Effect of omega-3 fatty acids on glucose homeostasis: role of free fatty acid receptor 1
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ORIGINAL ARTICLE
Effect of omega-3 fatty acids on glucose homeostasis: role of free fatty acid receptor 1 Shaimaa H. El-Fayoumi 1 & Amr A. A. Mahmoud 1,2 & Ahmed Fahmy 1 & Islam A. A. E.-H. Ibrahim 1 Received: 31 January 2020 / Accepted: 22 April 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
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 16 weeks. 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 4 weeks 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 30 min 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. Keywords Omega-3 fatty acids . β-Arrestin-2 . Free fatty acid receptor 1 . Insulin resistance . High-fructose, high-fat diet
Introduction Insulin resistance is a condition in which the response of peripheral tissues to insulin is attenuated. Sedentary lifestyle, excessive consumption of fast-food rich in saturated fats, and high-fructose drinks are the main causes of this disorder (Basciano et al. 2005). This metabolic disorder is associated with increased gluconeogenesis, glycogenolysis, hepatic glucose output, lipolysis, and hyperlipidemia (Home and Pacini Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00210-020-01883-5) contains supplementary material, which is available to authorized users. * Islam A. A. E.-H. Ibrahim [email protected] 1
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt
2
Present address: Department of Pharmacology, Pharmacy Program, Oman College of Health Sciences, 114 Muscat, Oman
2008; Boden 2011). Moreover, ectop
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