High‐Fat Diet–Wheat Gluten Interactions in HLA‐DQ8 Transgenic Mice

Unbalanced lipid metabolism contributes to inflammation in several conditions. Gluten, that triggers celiac disease, may also play a role in diseases associated with a high‐fat diet (HFD). Our aim was to investigate the interplay between gluten and HFD in HLA‐DQ8 (DQ8) transgenic mice, a model of gluten sensitivity. DQ8 mice were fed the gluten‐free diet, the HFD, or the HFD containing 8% gluten (HFD + G) for 12 or 23 weeks. Clinical parameters, liver and intestinal histology, immune parameters were assessed. Twelve weeks of HFD increased body and white adipose tissue weight and reduced glucose tolerance in male DQ8 mice. Gluten increased hyperinsulinemia and lipid accumulation in liver; interferon gamma (IFN‐γ) and interleukin‐10 (IL‐10) transcripts were higher in liver of HFD + G‐fed mice. IL‐1β, tumor necrosis factor‐α (TNF‐α), IFN‐γ, and IL‐10 mRNAs increased in the small intestine of HFD + G‐fed mice. However, gliadin‐specific immunity and alterations of the intestinal architecture were not induced. Feeding HFD + G for 23 weeks attenuated the gluten effect. A synergic effect between gluten and HFD after 12 weeks was found, which was instrumental to alter specific metabolic and immune functions in DQ8 mice. These findings provide new insights useful to dissect the association between obesity and gluten sensitivity.