Fish oil minimises feed intake and improves insulin sensitivity in Zucker fa/fa rats

Abstract

Long chain n-3 fatty acids (LC n-3 PUFA) prevent, in rodents, insulin-resistance (IR) induced by a high fat and/or fructose diet, but not IR induced by glucocorticoids. In humans, contrasting effects have also been reported. We investigated their effects on insulin sensitivity, feed intake, and body weight gain in genetically insulin resistant male obese (fa/fa) Zucker rats (ZO) during the development of obesity. ZO rats were fed a diet supplemented with 7% fish oil + 1% corn oil (wt/wt) (ZOFO), while the control group was fed a diet containing 8% fat from corn oil (wt/wt) (ZOCO). Male lean Zucker (ZL) rats fed either FO (ZLFO) or CO (ZLCO) diet were used as controls. FO was a marine-derived triglyceride oil containing EPA 90 mg/g + DHA 430 mg/g. During an oral glucose tolerance test, glucose tolerance remained unaltered by FO while insulin response was reduced in ZOFO only. Liver insulin sensitivity (euglycemic hyperinsulinemic clamp + 2 deoxy-glucose) was improved in ZOFO rats, linked to changes in PEPCK expression, activity and G6Pase activity. Feed intake in response to intra-carotid insulin/glucose infusion was decreased similarly in ZOFO and ZOCO. Hypothalamic ceramides levels were lower in ZOFO than in ZOCO. Our study demonstrates that LC n-3 PUFA can minimize weight gain, possibly by alleviating hypothalamic lipotoxicity, and liver insulin-resistance in genetically obese Zucker rats.