Lack of soluble fiber drives diet-induced adiposity in mice

Abstract

Diet-induced obesity is often modeled by comparing mice fed high-fat diet (HFD), which is made from purified ingredients, vs. normal chow diet (NCD), which is a low-fat assemblage of relatively unrefined plant and animal products. The mechanism by which HFD promotes adiposity is complex but thought to involve low-grade inflammation and altered gut microbiota. The goal of this study was to investigate the extent to which HFD-induced adiposity is driven by fat content vs. other factors that differentiate HFD vs. NCD. Mice were fed NCD, HFD, or other compositionally defined diets (CDD), designed to mimic NCD and/or explore the role of HFD components. A range of metabolic parameters reflecting low-grade inflammation and adiposity were assayed. Relative to NCD, HFD, and to a lesser, but, nonetheless, significant extent, CDD induced increased adiposity, indicating both lipid content and other aspects of HFD are obesogenic. Moreover, HFD and CDD induced a rapid and marked loss of cecal and colonic mass. Such CDD-induced effects were not affected by adjusting dietary protein levels/types but could be largely eliminated by exchanging insoluble fiber (cellulose) for soluble fiber (inulin). Replacing cellulose with inulin in HFD also protected mice against decreased intestinal mass, hyperphagia, and increased adiposity. Such beneficial effects of inulin were microbiota dependent, correlated with elevated fecal short-chain fatty acid levels analyzed via 1H-NMR-based metabolomics and were partially recapitulated by administration of short-chain fatty acid. HFD-induced obesity is strongly promoted by its lack of soluble fiber, which supports microbiota-mediated intestinal tissue homeostasis that prevents inflammation driving obesity and metabolic syndrome.

How diet can impact gut microbiota to promote or endanger health

“…For example, Martens and colleagues observed that lack of fiber resulted in microbiota consuming the mucus layer, which made the intestine more prone to attack by invasive pathogens [21]. We observed that lack of fermentable fibers results in greatly reduced epithelial cell proliferation that leads to a thin mucosa in which but bacteria readily encroach [22,23]. Such effects on host-microbiota interaction promoted low-grade inflammation that underlined a significant portion of metabolic syndrome induced by HFD, which is generally devoid of fermentable fiber, and were sufficient to promote a significant degree of adiposity even in the context of a low-fat diet [22,23].…”

“…We observed that lack of fermentable fibers results in greatly reduced epithelial cell proliferation that leads to a thin mucosa in which but bacteria readily encroach [22,23]. Such effects on host-microbiota interaction promoted low-grade inflammation that underlined a significant portion of metabolic syndrome induced by HFD, which is generally devoid of fermentable fiber, and were sufficient to promote a significant degree of adiposity even in the context of a low-fat diet [22,23]. Conversely, supplementing HFD with the fermentable fiber inulin but not the insoluble fiber cellulose resulted in a microbiota-dependent fortification of the mucosa that prevented microbiota encroachment and protected against HFD-induced metabolic syndrome [22,23].…”

“…Such effects on host-microbiota interaction promoted low-grade inflammation that underlined a significant portion of metabolic syndrome induced by HFD, which is generally devoid of fermentable fiber, and were sufficient to promote a significant degree of adiposity even in the context of a low-fat diet [22,23]. Conversely, supplementing HFD with the fermentable fiber inulin but not the insoluble fiber cellulose resulted in a microbiota-dependent fortification of the mucosa that prevented microbiota encroachment and protected against HFD-induced metabolic syndrome [22,23]. Interestingly, such protective effects of fermentable fiber were not largely mediated by SCFA generation but rather were mediated by induction of IL-22, whose levels were depleted by lack of fiber and restored by inulin in a microbiota-dependent manner.…”

“…Moreover, our observations in mouse studies suggest that great caution is needed in considering approaches to supplement diets with purified fibers. Specifically, while enriching HFD with inulin prevented HDD-induced gut atrophy and greatly reduced metabolic syndrome [22,23], it did not restore gut microbiota composition per se but rather resulted in a new community structure altogether. Moreover, mice consuming inulin-enriched purified diets, of low or high fat content, developed extremely severe colitis upon exposure to the chemical DSS [23].…”

The Western Diet–Microbiome-Host Interaction and Its Role in Metabolic Disease

“…However, several other dietary factors could be contributing. An animal study demonstrated that changes in microbiota leading to intestinal inflammation were caused by the lack of fermentable fiber, and not by the content of fat in the diet [68]. When mice were fed a diet that induced metabolic endotoxemia, adding a prebiotic improved metabolic markers [69].…”