Bérengère Benoit1, Jérémie Bruno1, Fanny Kayal1, Monique Estienne2, Cyrille Debard3, Robert Ducroc4, Pascale Plaisancié5. 1. Lyon University, Villeurbanne, France; National Institute of Applied Sciences-Lyon, Pluridisciplinary Institute of Lipid Biochemistry, Villeurbanne, France; 2. National Institute of Applied Sciences-Lyon, Pluridisciplinary Institute of Lipid Biochemistry, Villeurbanne, France; National Institute of Agronomic Research, Research Unit 1397, French Institute of Health and Medical Research U1060, Cardiovascular, Metabolism, Diabetology and Nutrition Laboratory, Villeurbanne, France; 3. National Institute of Agronomic Research, Research Unit 1397, French Institute of Health and Medical Research U1060, Cardiovascular, Metabolism, Diabetology and Nutrition Laboratory, Villeurbanne, France; French Institute of Health and Medical Research U1060, Cardiovascular, Metabolism, Diabetology and Nutrition Laboratory, Oullins, France; and. 4. French Institute of Health and Medical Research U773, Bichat Beaujon Biomedical Research Centre, Paris, France. 5. National Institute of Applied Sciences-Lyon, Pluridisciplinary Institute of Lipid Biochemistry, Villeurbanne, France; National Institute of Agronomic Research, Research Unit 1397, French Institute of Health and Medical Research U1060, Cardiovascular, Metabolism, Diabetology and Nutrition Laboratory, Villeurbanne, France; pascale.plaisancie@inserm.fr.
Abstract
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 HT29-MTX cells were stimulated (21 d) with a saturated LCFA (palmitic or stearic acid), a monounsaturated LCFA (oleic acid), or a polyunsaturated LCFA (linoleic, γ-linolenic, α-linolenic, or eicosapentaenoic acid). In addition, rat pups underwent oral administration of oil (palm, rapeseed, or sunflower oil) or water (10 μL/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 4α expression, whereas oleic, linoleic, γ-linolenic, α-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.
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 HT29-MTX cells were stimulated (21 d) with a saturated LCFA (palmitic or stearic acid), a monounsaturated LCFA (oleic acid), or a polyunsaturated LCFA (linoleic, γ-linolenic, α-linolenic, or eicosapentaenoic acid). In addition, rat pups underwent oral administration of oil (palm, rapeseed, or sunfloweroil) or water (10 μL/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 4α expression, whereas oleic, linoleic, γ-linolenic, α-linolenic, and eicosapentaenoic acids reduced MUC2 expression (at least -50% of control). All unsaturated LCFAs decreased the expression of humanatonal 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.
Authors: Reilly T Enos; Kandy T Velázquez; Jamie L McClellan; Taryn L Cranford; Mitzi Nagarkatti; Prakash S Nagarkatti; J Mark Davis; E Angela Murphy Journal: Am J Physiol Gastrointest Liver Physiol Date: 2016-03-31 Impact factor: 4.052