Liver triglyceride secretion and lipid oxidative metabolism are rapidly altered by leptin in vivo
Liver triglyceride secretion and lipid oxidative metabolism are rapidly altered by leptin in vivo
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DOI：
10.1210/en.2005-0731
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发表时间：
2006-03-01
期刊：
影响因子：
4.8
通讯作者：
O'Doherty, RM
中科院分区：
文献类型：
--
作者：
Huang, W;Dedousis, N;O'Doherty, RM
瘦素在外周组织和血浆中具有强大的降脂作用，这被认为是预防细胞脂毒性和胰岛素抵抗的重要因素。本文综述了急性瘦素给药对肝脏甘油三酯(TG)代谢的影响，肝脏瘦素作用对全身TG稳态的影响，以及瘦素作用的机制。瘦大鼠静脉注射瘦素120min后，肝脏甘油三酯水平下降(53+/-3%，P=0.001)，而骨骼肌甘油三酯水平无明显变化，肝脏磷脂酰肌醇3-激酶活性升高(341+/-95%，P=0.01)。瘦素对饮食诱导肥胖大鼠肝脏甘油三酯水平和磷脂酰肌醇3-激酶活性无影响。瘦素可降低瘦肉动物血浆甘油三酯浓度(20+/-7%；P=0.017)、泰洛沙普治疗后血浆甘油三酯蓄积率(26+/-6%；P=0.003)和肝脏甘油三酯分泌量(51+/-8%；P=0.004)。为了确定耗竭的肝脏甘油三酯可能的代谢命运，我们评估了瘦素对肝脏氧化代谢的影响。瘦素使肝乙酰辅酶A羧化酶磷酸化(85+/-13%；P=0.006)、脂肪酸氧化(49+/-7%；P=0.001)和酮体生成(69+/-15%；P=0.004)增加。侧脑室注射瘦素120min对肝脏甘油三酯水平无影响，但使信号转导和转录激活子3磷酸化水平增加(162+/-40%；P=0.02)。这些数据提供了体内证据，证明瘦素在肝脏甘油三酯代谢和全身甘油三酯动态平衡的急性调节中发挥作用。这些效应的一个可能的作用机制是瘦素诱导的甘油三酯进入氧化途径。
Leptin has potent lipid-lowering effects in peripheral tissues and plasma that are proposed to be important for the prevention of cellular lipotoxicity and insulin resistance. The current study addressed in vivo the effects of acute leptin delivery on liver triglyceride (TG) metabolism, the consequence of hepatic leptin action on whole-body TG homeostasis, and the mechanisms of leptin action. A 120-min iv leptin infusion (plasma leptin, similar to 14 ng/ml) decreased liver TG levels (53 +/- 3%; P = 0.001), but not skeletal muscle TG levels, and increased liver phosphatidylinositol 3-kinase activity (341 +/- 95%; P = 0.01) in lean rats. Leptin had no effect on liver TG levels or phosphatidylinositol 3-kinase activity in diet-induced obese rats. In lean animals, leptin decreased the plasma TG concentration (20 +/- 7%; P = 0.017), the rate of TG accumulation in plasma after tyloxapol administration (26 +/- 6%; P = 0.003), and TG secretion from isolated liver (51 +/- 8%; P = 0.004). To determine possible metabolic fates of depleted hepatic TG, we assessed leptin effects on liver oxidative metabolism. Leptin increased hepatic acetyl-coenzyme A carboxylase phosphorylation (85 +/- 13%; P = 0.006), fatty acid oxidation (49 +/- 7%; P = 0.001) and ketogenesis (69 +/- 15%; P = 0.004). Finally, intrace-rebroventricular delivery of leptin for 120 min had no effect on liver TG levels, but did increase signal transducer and activator of transcription 3 phosphorylation (162 +/- 40%; P = 0.02). These data present in vivo evidence for a role for leptin in the acute regulation of hepatic TG metabolism, and whole body TG homeostasis. A likely contributing mechanism for these effects is leptin-induced partitioning of TG into oxidative pathways.