Purified diets are obesigenic, promote insulin resistance and confer sensitivity to chemical colitogens

The paradigm that an obesigenic metabolic profile results from excess caloric intake has come under question as a growing number of caveats, especially that predisposition to insulin resistance and obesity is heritable, through epigenetic and microbiotal mechanisms, and self‐perpetuating, as adipose tissue is both a source and sink for inflammatory actors, emerge. As obesity penetrance increases in developing countries on adoption of Western diet and food processing regimes, it seems logical to investigate the obesigenic potential of highly processed, although nominally chow‐equivalent, diets in mice. Naturally sourced chow and purified 10% saturated fat diets were given to 4 week old mice whose weights were followed for 12 weeks at which time metabolic and inflammatory parameters were assessed. Further, chow‐ and purified diet‐fed mice were subjected to chronic and acute models of DSS colitis. We report that purified diets induce weight gain and insulin resistance relative to isocaloric naturally‐sourced chow. Purified diet also induced mild splenomegaly and wasting of intestinal tissues accompanied by increases in neutrophil infiltration, proinflammatory cytokines and acute phase proteins, perhaps reflecting diet‐mediated degradation of barrier function. Purified diet‐fed mice were sensitive to DSS‐induced mortality and weight loss immediately following co‐administration of purified diets. Grant Funding Source : NIH