Saturated and Unsaturated Fatty Acids Differently Modulate Colonic Goblet Cells In Vitro and in Rat Pups

Background: High-fat diets induce intestinal barrier alterations and promote intestinal diseases. Little is known about the effects of long-chain fatty acids (LCFAs) on mucin 2 (MUC2) production by goblet cells, which are crucial for intestinal protection. Objective: We investigated the effects of LCFAs on the differentiation of colonic goblet cells, MUC2 expression, and colonic barrier function. Methods: Upon reaching confluence, human colonic mucus-secreting H129-MTX cells were stimulated (21 d) with a saturated LCFA (palmitic or stearic acid), a monounsaturated LCFA (oleic acid), or a polyunsaturated LCFA (linoleic, gamma-linolenic, alpha-linolenic, or eicosapentaenoic acid). In addition, rat pups underwent oral administration of oil (palm, rapeseed, or sunflower oil) or water (10 mu L/g body weight, postnatal days 10-15). Subsequently, colon goblet cells were studied by Western blotting, reverse transcriptase quantitative polymerase chain reaction, and immunohistochemistry and colonic transmucosal electrical resistance was measured by using Ussing chambers. Results: In vitro, palmitic acid enhanced MUC2 production (140% of control) and hepatocyte nuclear factor 4 alpha expression, whereas oleic, linoleic, gamma-linolenic, alpha-linolenic, and eicosapentaenoic acids reduced MUC2 expression (at least -50% of control). All unsaturated LCFAs decreased the expression of human atonal homolog 1, a transcription factor controlling goblet cell differentiation (at least -31% vs. control). In vivo, rats fed palm oil had higher palmitic acid concentrations (3-fold) in their colonic contents and increased mucus granule surfaces in their goblet cells (>2-fold) than did all other groups. Palm oil also increased colonic transmucosal electrical resistance (245% of control), yet had no effect on occludin and zonula occludens-1 expression. In contrast, sunflower and rapeseed oils decreased goblet cell number when compared with control (at least -10%) and palm oil (at least -14%) groups. Conclusions: Palm oil in rat pups and palmitic acid in HT29-MTX cells increase the production of MUC2 and strengthen the intestinal barrier. In contrast, unsaturated LCFAs decrease MUC2 expression. These data should be taken into account in the context of preventive or therapeutic nutritional programs.