2.3. Acute Exposure to Fish Oil Supplements Protect High Fat Diet Impaired Pancreatic Beta Cell Function

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Oral 2 - 2.3

1Dana Al Rijjal, 1Ying Liu, 1Michael Wheeler

1, Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada

Introduction: Omega-3 Fatty Acid (ω-3 FA) supplements derived from Fish Oil (FO) contain approximately 85% eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the two major components to which the health benefits of FO are generally attributed. The effect of fish intake in increasing the risk of Type 2 Diabetes (T2D) in humans is still controversial. We previously showed that EPA and DHA were both elevated in the serum of Gestational Diabetes Mellitus (GDM) patients. Therefore, whether FO components have a causative or preventive effect in prediabetes and T2D is still not known.

Methods and Result: To define the long-term effects of FO supplements in vivo, we deliver two omega-3 fatty acid supplements, Lovaza (containing 84% EPA and DHA) and Vascepa (containing 97% EPA), through oral gavage for one week prior to 6 weeks of High Fat Diet (HFD) feeding. Glucose tolerance test and insulin tolerance test were used to look at the effects on glucose homeostasis/ insulin sensitivity. The islets were isolated and glucose stimulated insulin secretion (GSIS) was done to look at the direct effects on pancreatic beta cell function. Remarkably, mice treated with Vascepa had reduced weight gain, improved glucose tolerance and insulin secretion in comparison to the HFD control group. Vascepa administration also protected mice from insulin resistance and impaired glucose stimulated insulin secretion (GSIS) at basal glucose 6 weeks after cessation of Vascepa treatment. This indicates that acute exposure of Vascepa has prolonged effects that could protect from the effects of a diet induced obesity on pancreatic beta cell function. In comparison, Lovaza, containing both EPA and DHA, had no effect on glucose tolerance, insulin secretion nor on insulin resistance indicating a possible specific effect of DHA or other FO components. Interestingly, Lovaza did protect islets from impaired GSIS suggesting a possible indirect effect of Lovaza on pancreatic beta cell function. To understand the acute effects of bioactive components of fish oil on pancreatic beta cell function in vitro, primary islets isolated from mice were treated with Lovaza, Vascepa, EPA and DHA and GSIS was performed. Islets treated acutely with Lovaza, Vascepa, EPA and DHA showed no difference in GSIS. Further experiments are required to understand the mechanism through which FO supplements affect pancreatic beta cell function and the component to which the effect can be attributed.

Conclusion: We demonstrate an effect of acute exposure of FO supplements on glucose tolerance and pancreatic beta cell function following a HFD induced mouse model. These results highlight the importance of characterizing the effect of individual FO components on beta cell function and understanding the mechanism through which FO supplements can prevent diet-induced diabetes.