Resistant starch intake partly restores metabolic and inflammatory alterations in the liver of high-fat-diet-fed rats.

Insulin resistance (IR) constitutes the most important feature of the metabolic syndrome, whose prevalence is highly associated to the consumption of Western diets. Resistant starch (RS) consumption has been shown to have beneficial metabolic effects, including improved insulin sensitivity, and glucose and lipid homeostasis. However, the mechanisms (especially at the molecular level) by which this takes place are still not completely known. In the present study, we aimed to evaluate the role of the liver in the ameliorated high-fat (HF)-induced IR status by RS. Thus, three groups of rats were fed either a control diet, or an HF diet containing or not RS. After 9 weeks of feeding, we evaluated the whole-body insulin sensitivity, and the hepatic glucose and lipid metabolism at the biochemical and molecular levels and the metabolome of the cecum content. We demonstrated for the first time that at least part of the beneficial effects of RS consumption in the context of an HF feeding can be driven by changes elicited at the hepatic level. The ability of the RS to correct the HF-induced dyslipidemia and the associated IR resulted from the return to the basal expression levels of transcription factors involved in lipogenesis (SREBP-1c), cholesterol metabolism (SREBP-2, LXRs) and fatty acid oxidation (PPARα). Moreover, the RS feeding was able to correct the HF-induced reduction in hepatic glucose phosphorylation and muscle glucose transport, improving glucose tolerance. Finally, as a whole, the improved hepatic metabolism seemed to be the result of an ameliorated inflammatory status.