Exploration of the metabolic benefits and mechanisms of the flavonoid naringin on lipid homeostasis in high-fat-diet-induced obese mice

Natural flavonoids present safe and effective therapeutic potential for obesity prevention and management. This study elucidates naringin's anti-obesity mechanisms using biochemical, microbiome, and metabolomic analyses in high-fat diet (HFD)-fed mice. Naringin significantly reduced weight gain, adiposity, serum TC/TG levels, hepatic lipid deposition, and adipocyte hypertrophy. It also improved intestinal barrier damage and chronic inflammation, which are closely related to the gut microbiome and its metabolites. Specifically, naringin supplementation modulated the gut microbiota structure, significantly increasing the relative abundance of Lachnospiraceae_NK4A136_group and norank_f__Muribaculaceae , and decreased the relative abundance of norank_f__Desulfovibrionaceae . Simultaneously, naringin supplementation regulated the levels of gut microbiota metabolites, increasing SCFA levels and improving intestinal barrier damage by decreasing serum LPS and D-lactate levels. Mechanistically, naringin activated the PPARα/CPT-1α pathway in the liver, promoting fatty acid oxidation while inhibiting lipid synthesis (SREBP-1c/FASN). In adipose tissue, it activated the AMPK/PGC-1α pathway, inducing white adipose tissue browning (UCP1) and energy expenditure. Untargeted metabolomics further revealed naringin's regulation of cholesterol-bile acid and tryptophan metabolism pathways. Collectively, these findings highlight naringin's multi-targeted potential for treating obesity and metabolic disorders.