Combination Of Fructose And Stress Induces Insulin Resistance And Disturbs Lipid Metabolism In Muscle And Adipose Tissue Of Rats

Abstract

Background: Increased consumption of caloric food rich in fructose and daily exposure to unpredictable stress became hallmarks of modern lifestyle and have been associated with the development of metabolic syndrome, type2 diabetes and cardiovascular diseases1,2. Visceral adipose tissue (VAT) and muscles are important centers of lipid and glucose metabolism and metabolic disturbances in these organs and their crosstalk could vastly contribute to the development of metabolic diseases3,4. The aim: To elucidate whether prolonged combination of fructose over consumption and chronic stress disturbs lipid metabolism and insulin signaling in rat VAT and muscle. Methods: We examined the effects of 9-week fructose-enriched diet with and without exposure to unpredictable stress on expression of genes and level of proteins involved in lipid uptake (lipoprotein lipase, fatty acid translocase and fatty acid transport protein), de novo lipogenesis (acetyl-CoA carboxylase and fatty acid synthase), lipolysis (hormone sensitive lipase and adipose triglyceride lipase) and fatty acids oxidation (carnitine palmitoyltransferase I) in VAT and muscle of male Wistar rats. Additionally, muscle insulin signaling was analyzed at the level of insulin receptor substrate-1 (IRS1) and Akt kinase, and their activating and inhibitory phosphorylations. Results: Combination of fructose overconsumption and stress increased plasma insulin and free fatty acids level, upregulated expression of both lipolytic and lipogenic genes in VAT and stimulated lipid uptake, lipolysis and β-oxidation in muscle. Furthermore, reduced protein content and stimulatory phosphorylation of IRS1 and Akt kinase, together with unchanged inhibitory phosphorylation of IRS1 was observed in muscle. Conclusions: The results show that the combination of fructose over consumption and chronic stress disturbs lipid metabolism in VAT and muscle. Importantly, upregulated VAT lipolysis elevates plasma free fatty acids, which intensify their influx to muscles possibly leading to muscle insulin resistance detected in fructose fed stressed rats.