Docosapentaenoic acid and docosahexaenoic acid are positively associated with insulin sensitivity in rats fed high‐fat and high‐fructose diets

Background We compared the insulin resistance and metabolic alterations by using a global lipidomic approach. Methods Rats were fed with high-fat-diet (HFD) and high-fructose-diet (HFr) for 12 weeks to induced insulin resistance syndrome. Results Rats on both diets developed of insulin resistance syndrome, characterized by hypertension, hyperlipidemia, hyperinsulinemia, impaired fasting glucose, and insulin resistance. Compared with HFr rats, nonesterified-fatty-acid was lower, and body weight and plasma insulin level were markedly higher in the HFD animals. Adiposity and plasma leptin levels were increased in both groups. However, the size of adipocytes in the HFD-fed rats was greater than that in the HFr-fed rats. Notably, the lipidomic heat map revealed metabolites exhibiting greater differences in the HFD and HFr-fed rats, compared with the controls. Plasma adrenic acid levels were higher in the HFD-fed rats than in the HFr-fed rats. Nevertheless, linoleic and arachidonic acid levels decreased in the HFr-fed rats. Plasma docosapentaenoic acid and docosahexaenoic acid were greatly reduced after feeding with both diets, particularly the HFr diet. Analyzing the correlation between these two fatty acids and metabolic parameters revealed a strong positive correlation between the acids and the insulin sensitivity index. Conclusions The systemic lipidomic analysis indicated that a reduction in these two long-chain fatty acids strongly correlated with insulin resistance in rats under long-term overnutrition. These results provide a potential therapeutic target of insulin resistance and metabolic syndrome.