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


Corporeau, Charlotte; Le Foll, Christelle; Cruciani-Guglielmacci, Céline; Le Stunff, Hervé; Mithieux, Gilles; Magnan, Christophe; Delarue, Jacques (2024). Fish oil minimises feed intake and improves insulin sensitivity in Zucker fa/fa rats. The British Journal of Nutrition, 131(5):749-761.

Abstract

Long-chain n-3 PUFA (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 (FI) and body weight gain in genetically insulin resistant male obese (fa/fa) Zucker (ZO) rats during the development of obesity. ZO rats were fed a diet supplemented with 7 % fish oil (FO) + 1 % corn oil (CO) (wt/wt) (ZO$_{FO}$), while the control group was fed a diet containing 8 % fat from CO (wt/wt) (ZO$_{CO}$). Male lean Zucker (ZL) rats fed either FO (ZL$_{FO}$) or CO (ZL$_{CO}$) diet were used as controls. FO was a marine-derived TAG 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 ZO$_{FO}$ only. Liver insulin sensitivity (euglycaemic–hyperinsulinaemic clamp + 2 deoxyglucose) was improved in ZO$_{FO}$ rats, linked to changes in phosphoenolpyruvate carboxykinase expression, activity and glucose-6-phosphatase activity. FI in response to intra-carotid insulin/glucose infusion was decreased similarly in ZO$_{FO}$ and ZO$_{CO}$. Hypothalamic ceramides levels were lower in ZO$_{FO}$ than in ZO$_{CO}$. Our study demonstrates that LC n-3 PUFA can minimise weight gain, possibly by alleviating hypothalamic lipotoxicity, and liver IR in genetically obese Zucker rats.

Abstract

Long-chain n-3 PUFA (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 (FI) and body weight gain in genetically insulin resistant male obese (fa/fa) Zucker (ZO) rats during the development of obesity. ZO rats were fed a diet supplemented with 7 % fish oil (FO) + 1 % corn oil (CO) (wt/wt) (ZO$_{FO}$), while the control group was fed a diet containing 8 % fat from CO (wt/wt) (ZO$_{CO}$). Male lean Zucker (ZL) rats fed either FO (ZL$_{FO}$) or CO (ZL$_{CO}$) diet were used as controls. FO was a marine-derived TAG 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 ZO$_{FO}$ only. Liver insulin sensitivity (euglycaemic–hyperinsulinaemic clamp + 2 deoxyglucose) was improved in ZO$_{FO}$ rats, linked to changes in phosphoenolpyruvate carboxykinase expression, activity and glucose-6-phosphatase activity. FI in response to intra-carotid insulin/glucose infusion was decreased similarly in ZO$_{FO}$ and ZO$_{CO}$. Hypothalamic ceramides levels were lower in ZO$_{FO}$ than in ZO$_{CO}$. Our study demonstrates that LC n-3 PUFA can minimise weight gain, possibly by alleviating hypothalamic lipotoxicity, and liver IR in genetically obese Zucker rats.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Veterinärwissenschaftliches Institut > Institute of Veterinary Physiology
Dewey Decimal Classification:570 Life sciences; biology
Scopus Subject Areas:Health Sciences > Medicine (miscellaneous)
Health Sciences > Nutrition and Dietetics
Uncontrolled Keywords:Nutrition and Dietetics, Medicine (miscellaneous)
Language:English
Date:14 March 2024
Deposited On:18 Dec 2023 13:28
Last Modified:11 Jul 2024 03:32
Publisher:Cambridge University Press
ISSN:0007-1145
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1017/s0007114523002404
PubMed ID:37877265