenolics and fiber mixture (Mulberry leaf mixture [MLM]) group (0.6 g/kg⋅d) was found to have the strongest efficacy (body weight [BW] reduced 12.4%). Real time PCR (RT-qPCR) and western blot analyses demonstrated that MLP (0.8 g/kg⋅d) and its components inhibited adipocyte differentiation and triglyceride synthesis through the PPAR-γ-C/EBP-α signaling pathway, resulting in lipid metabolism regulation. Gut microbiota analysis indicated that MLM (0.6 g/kg⋅d) prevented the reduction in intestinal flora diversity (reach 491 species) caused by highenergy feed, and reduced the Firmicutes/Bacteroidetes ratio (to 7.99%) and the obesity associated flora, Lachnospiraceae (to 19.1%), whereas it improved the content of the beneficial flora, Lactobacilli, Lactobacillus_johnsonii (reach 11.77%).MLM improved the bioaccessibility and bioavailability of the two functional components (phenolics and fiber) and maximized the anti-obesity effect through the gut microbiota-host metabolism pathway. Practical Application: The anti-obesity and lipid metabolism regulation effect of mulberry leaf components were evaluated in this study. The fiber and phenolics of this plant have the potential for development of weight-loss functional foods. K E Y W O R D Sgut microbiota, lipid metabolism, mulberry leaf, obesity INTRODUCTIONObesity has become an important global public health problem that is an enormous burden on both families and entire societies (Liang et al., 2020;Ng, 2014). According to the statistics, by 2030, there will be 2.16 billion overweight and 1.12 billion obese people in the word (Apalasamy & Mohamed, 2015). Excessive body fat results in

Mulberry removed monosaccharides (FM) displayed better hypoglycemic activity than untreated mulberry (MP), which may be attributed the stronger effects of FM on activating PI3K/Akt and AMPK signaling pathways.