Functional effects of the buckwheat iminosugar D-fagomine on rats with diet-induced prediabetes

Abstract

Scope: The goals of this work were to test if D-fagomine, an iminosugar that reduces body weight gain, can delay the appearance of a fat-induced prediabetic state in a rat model and to explore possible mechanisms behind its functional action. Methods and results: Wistar Kyoto rats were fed a high-fat diet supplemented with D7 fagomine (or not; for comparison) or a standard diet (controls) for 24 weeks. The variables measured were: fasting blood glucose and insulin levels; glucose tolerance; diacylglycerols as intracellular mediators of insulin resistance in adipose tissue, liver and muscle; inflammation markers (plasma IL-6 and leptin, and liver and adipose tissue histology markers); eicosanoids from arachidonic acid as lipid mediators of inflammation; and the populations of Bacteroidetes, Firmicutes, Enterobacteriales and Bifidobacteriales in feces. We found that D-fagomine reduces fat-induced impaired glucose tolerance, inflammation markers and mediators (hepatic microgranulomas and lobular inflammation, plasma IL-6, prostaglandin E2 and leukotriene B4) while attenuating the changes in the populations of Enterobacteriales and Bifidobacteriales. Conclusion: D-Fagomine delays the development of a fat-induced prediabetic state in rats by reducing low-grade inflammation. We suggest that the anti-inflammatory effect of D-fagomine may be linked to a reduction in fat-induced overpopulation of minor gut bacteria.