Abstract
This study examined the relationship between the high-fat, high-sugar diet (HFHSD) and trinitrobenzene sulfonic acid (TNBS) induced mouse colitis, the therapeutic effect of alpha-linolenic acid (ALA) on mouse colitis, and the relationship between HFHSD and hyperlipidemia. We also examined the possible underlying mechanisms behind their interactions. Female BABL/c mice were fed with HFHSD for the 9 weeks. At the same time, ALA treatment (150 or 300 mg/kg) was administered on a daily basis. At the end of the 9 weeks, experimental colitis was induced by the intra-colonic administration of TNBS. Body weight, spleen weight, disease activity index (DAI), histological changes, T-cell-related cytokine level, and lipid profiles were measured after treatment. TNBS induced severe clinical manifestations of colitis and histological damage. Low-ALA (150 mg/kg) administration profoundly ameliorated TNBS-induced clinical manifestations, body weight loss, spleen weight loss, and histological damage. On the contrary, the high-ALA (300 mg/kg) administration did not ameliorate colitis and even exacerbated the symptoms. HFHSD consumption assisted TNBS in changing IL-12, IFN-γ, IL-2, and IL-17A in the liver. As expected, these changes were recovered through low-ALA. In addition, HFHSD had a significant impact on the total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG), which related to the increased risk of hyperlipidemia. In summation, HFHSD exacerbated the TNBS-induced colitis via the Th1/Th17 pathway. The Low-ALA (150 mg/kg) exhibited protective effects against the TNBS-induced colitis via the Th1/Th2/Th17 pathway.
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Key Points
The remission efficacy of ALA‐rich flaxseed oil for IBD has been well documented, but the effectiveness of purified n‐3 PUFAs pathway primary fatty acid ALA is still less clear. It is worth investigating the effect of modifying n‐6/n‐3 ratio to provide reference to clinic practice. High‐fat, high‐sugar diet (HFHSD) also leads to hyperlipidemia and insulin resistance (IR), which may lead to coronary heart disease (CHD). In the present study, the effects of HFHSD and ALA supplement to trinitrobenzene sulfonic acid (TNBS)‐induced mouse colitis by a dietary intervention strategy, which is consistent with the current popular Western food was investigated. Consuming a low dose of ALA daily significantly prevented the incidence of colitis by the capacity of ALA and its metabolites to adjust the expression of T helper (Th) cell‐related cytokines in the colon. However, over‐increasing n‐3/n‐6 PUFAs ratio did not protect mice from TNBS‐induced colitis and could even exacerbate the symptoms.
In the present study, mice were fed with HFHSD and were supplemented with ALA to balance the n‐3 and n‐6 PUFAs. Consuming a low dose of ALA daily could significantly remit TNBS‐induced colitis in mice via the Th1/Th2/Th17 pathway. However, over‐increasing n‐3/n‐6 PUFAs ratio did not protect mice from TNBS‐induced colitis and could even exacerbate the symptoms. Diets in the current study mimicked 2 g/day (low‐ALA) and 4 g/day (high‐ALA) human ALA consumption. The results suggest that low‐ALA has protective effects against TNBS‐induced colitis via the Th1/Th2/Th17 pathway. The decrease of IL‐17 and the increase of TGF‐β were observed in the high‐ALA (300 mg/kg) group, whereas IL‐2 was not significantly changed in this group. Considering that the balance of the Th17/Treg will shift to Treg cells by signals from IL‐2 and high concentration of TGF‐β, high‐dose ALA might disrupt Th17 pathway in the TNBS‐induced colitis. Furthermore, Treg pathway was not influenced by high‐dose ALA supplement, because no significant difference of IL‐10 was observed. These results support the need to establish a tolerable upper limit for ALA intake, particularly in the context of chronic inflammatory conditions such as IBD.