Although most of the proposed beneficial effects of fiber consumption have been attributed to viscous and gel-forming properties of soluble fiber, it is mainly insoluble cereal fiber and whole grains that are strongly associated with reduced diabetes risk in prospective cohort studies, indicating that other unknown mechanisms are likely to be involved.\ud \ud We performed a long-term study investigating potential protective effects of adding soluble guar fiber (10% w/w) vs. insoluble cereal fiber (10% w/w) to an isoenergetic and macronutrient matched high-fat diet in obesity-prone C57BL/6J mice. After 45 weeks, mice fed soluble vs. insoluble fiber showed both significantly increased body weight (41.8±3.0 vs. 33.6±1.5 g, P=.03) and elevated markers of insulin resistance. In mice fed soluble fiber, energy loss via the feces was significantly lower and colonic fermentation with production of short chain fatty acids (SCFA) was markedly increased. Gene expression analysis in white adipose tissue showed significantly increased levels of the fatty acid target G-protein coupled receptor-40 in soluble fiber-fed mice. Liver gene expression in the insoluble fiber group showed a pattern consistent with increased fatty acid oxidation. The present results show that soluble vs insoluble dietary fiber added to a high-fat, Western-style diet differently affected body weight and estimates of insulin sensitivity in obesity-prone mice. Soluble fiber intake with increased SCFA production significantly contributed to digested energy, thereby potentially outweighing the well known short-term beneficial effects of soluble fiber consumption.\ud \u
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