Trans fatty acids exacerbate dextran sodium sulphate-induced colitis by promoting the up-regulation of macrophage-derived proinflammatory cytokines involved in T helper 17 cell polarization

Abstract

SummaryNumerous reports have shown that a diet containing large amounts of trans fatty acids (TFAs) is a major risk factor for metabolic disorders. Although recent studies have shown that TFAs promote intestinal inflammation, the underlying mechanisms are unknown. In this study, we examined the effects of dietary fat containing TFAs on dextran sodium sulphate (DSS)-induced colitis. C57 BL/6 mice were fed a diet containing 1·3% TFAs (mainly C16:1, C18:1, C18:2, C20:1, C20:2 and C22:1), and then colitis was induced with 1·5% DSS. Colonic damage was assessed, and the mRNA levels of proinflammatory cytokines and major regulators of T cell differentiation were measured. The TFA diet reduced survival and exacerbated histological damage in mice administered DSS compared with those fed a TFA-free diet. The TFA diet significantly elevated interleukin (IL)-6, IL-12p40, IL-23p19 and retinoic acid-related orphan receptor (ROR)γt mRNA levels in the colons of DSS-treated animals. Moreover, IL-17A mRNA levels were elevated significantly by the TFA diet, with or without DSS treatment. We also examined the expression of proinflammatory cytokines in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and peritoneal macrophages. These cells were exposed to TFAs (linoelaidic acid or elaidic acid) with or without LPS and the mRNA levels of various cytokines were measured. IL-23p19 mRNA levels were increased significantly by TFAs in the absence of LPS. Cytokine expression was also higher in LPS-stimulated cells exposed to TFAs than in unexposed LPS-stimulated cells. Collectively, our results suggest that TFAs exacerbate colonic inflammation by promoting Th17 polarization and by up-regulating the expression of proinflammatory cytokines in the inflamed colonic mucosa.

Cross‐generational trans fat intake modifies BDNF mRNA in the hippocampus: Impact on memory loss in a mania animal model

“…As in this experimental group we also observed an increase in RS generation accompanied by an increase in PC levels following AMPH treatment, we hypothesized that: (i) TFA present in neural membranes, even in small amounts, is a precursor of proinflammatory mediators such as cytokines and interleukines (Okada et al, ), favoring RS generation; (ii) AMPH increases dopamine (DA) output from neurons, whose autooxidation also favors RS generation; (iii) Oxidative processes can affect proteins from membranes, as observed by increased PC levels; (iv) Such protein damage seems to have impaired dopamine reuptake, as observed by reduced DAT levels . The reduced reuptake of DA increments DA levels in the synaptic cleft, whose autoxidation generates more pro‐oxidative metabolites; (v) TFA present in membranes may be interfering with DA signaling as well, exacerbating reactive species generation, whose levels were not adequately controlled by the antioxidant defense system; (vi) TFA in neural membranes may affect the synaptic plasticity (Larqué et al, ), modifying neurotransmission; and (v) Taken together, these processes may all be damaging the DNA, as observed by reduced levels of BDNF mRNA, impairing memory performance.…”

The role of diet on intestinal microbiota metabolism: downstream impacts on host immune function and health, and therapeutic implications

“…[113] In contrast, trans-fats appear to exacerbate DSS colitis through up-regulation of Th17 signaling. [114] Unfortunately, the results in human CD patients have been more mixed, with conflicting studies finding that omega-3 fatty acids either decreased the rate of relapse,[115] or had no effect on the remission rate[116]. …”

Molecular Mechanisms for the Modulation of Selected Inflammatory Markers by Dietary Rice Bran Oil in Rats Fed Partially Hydrogenated Vegetable Fat

“…Studies have shown that incorporation of TFA into cell membrane lipids changes the fluidity and associated receptor functions [4]. TFA enriched macrophages secrete high levels of pro-inflammatory interleukins and fibrinogen [5]. The TFA also affect the functions of peroxisome proliferator activated receptor (PPAR)γ [6].…”