Abstract

Mannose is an important monosaccharide for protein glycosylation in mammals but is an insignificant cellular energy source. Using a C57BL6/J mouse model of diet-induced obesity, we observed that mannose supplementation of high fat diet-fed mice prevents weight gain, lowers adiposity, reduces liver steatosis, increases maximal O2 consumption, endurance and improves glucose tolerance. Mannose-supplemented mice have higher fecal energy content suggesting reduced caloric absorption by the host. Mannose increases Bacteroidetes to Firmicutes ratio of the gut microbiota, a signature previously associated with the lean phenotype. These beneficial effects of mannose are observed when supplementation is started early in life. Functional transcriptomic analysis of cecal microbiota revealed profound and coherent changes in microbial energy metabolism induced by mannose that are predicted to lead to reduced energy harvest from complex carbohydrates by gut microbiota. Our results suggest that the gut microbiota contributes to mannose-induced resistance to deleterious effects of a high fat diet.

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