Effect of omega-3 fatty acids on glucose homeostasis: role of free fatty acid receptor 1.

Abstract

Insulin resistance is a worldwide health problem. This study investigated the acute effects of eicosapentanoic acid (EPA) on glucose homeostasis focusing on the role of free fatty acid receptor 1 (FFAR1) and the chronic effects of fish oil omega-3 fatty acids on insulin resistance. Insulin resistance was induced by feeding mice high-fructose, high-fat diet (HFrHFD) for 16weeks. In the first part, the acute effects of EPA alone and in combination with GW1100 and DC260126 (FFAR1 blockers) on glucose homeostasis and hepatic phosphatidyl-inositol 4,5-bisphosphate (PIP2) and diacylglycerol (DAG) were investigated in standard chow diet (SCD)- and HFrHFD-fed mice. In the second part, mice were treated with fish oil omega-3 fatty acids for 4weeks starting at the week 13 of feeding HFrHFD. Changes in the blood- and liver tissue-insulin resistance markers and FFAR1 downstream signals were recorded at the end of experiment. Results showed that EPA increased 0 and 30min blood glucose levels after glucose load in SCD-fed mice but improved glucose tolerance in HFrHFD-fed mice. Moreover, FFAR1 blockers reduced EPA effects on glucose tolerance and hepatic PIP2 and DAG levels. On the other hand, chronic use of fish oil omega-3 fatty acids increased FBG levels and decreased serum insulin and triglycerides levels without improving the index of insulin resistance. Also, they increased hepatic β-arrestin-2, PIP2, and pS473 Akt levels but decreased DAG levels. In conclusion, EPA acutely improved glucose homeostasis in HFrHFD-fed mice by modulating the activity of FFAR1. However, the chronic use of fish oil omega-3 fatty acids did not improve the insulin resistance.