α-Linolenic Acid Alleviated Intestinal Inflammation and Dyshomeostasis Induced by Obesity in Mice

Obesity and its associated metabolic disorders are closely linked to high-fat diet (HFD)-induced intestinal inflammation. In this study, we used an HFD-induced obese mice model to evaluate the regulatory effects of low-dose, medium-dose (M-LA), and high-dose of α-linolenic acid (ALA) on intestinal inflammation and dyshomeostasis. After ALA intervention, all dose groups significantly reduced body weight. Especially M-LA significantly improved serum/hepatic lipid profiles and intestinal histopathology. Furthermore, M-LA significantly upregulated the expression of tight junction proteins and mucin 2, restored goblet cell numbers, and rebalanced the TH17/Treg cell ratio. M-LA decreased the Firmicutes/Bacteroidetes ratio in HFD-fed mice. Additionally, it attenuated hyperproliferation of intestinal stem cells and promoted their differentiation into enteroendocrine cells and goblet cells. We verified its effects on the TLR4/NFκB pathway in both obese mice and LPS-induced Caco-2 cells. The intervention effect of ALA was dose-dependent, with the M-LA (0.221 g/kg) showing the best improvement effect. This study provides a theoretical foundation for dietary active lipids in obesity regulation and the development of ALA-based functional foods.