Supplementation of oligofructose, but not sucralose, decreases high-fat diet induced body weight gain in mice independent of gustducin-mediated gut hormone release

cope Entero-endocrine cells (EECs) sense nutrients through taste receptors similar to those on the tongue. Sweet -and fatty acid taste (FFAR) receptors coupled to the gustatory G-protein, gustducin, on EECs play a role in gut hormone release. We studied if supplementation of artificial (sucralose) or prebiotic (oligofructose; OFS) sweeteners target gustducin-mediated signaling pathways to alter gut hormone release and reduce obesity-associated disorders. Methods and results Wild type (WT) and α-gustducin knockout (α-gust−/−) mice were fed a high-fat diet and gavaged once daily (8 weeks) with water or equisweet concentrations of sweeteners. OFS but not sucralose decreased body weight gain (-19±3%, P<0.01), fat pad mass (-55±6%, P<0.001) and insulin resistance (-39±5%, P<0.001) independent of α-gustducin. Neither sweetener improved glucose intolerance, while solely OFS improved the disturbed colonic permeability. OFS decreased (-65±8%, P<0.001) plasma GLP-1 but not ghrelin and PYY levels in WT mice. Caecal acetate and butyrate levels were reduced by OFS in both genotypes suggesting enhanced uptake of short-chain fatty acids which may target FFAR2 (upregulated expression) in adipose tissue. Conclusion OFS, but not sucralose, reduced body weight gain and decreased intestinal permeability, but not glucose intolerance. Effects were not mediated by altered gut hormone levels or gustducin-mediated signaling. Artificial sweeteners do not affect gut hormone levels and are metabolically inert in mice on a high fat diet. In contrast, prebiotic oligosaccharides (OFS) prevent body weight gain but not glucose intolerance. Alterations in sweet and short-chain fatty acid receptors (FFAR) (studied in WT and α-gust−/− mice) which regulate gut hormone levels are not mandatory for the positive effects of OFS. Enhanced uptake of SCFAs may favor interaction with FFAR2/3 on adipose tissue to induce weight loss. This article is protected by copyright. All rights reserved