Effect of Selenium-Enriched Donkey Milk on Lipid Metabolism Disorders Induced by a High-Fat Diet

Selenium-enriched donkey milk (Se-DM) is characterized by low fat levels, low casein levels, high antioxidant activity, and high selenium content. To date, the regulatory role of Se-DM in the context of a high-fat diet (HFD) is unclear, prompting this present study to elucidate the potential mechanisms by which it affects the gut microbiota and hepatic lipid metabolism in rats fed a high-fat diet. The effects of Se-DM on fat accumulation and lipid peroxidation in HFD rats were investigated through non-targeted fecal metabolomics, short-chain fatty acid (SCFA) quantification, 16S microbial analysis, and pathological assessments. The results showed that Se-DM enhanced SCFA production by promoting Akkermansia muciniphila (A. muciniphila) proliferation, thereby regulating the AMP-activated protein kinase pathway and ferroptosis. Immunoblotting of hepatic tissues and qPCR analyses confirmed the engagement of the AMP-activated protein kinase cascade, suppression of ferroptosis, and reduction in fatty acid synthesis-related proteins (FASN, CD36, SCD1). Our findings revealed that Se-enriched donkey milk (Se-DM) ameliorated lipid metabolism in rats, providing theoretical support for developing functional foods to treat hyperlipidemia.