Chronic Effects of a High Sucrose Diet on Murine Gastrointestinal Nutrient Sensor Gene and Protein Expression Levels and Lipid Metabolism

Abstract

The gastrointestinal tract (GIT) plays a key role in regulating nutrient metabolism and appetite responses. This study aimed to identify changes in the GIT that are important in the development of diet related obesity and diabetes. GIT samples were obtained from C57BL/6J male mice chronically fed a control diet or a high sucrose diet (HSD) and analysed for changes in gene, protein and metabolite levels. In HSD mice, GIT expression levels of fat oxidation genes were reduced, and increased de novo lipogenesis was evident in ileum. Gene expression levels of the putative sugar sensor, slc5a4a and slc5a4b, and fat sensor, cd36, were downregulated in the small intestines of HSD mice. In HSD mice, there was also evidence of bacterial overgrowth and a lipopolysaccharide activated inflammatory pathway involving inducible nitric oxide synthase (iNOS). In Caco-2 cells, sucrose significantly increased the expression levels of the nos2, iNOS and nitric oxide (NO) gas levels. In conclusion, sucrose fed induced obesity/diabetes is associated with changes in GI macronutrient sensing, appetite regulation and nutrient metabolism and intestinal microflora. These may be important drivers, and thus therapeutic targets, of diet-related metabolic disease.

Addition of Soluble Fiber in Low-Fat Purified Diets Maintains Cecal and Colonic Morphology, Modulates Bacterial Populations and Predicted Functions, and Improves Glucose Tolerance Compared with Traditional AIN Diets in Male Mice

“…However, our data suggested that the addition of IN was key to maintaining glucose tolerance and both 75CEL25IN and 225CEL25IN groups had similar glucose tolerance compared with those fed the GBD. In addition, replacement of sucrose with glucose-derived carbohydrates may also have benefitted these mice fed 75CEL25IN as sucrose may induce metabolic disease in rats and mice ( 26 , 27 ). While sucrose levels were reduced to 10% in the 93G diet relative to 50% in the 76A diet, it was not completely removed due to pelleting and palatability concerns by the AIN Committee ( 28 ).…”

Addition of soluble fiber in low fat purified diets improves gut and metabolic health compared to traditional AIN diets

“…However, our data suggested that the addition of inulin was key to maintaining glucose tolerance and both OSD groups had similar glucose tolerance compared to those fed the GBD. In addition, replacement of sucrose with glucose derived carbohydrates may also have benefitted these mice fed OSD as sucrose may induce metabolic disease in rats and mice (23,24). While sucrose levels were reduced to 10% in the AIN-93G diet relative to 50% in the AIN-76A diet, it was not completely removed due to pelleting and palatability concerns by the AIN committee (25).…”

Genetic variation in sweet taste receptors and a mechanistic perspective on sweet and fat taste sensation in the context of obesity

“…Martin et al 127 proclaimed that the addition of long‐chain fatty acids (LCFAs) had increased the reinforcement of sucrose in rodents through glucagon‐like peptide‐1 (GLP‐1) release, providing a possible link between fat and sweet taste receptors. Rodents consuming high sucrose diet significantly reduced CD36 expression levels, indirectly implying reduced‐fat sensitivity 128 . The knowledge of obesity would therefore benefit from research on the effect of sweetness on fat sensitivity, both at the receptor level and in the downstream activation of signaling components as well as their crosstalk on cultured TBCs and in animal models.…”

“…Rodents consuming high sucrose diet significantly reduced CD36 expression levels, indirectly implying reduced-fat sensitivity. 128 The knowledge of obesity would therefore benefit from research on the effect of sweetness on fat sensitivity, both at the receptor level and in the downstream activation of signaling components as well as their crosstalk on cultured TBCs and in animal models.…”