INRA, UR1067 Nutrition Metabolism Aquaculture, F-64310 Saint-Pée-sur-Nivelle, France.
J Anim Sci. 2011 Oct;89(10):3079-88. doi: 10.2527/jas.2010-3733. Epub 2011 May 13.
Carbohydrate energy intake in excess of total energy expenditure is converted to fat. In fish, the liver is considered to be the main lipogenic tissue. Its regulation by insulin is not fully understood, and some of the available in vivo findings are contradictory. In this study, bovine insulin was infused for 5 d into rainbow trout fed a high-carbohydrate diet, and variables of de novo hepatic lipogenesis were measured. We found that hepatic lipogenesis in trout is stimulated by insulin, reflected in enhanced mRNA and protein abundance and enzyme activity of ATP-citrate lyase, acetyl-CoA carboxylase, and fatty acid synthase. These results were further supported by parallel changes in enzymes acting as NAD phosphate donors, especially those participating in the pentose phosphate pathway. This is the first time that the main enzymes involved in de novo hepatic lipogenesis have been studied at the molecular, protein, and activity levels in fish. We hypothesize that some of the delayed changes found in the different levels of regulation were probably related to the insulin resistance achieved by the trout liver after 5 d of insulin infusion. We assessed enzyme activity and mRNA abundance of lipid oxidation-related enzymes in the livers of insulin-infused fish in which paradoxically increased β-oxidation potential was found. The insulin-stimulated de novo hepatic lipogenesis in carbohydrate-fed trout reinforces the hypothesis that this pathway may act as an important sink for excess glucose, which could ultimately contribute to improved glucose homeostasis in this carnivorous and glucose-intolerant species when fed high-carbohydrate diets.
碳水化合物摄入超过总能量消耗会转化为脂肪。在鱼类中，肝脏被认为是主要的生脂组织。其受胰岛素的调节尚未完全了解，一些现有的体内发现结果是相互矛盾的。在这项研究中，牛胰岛素被输注到摄食高碳水化合物饮食的虹鳟鱼体内 5 天，并测量了从头合成肝脂肪生成的变量。我们发现胰岛素刺激了鱼类的肝脂肪生成，反映在 ATP-柠檬酸裂解酶、乙酰辅酶 A 羧化酶和脂肪酸合酶的 mRNA 和蛋白丰度以及酶活性增强。这些结果得到了作为 NAD 磷酸供体的酶平行变化的进一步支持，特别是那些参与戊糖磷酸途径的酶。这是首次在鱼类中从分子、蛋白和活性水平研究从头合成肝脂肪生成的主要酶。我们假设，在不同的调控水平上发现的一些延迟变化可能与胰岛素输注 5 天后鱼类肝脏的胰岛素抵抗有关。我们评估了胰岛素输注鱼类肝脏中与脂质氧化相关的酶的酶活性和 mRNA 丰度，尽管发现了矛盾的β-氧化潜力增加。碳水化合物喂养的虹鳟鱼中胰岛素刺激的从头合成肝脂肪生成加强了这样一种假设，即该途径可能作为多余葡萄糖的重要储存库发挥作用，当喂食高碳水化合物饮食时，这最终有助于提高这种肉食性和不耐糖的物种的葡萄糖稳态。
