Corporeau Charlotte, Le Foll Christelle, Cruciani-Guglielmacci Céline, Le Stunff Hervé, Mithieux Gilles, Magnan Christophe, Delarue Jacques
Department of Nutritional Sciences, Hospital University, Faculty of Medicine, University of Brest, Plouzané, France.
Present address: Ifremer, University of Brest, CNRS, IRD, LEMAR, F-29280 Plouzané, France.
Br J Nutr. 2024 Mar 14;131(5):749-761. doi: 10.1017/S0007114523002404. Epub 2023 Oct 25.
Long-chain -3 PUFA (LC -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), while the control group was fed a diet containing 8 % fat from CO (wt/wt) (ZO). Male lean Zucker (ZL) rats fed either FO (ZL) or CO (ZL) 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 only. Liver insulin sensitivity (euglycaemic-hyperinsulinaemic clamp + 2 deoxyglucose) was improved in ZO 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 and ZO. Hypothalamic ceramides levels were lower in ZO than in ZO. Our study demonstrates that LC -3 PUFA can minimise weight gain, possibly by alleviating hypothalamic lipotoxicity, and liver IR in genetically obese Zucker rats.
长链-3多不饱和脂肪酸（LC-3 PUFA）在啮齿动物中可预防由高脂和/或果糖饮食诱导的胰岛素抵抗（IR），但不能预防由糖皮质激素诱导的IR。在人类中，也有相互矛盾的报道。我们研究了它们在遗传性胰岛素抵抗的雄性肥胖（fa/fa） Zucker（ZO）大鼠肥胖发展过程中对胰岛素敏感性、采食量（FI）和体重增加的影响。给ZO大鼠喂食补充了7%鱼油（FO）+1%玉米油（CO）（重量/重量）的饮食（ZO组），而对照组喂食含有8%来自CO的脂肪（重量/重量）的饮食（ZO组）。喂食FO（ZL组）或CO（ZL组）饮食的雄性瘦Zucker（ZL）大鼠用作对照。FO是一种海洋来源的甘油三酯油，含有90毫克/克的二十碳五烯酸（EPA）+430毫克/克的二十二碳六烯酸（DHA）。在口服葡萄糖耐量试验期间，FO对葡萄糖耐量没有影响，而仅在ZO大鼠中胰岛素反应降低。ZO大鼠的肝脏胰岛素敏感性（正常血糖-高胰岛素钳夹+2-脱氧葡萄糖）得到改善，这与磷酸烯醇式丙酮酸羧激酶的表达、活性以及葡萄糖-6-磷酸酶活性的变化有关。在ZO和ZO大鼠中，对颈动脉内胰岛素/葡萄糖输注的反应，采食量同样降低。ZO大鼠下丘脑神经酰胺水平低于ZO大鼠。我们的研究表明，LC-3 PUFA可能通过减轻下丘脑脂毒性，使遗传性肥胖的Zucker大鼠体重增加最小化，并改善肝脏IR。
