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 24 weeks. 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 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.