Naringin ameliorates metabolic syndrome by activating AMP-activated protein kinase in mice fed a high-fat diet

Metabolic syndrome is a low-grade inflammatory state in which oxidative stress is involved. Naringin, isolated from the Citrussinensis, is a phenolic compound with anti-oxidative and anti-inflammatory activities. The aim of this study was to explore the effects of naringin on metabolic syndrome in mice. The animal models, induced by high-fat diet in C57BL/6 mice, developed obesity, dyslipidemia, fatty liver, liver dysfunction and insulin resistance. These changes were attenuated by naringin. Further investigations revealed that the inhibitory effect on inflammation and insulin resistance was mediated by blocking activation of the MAPKs pathways and by activating IRS1; the lipid-lowering effect was attributed to inhibiting the synthesis way and increasing fatty acid oxidation; the hypoglycemic effect was due to the regulation of PEPCK and G6pase. The anti-oxidative stress of naringin also participated in the improvement of insulin resistance and lipogenesis. All of these depended on the AMPK activation. To confirm the results of the animal experiment, we tested primary hepatocytes exposed to high glucose system. Naringin was protective by phosphorylating AMPKα and IRS1. Taken together, these results suggested that naringin protected mice exposed to a high-fat diet from metabolic syndrome through an AMPK-dependent mechanism involving multiple types of intracellular signaling and reduction of oxidative damage.

Graphical abstractFigure optionsDownload full-size imageDownload high-quality image (214 K)Download as PowerPoint slideHighlights► Naringin leads to pleiotropic effects on metabolic syndrome. ► The mechanisms of naringin on metabolic syndrome are dependent on AMPK activation. ► Naringin has no liver toxicity.