Jingqing Chen1,2, Yuchen Yang2, Ying Yang2, Zhaolai Dai2, In Ho Kim3, Guoyao Wu4, Zhenlong Wu1,2. 1. Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing, China. 2. State Key Laboratory of Animal Nutrition, Department of Animal Nutrition and Feed Science, China Agricultural University, Beijing, China. 3. Department of Animal Resource & Science, Dankook University, Cheonan, Republic of Korea. 4. Department of Animal Science, Texas A&M University, College Station, TX, USA.
Abstract
BACKGROUND: Obesity, a major public health problem worldwide, is associated with dysfunction of the intestinal barrier. Glycine (Gly) has been reported to enhance the expression of tight-junction proteins in porcine enterocytes. It is unknown whether Gly can improve intestinal barrier integrity in obese mice. OBJECTIVES: This study tested the hypothesis that Gly enhances the intestinal epithelial barrier by regulating endoplasmic reticulum (ER) stress-related signaling and mitigating inflammation in high-fat diet (HFD)-induced obese mice. METHODS: Five-week-old male C57BL/6J mice were fed a normal-fat diet (ND; fat = 10% energy) or an HFD (fat = 60% energy) and received drinking water supplemented with 2% Gly or 2.37% l-alanine (Ala; isonitrogenous control) daily for 12 wk. Body weight gain and tissue weights, glucose tolerance and the activation of immune cells, as well as the abundances of tight-junction proteins, ER stress proteins, and apoptosis-related proteins in the jejunum and colon were determined. In addition, the body weights of naïve ND and HFD groups (nND and nHFD, respectively) were also recorded for comparison. Differences were analyzed statistically by ANOVA followed by the Duncan multiple-comparison test using SAS software. RESULTS: Compared with ND-Ala, HFD-feeding resulted in enhanced macrophage (CD11b+ and F4/80+) infiltration and immune cell activation by 1.9- to 5.4-fold (P < 0.05), as well as the upregulation of ER stress sensor proteins (including phospho-inositol-requiring enzyme 1α and binding immunoglobulin protein) by 2.5- to 4.5-fold, the induction of apoptotic proteins by 1.5- to 3.2-fold, and decreased abundances of tight-junction proteins by 35%-65% (P < 0.05) in the intestine. These HFD-induced abnormalities were significantly ameliorated by Gly supplementation in the HFD-Gly group (P < 0.05). Importantly, Gly supplementation also significantly enhanced glucose tolerance (P < 0.05) by 1.5-fold without affecting the fat accumulation of HFD-induced obese mice. CONCLUSIONS: Gly supplementation enhanced the intestinal barrier and ameliorated inflammation and insulin resistance in HFD-fed mice. These effects of Gly were associated with reduced ER stress-related apoptosis in the intestine of obese mice.
BACKGROUND: Obesity, a major public health problem worldwide, is associated with dysfunction of the intestinal barrier. Glycine (Gly) has been reported to enhance the expression of tight-junction proteins in porcine enterocytes. It is unknown whether Gly can improve intestinal barrier integrity in obese mice. OBJECTIVES: This study tested the hypothesis that Gly enhances the intestinal epithelial barrier by regulating endoplasmic reticulum (ER) stress-related signaling and mitigating inflammation in high-fat diet (HFD)-induced obese mice. METHODS: Five-week-old male C57BL/6J mice were fed a normal-fat diet (ND; fat = 10% energy) or an HFD (fat = 60% energy) and received drinking water supplemented with 2% Gly or 2.37% l-alanine (Ala; isonitrogenous control) daily for 12 wk. Body weight gain and tissue weights, glucose tolerance and the activation of immune cells, as well as the abundances of tight-junction proteins, ER stress proteins, and apoptosis-related proteins in the jejunum and colon were determined. In addition, the body weights of naïve ND and HFD groups (nND and nHFD, respectively) were also recorded for comparison. Differences were analyzed statistically by ANOVA followed by the Duncan multiple-comparison test using SAS software. RESULTS: Compared with ND-Ala, HFD-feeding resulted in enhanced macrophage (CD11b+ and F4/80+) infiltration and immune cell activation by 1.9- to 5.4-fold (P < 0.05), as well as the upregulation of ER stress sensor proteins (including phospho-inositol-requiring enzyme 1α and binding immunoglobulin protein) by 2.5- to 4.5-fold, the induction of apoptotic proteins by 1.5- to 3.2-fold, and decreased abundances of tight-junction proteins by 35%-65% (P < 0.05) in the intestine. These HFD-induced abnormalities were significantly ameliorated by Gly supplementation in the HFD-Gly group (P < 0.05). Importantly, Gly supplementation also significantly enhanced glucose tolerance (P < 0.05) by 1.5-fold without affecting the fat accumulation of HFD-induced obese mice. CONCLUSIONS: Gly supplementation enhanced the intestinal barrier and ameliorated inflammation and insulin resistance in HFD-fed mice. These effects of Gly were associated with reduced ER stress-related apoptosis in the intestine of obese mice.