Functional Effects of the Buckwheat Iminosugar D-Fagomine on Rats with Diet-Induced Prediabetes

Scope: The goals of this work are 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 D-fagomine (or not, for comparison) or a standard diet (controls) for 24weeks. The variables measured were fasting blood glucose and insulin levels; glucose tolerance; diacylglycerols as intracellular mediators of insulin resistance in adipose tissue (AT), liver, and muscle; inflammation markers (plasma IL-6 and leptin, and liver and AT histology markers); eicosanoids from arachidonic acid as lipid mediators of inflammation; and the populations of Bacteroidetes, Firmicutes, Enterobacteriales, and Bifidobacteriales in feces. It was found that D-fagomine reduces fat-induced impaired glucose tolerance, inflammation markers, and mediators (hepatic microgranulomas and lobular inflammation, plasma IL-6, prostaglandin E-2, and leukotriene B-4) 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.