Hepatocyte-specific eNOS deletion impairs exercise-induced adaptations in hepatic mitochondrial function and autophagy.
Hepatocyte-specific eNOS deletion impairs exercise-induced adaptations in hepatic mitochondrial function and autophagy.
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DOI：
10.1002/oby.23414
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发表时间：
2022-05
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影响因子：
--
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内皮型一氧化氮合酶（eNOS）是运动诱导的肝线粒体适应的潜在介质。在这里，雄性和雌性肝细胞特异性eNOS敲除（eNOShep−/−）和完整的肝eNOS（eNOSfl/fl）小鼠进行自愿轮跑运动（EX）或保持在久坐的笼子条件下10周。EX解决了eNOShep−/−雄性小鼠的肝脂肪变性加重。用EX完全消融升高的H2 O2排放（eNOShep−/−比eNOSfl/fl小鼠高约50%）。有趣的是，EX增加了雄性eNOSfl/fl中的[1- 14 C]棕榈酸氧化，但这在eNOShep−/−雄性小鼠中是钝的。与eNOSfl/fl小鼠相比，eNOShep−/−小鼠具有较低的能量传感器pAMPK/AMPK和mTOR和p-mTOR标记，以及自噬引发剂ULK 1和pULK 1。雌性动物显示ETC蛋白含量和线粒体生物发生标志物（TFAM，pgc 1 α）升高。总的来说，我们首次证明了在雄性小鼠中EX诱导的肝脂肪酸氧化增加中肝细胞中eNOS的需求。肝细胞中eNOS的缺失似乎也会损害细胞的能量感知能力，并抑制自噬起始因子ULK 1的活化。这些数据揭示了肝细胞eNOS在运动诱导的肝线粒体适应中的重要和新的作用。
Endothelial nitric oxide synthase (eNOS) is a potential mediator of exercise-induced hepatic mitochondrial adaptations. Here, male and female hepatocyte-specific eNOS knockout (eNOShep−/−) and intact hepatic eNOS (eNOSfl/fl) mice performed voluntary wheel running exercise (EX) or remained in sedentary cage conditions for 10 weeks. EX resolved the exacerbated hepatic steatosis in eNOShep−/− male mice. Elevated H2O2 emission (~50% higher in eNOShep−/− vs eNOSfl/fl mice) was completely ablated with EX. Interestingly, EX increased [1-14C] palmitate oxidation in male eNOSfl/fl, but this was blunted in the eNOShep−/− male mice. eNOShep−/− mice had lower markers of the energy sensors pAMPK/AMPK and mTOR and p-mTOR, and the autophagy initiators ULK1 and pULK1 compared to eNOSfl/fl mice. Females showed elevated ETC protein content and markers of mitochondrial biogenesis (TFAM, pgc1α). Collectively, we demonstrate for the first time the requirement of eNOS in hepatocytes in the EX-induced increases in hepatic fatty acid oxidation in male mice. Deletion of eNOS in hepatocytes also appears to impair the energy sensing ability of the cell and inhibit the activation of the autophagy initiating factor ULK1. These data uncover the important and novel role of hepatocyte eNOS in exercise-induced hepatic mitochondrial adaptations.
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影响因子：
2.4
作者：
Nozaki Y;Fujita K;Wada K;Yoneda M;Shinohara Y;Imajo K;Ogawa Y;Kessoku T;Nakamuta M;Saito S;Masaki N;Nagashima Y;Terauchi Y;Nakajima A
通讯作者：
Nakajima A
DOI：
10.1152/ajpheart.00170.2005
发表时间：
2005-10-01
影响因子：
4.8
作者：
Ojaimi, C;Li, W;Hintze, TH
通讯作者：
Hintze, TH
影响因子：
21.3
作者：
通讯作者：
--
影响因子：
13.5
作者：
Rector, R. Scott;Morris, E. Matthew;Ridenhour, Suzanne;Meers, Grace M.;Hsu, Fong-Fu;Turk, John;Ibdah, Jamal A.
通讯作者：
Ibdah, Jamal A.
DOI：
10.1073/pnas.0405432101
发表时间：
2004-11-23
影响因子：
11.1
作者：
Nisoli, E;Falcone, S;Clementi, E
通讯作者：
Clementi, E