Fatty acid regulation of hepatic lipid metabolism.
Fatty acid regulation of hepatic lipid metabolism.
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DOI：
10.1097/mco.0b013e328342991c
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发表时间：
2011-03
影响因子：
3.1
通讯作者：
Jump DB
中科院分区：
文献类型：
--
作者：
Jump DB
探讨调节肝脏脂质代谢的转录机制。肥胖或患有糖尿病 (NIDDM) 或代谢综合征 (MetS) 的人血液和组织中 C20-22 多不饱和脂肪酸 (PUFA) 水平较低。尽管低 C20-22 PUFA 对人类疾病进展的影响尚不完全清楚，但对小鼠的研究提供了线索，表明 PUFA 代谢受损可能会导致与 NIDDM 和 MetS 相关的危险因素的严重程度。高脂肪饮食会促进 C57BL/6J 小鼠出现高血糖、胰岛素抵抗和脂肪肝，这种效应与 PUFA 合成相关酶的表达受到抑制以及肝脏 C20-22 PUFA 含量降低相关。相比之下，A/J 小鼠对饮食引起的肥胖和糖尿病具有抵抗力。这些小鼠参与 PUFA 合成的肝酶表达升高，并且 C20-22 PUFA 含量升高。此外，功能丧失和功能获得研究已确定脂肪酸延长酶 (Elovl5)（一种参与 PUFA 合成的关键酶）作为肝脏脂质和碳水化合物代谢的调节剂。 Elovl5 活性调节肝脏 C20-22 PUFA 含量、信号通路（Akt 和 PP2A）以及控制脂肪酸合成和糖异生的转录因子（SREBP-1、PPARα、FoxO1 和 PGC1α）。这些研究可能有助于确定控制与 NIDDM 和 MetS 相关的脂肪肝和高血糖的新策略。
To discuss transcriptional mechanisms regulating hepatic lipid metabolism. Humans who are obese or have diabetes (NIDDM) or metabolic syndrome (MetS) have low blood and tissue levels of C20–22 polyunsaturated fatty acids (PUFAs). Although the impact of low C20–22 PUFAs on disease progression in humans is not fully understood, studies with mice have provided clues suggesting that impaired PUFA metabolism may contribute to the severity of risk factors associated with NIDDM and MetS. High fat diets promote hyperglycemia, insulin resistance and fatty liver in C57BL/6J mice, an effect that correlates with suppressed expression of enzymes involved in PUFA synthesis and decreased hepatic C20–22 PUFA content. A/J mice, in contrast, are resistant to diet-induced obesity and diabetes; these mice have elevated expression of hepatic enzymes involved in PUFA synthesis and C20–22 PUFA content. Moreover, loss-of-function and gain-of-function studies have identified fatty acid elongase (Elovl5), a key enzyme involved in PUFA synthesis, as a regulator of hepatic lipid and carbohydrate metabolism. Elovl5 activity regulates hepatic C20–22 PUFA content, signaling pathways (Akt and PP2A) and transcription factors (SREBP-1, PPARα, FoxO1 and PGC1α) that control fatty acid synthesis and gluconeogenesis. These studies may help define novel strategies to control fatty liver and hyperglycemia associated with NIDDM and MetS.