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首页> 外文期刊>Current opinion in lipidology >Hepatic triglyceride synthesis and nonalcoholic fatty liver disease.
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Hepatic triglyceride synthesis and nonalcoholic fatty liver disease.

机译：肝甘油三酸酯合成和非酒精性脂肪肝疾病。

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PURPOSE OF REVIEW: Nonalcoholic fatty liver disease is a spectrum of diseases ranging from simple steatosis to cirrhosis. The hallmark of nonalcoholic fatty liver disease is hepatocyte accumulation of triglycerides. We will review the role of triglyceride synthesis in nonalcoholic fatty liver disease progression and summarize recent findings about triglyceride synthesis inhibition and prevention of progressive disease. RECENT FINDINGS: Attempts to inhibit triglyceride synthesis in animal models have resulted in improvement in hepatic steatosis. Studies in animal models of nonalcoholic fatty liver disease demonstrate that inhibition of acyl-coenzyme A:diacylglycerol acyltransferase, the enzyme that catalyzes the final step in triglyceride synthesis, results in improvement in hepatic steatosis and insulin sensitivity. We recently confirmed that hepatic specific inhibition of acyl-coenzyme A:diacylglycerol acyltransferase with antisense oligonucleotides improves hepatic steatosis in obese, diabetic mice but, unexpectedly, exacerbated injury and fibrosis in that model of progressive nonalcoholic fatty liver disease. When hepatocyte triglyceride synthesis was inhibited, free fatty acids accumulated in the liver, leading to induction of fatty acid oxidizing systems that increased hepatic oxidative stress and liver damage. These findings suggest that the ability to synthesize triglycerides may, in fact, be protective in obesity. SUMMARY: Nonalcoholic fatty liver disease is strongly associated with obesity and peripheral insulin resistance. Peripheral insulin resistance increases lipolysis in adipose depots, promoting increased free fatty acid delivery to the liver. In states of energy excess, such as obesity, the latter normally triggers hepatic triglyceride synthesis. When hepatic triglyceride synthesis is unable to accommodate increased hepatocyte free fatty acid accumulation, however, lipotoxicity results. Thus, rather than being hepatotoxic, liver triglyceride accumulation is actually hepato-protective in obese, insulin-resistant individuals.
机译：审查目的：非酒精性脂肪肝是一系列疾病，从单纯性脂肪变性到肝硬化。非酒精性脂肪肝的标志是甘油三酯的肝细胞积聚。我们将回顾甘油三酸酯合成在非酒精性脂肪肝疾病进展中的作用，并概述有关甘油三酸酯合成抑制和预防进行性疾病的最新发现。最近的发现：在动物模型中抑制甘油三酸酯合成的尝试已导致肝脂肪变性的改善。在非酒精性脂肪肝疾病动物模型中的研究表明，抑制酰基辅酶A：二酰基甘油酰基转移酶（一种催化甘油三酸酯合成最后一步的酶）可改善肝脂肪变性和胰岛素敏感性。我们最近证实，用反义寡核苷酸对酰基辅酶A：二酰基甘油酰基转移酶的肝特异性抑制作用可改善肥胖，糖尿病小鼠的肝脂肪变性，但出乎意料的是，在这种进行性非酒精性脂肪肝疾病模型中，肝损伤和纤维化加剧。当肝细胞甘油三酸酯的合成受到抑制时，游离脂肪酸在肝脏中积累，从而导致诱导脂肪酸氧化系统，从而增加了肝脏的氧化应激和肝脏损害。这些发现表明，合成甘油三酸酯的能力实际上可能对肥胖具有保护作用。摘要：非酒精性脂肪肝疾病与肥胖和外周胰岛素抵抗密切相关。周围胰岛素抵抗增加了脂肪库中的脂解作用，促进了游离脂肪酸向肝脏的递送增加。在能量过剩的状态下，例如肥胖，后者通常会触发肝甘油三酸酯的合成。但是，当肝甘油三酸酯的合成不能适应增加的肝细胞游离脂肪酸积累时，会产生脂毒性。因此，甘油三酸酯的积累而不是具有肝毒性，实际上在肥胖，胰岛素抵抗的个体中具有肝保护作用。

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