High Beta-Palmitate Fat Controls the Intestinal Inflammatory Response and Limits Intestinal Damage in Mucin Muc2 Deficient Mice

Peng Lu,Ingrid B Renes,Anita M Korteland-Van Male,Yael Lifshitz,Fabiana Bar-Yoseph,Liora Levi,Adrianus C J M De Bruijn,Johannes B Van Goudoever,Janneke Witte-Bouma,Jean-Luc Desseyn

doi:10.1371/journal.pone.0065878

Peng Lu, Ingrid B Renes + Show 8 more

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https://doi.org/10.1371/journal.pone.0065878

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Abstract

BackgroundPalmitic-acid esterified to the sn-1,3 positions of the glycerol backbone (alpha, alpha’-palmitate), the predominant palmitate conformation in regular infant formula fat, is poorly absorbed and might cause abdominal discomfort. In contrast, palmitic-acid esterified to the sn-2 position (beta-palmitate), the main palmitate conformation in human milk fat, is well absorbed. The aim of the present study was to examine the influence of high alpha, alpha’-palmitate fat (HAPF) diet and high beta-palmitate fat (HBPF) diet on colitis development in Muc2 deficient (Muc2−/−) mice, a well-described animal model for spontaneous enterocolitis due to the lack of a protective mucus layer.MethodsMuc2−/− mice received AIN-93G reference diet, HAPF diet or HBPF diet for 5 weeks after weaning. Clinical symptoms, intestinal morphology and inflammation in the distal colon were analyzed.ResultsBoth HBPF diet and AIN-93G diet limited the extent of intestinal erosions and morphological damage in Muc2−/− mice compared with HAPF diet. In addition, the immunosuppressive regulatory T (Treg) cell response as demonstrated by the up-regulation of Foxp3, Tgfb1 and Ebi3 gene expression levels was enhanced by HBPF diet compared with AIN-93G and HAPF diets. HBPF diet also increased the gene expression of Pparg and enzymatic antioxidants (Sod1, Sod3 and Gpx1), genes all reported to be involved in promoting an immunosuppressive Treg cell response and to protect against colitis.ConclusionsThis study shows for the first time that HBPF diet limits the intestinal mucosal damage and controls the inflammatory response in Muc2−/− mice by inducing an immunosuppressive Treg cell response.

Highlights

Human milk provides the best nourishment for full-term infants, by which approximately half of the dietary calories are supplied as fat [1]
It has been reported that high beta-palmitate fat (HBPF) rather than high alpha, alpha’palmitate fat (HAPF) enables easy digestion and absorption of fatty acid [6,7,8,9] and calcium [10]
Clinical Symptoms The fats did not affect total food intake as no significant differences among the HAPF, HBPF and AIN-93G groups was observed during the study period (Figure 1A)

Summary

Introduction

Human milk provides the best nourishment for full-term infants, by which approximately half of the dietary calories are supplied as fat [1]. Palmitic acid is predominantly esterified to the sn-2 position of the triglyceride (beta-palmitate) [2]. In vegetable oils, the main constituents of infant formula fat, the palmitic acid is predominantly esterified to the sn-1,3 positions of the triglycerides (alpha, alpha’-palmitate) [3]. Palmitic-acid esterified to the sn-1,3 positions of the glycerol backbone (alpha, alpha’-palmitate), the predominant palmitate conformation in regular infant formula fat, is poorly absorbed and might cause abdominal discomfort. Palmitic-acid esterified to the sn-2 position (beta-palmitate), the main palmitate conformation in human milk fat, is well absorbed. The aim of the present study was to examine the influence of high alpha, alpha’-palmitate fat (HAPF) diet and high beta-palmitate fat (HBPF) diet on colitis development in Muc deficient (Muc22/2) mice, a welldescribed animal model for spontaneous enterocolitis due to the lack of a protective mucus layer

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