The Mechanisms of Neochlorogenic Acid (3-Caffeoylquinic Acid) in Improving glucose and Lipid Metabolism in Rats with Insulin Resistance Induced by A High Fat-High Fructose Diet

Abstract

This study investigated the effects and the mechanism of actions of neochlorogenic acid (3-caffeoylquinic acid; 3-CQA) on glucose and lipid metabolism in rats fed a high fat-high fructose diet (HFFD). Male rats were fed HFFD (40 % lard and 20 % fructose) for 16 weeks. At the 10th week, the HFFD rats were split into 3 groups: HFFD receiving distilled water (HFFD control group), HFFD receiving 3-CQA 50 mg/kg and HFFD receiving metformin 200 mg/kg once daily for a further 6 weeks. At the end of treatment, fasting blood glucose (FBG), oral glucose-tolerance test (OGTT), lipid profile, insulin, leptin, adiponectin, markers of oxidative stress, and hepatic triglyceride content were measured. Liver, adipose tissue, and skeletal muscle were collected for histological, gene and protein examinations. Compared to the HFFD control group, the 3-CQA group exhibited significantly reduced FBG, insulin and leptin levels, and improved OGTT. Serum adiponectin increased and lipid profiles were normalized. Hepatic triglyceride was reduced with a decrease in lipid droplets in liver histological sections. Levels of serum SOD and CAT activity, and MDA were reversed by 3-CQA treatment. Moreover, 3-CQA significantly reduced the expression of adipocyte pro-inflammatory cytokine genes (MCP-1, TNF-α, and IL-6), hepatic lipogenic genes (SREBP1c, FAS, and GPAT), and hepatic gluconeogenic genes (PEPCK and G6Pase). Additionally, 3-CQA increased expression of muscle GLUT4 gene, and of GLUT4 protein with increased p-AKT and p-AMPK in skeletal muscle. In conclusion, 3-CQA improves glucose and lipid metabolism plausibly by decreasing oxidative stress and inflammation-induced insulin resistance, downregulating the expression of lipogenic and gluconeogenic genes, and enhancing insulin signaling in HFFD-induced insulin-resistant rats. HIGHLIGHTS Neochlorogenic acid (3-CQA) improves glucose and lipid metabolism by decreasing insulin resistance Neochlorogenic acid (3-CQA) deceases insulin resistance due to its activities in ameliorating obesity, oxidative stress, and adipose tissue inflammation The beneficial effects of Neochlorogenic acid (3-CQA) to improve glucose and lipid homeostasis may be mediated via suppression of hepatic glucose production and lipogenesis, and activation of muscle glucose uptake and AKT and AMPK pathways GRAPHICAL ABSTRACT