High Intrinsic Aerobic Capacity Protects against Ethanol-Induced Hepatic Injury and Metabolic Dysfunction: Study Using High Capacity Runner Rat Model.
High Intrinsic Aerobic Capacity Protects against Ethanol-Induced Hepatic Injury and Metabolic Dysfunction: Study Using High Capacity Runner Rat Model.
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DOI：
10.3390/biom5043295
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发表时间：
2015-11-20
期刊：
影响因子：
5.5
通讯作者：
Ibdah JA
中科院分区：
文献类型：
--
作者：
Szary N;Rector RS;Uptergrove GM;Ridenhour SE;Shukla SD;Thyfault JP;Koch LG;Britton SL;Ibdah JA
经过几代人为选择的具有高内在耐力/有氧能力的大鼠被开发为高能力跑步者（HCR），以研究高有氧适能与代谢疾病保护之间的联系（Wisloff 等人，Science，2005）。我们之前已经证明 HCR 菌株具有升高的肝线粒体含量和氧化能力。在这项研究中，我们测试了 HCR 大鼠中肝线粒体含量升高是否能够提供“代谢保护”，防止慢性乙醇诱导的肝脂肪变性和损伤。 14 至 20 周龄的 HCR 大鼠（每组 n = 8 只）接受含乙醇（7% v/v；HCR-E）和不含乙醇（HCR-C）的 Leiber-Decarli 液体饮食，体重匹配并配对喂养，以确保等热量摄入。与 HCR-C 相比，HCR-E 中的肝脏甘油三酯 (TG) 含量以及大泡和微泡脂肪变性显着更高 (p < 0.05)。此外，HCR-E 大鼠的肝脏超氧化物歧化酶活性和谷胱甘肽水平显着降低（p < 0.05）。这种肝脏表型还与 HCR-E 动物中总肝脂肪酸氧化 (p = 0.03) 和 β-羟酰基辅酶 A 脱氢酶活性 (p = 0.01) 的减少以及微粒体甘油三酯转移蛋白和 apoB-100 蛋白含量的减少 (p = 0.01) 相关。然而，尽管有这些记录的肝脏改变，乙醇摄入未能引起显着的肝损伤，包括肝脏炎症或血清丙氨酸氨基转移酶（ALT）、游离脂肪酸（FFA）、甘油三酯（TG）、胰岛素或葡萄糖没有变化。在高有氧能力大鼠模型中，高内在有氧适能并不能减少乙醇诱导的肝脂肪变性，但可以防止乙醇诱导的肝损伤和全身代谢功能障碍。
Rats artificially selected over several generations for high intrinsic endurance/aerobic capacity resulting in high capacity runners (HCR) has been developed to study the links between high aerobic fitness and protection from metabolic diseases (Wisloff et al., Science, 2005). We have previously shown that the HCR strain have elevated hepatic mitochondrial content and oxidative capacity. In this study, we tested if the elevated hepatic mitochondrial content in the HCR rat would provide “metabolic protection” from chronic ethanol-induced hepatic steatosis and injury. The Leiber-Decarli liquid diet with ethanol (7% v/v; HCR-E) and without (HCR-C) was given to HCR rats (n = 8 per group) from 14 to 20 weeks of age that were weight matched and pair-fed to assure isocaloric intake. Hepatic triglyceride (TG) content and macro- and microvesicular steatosis were significantly greater in HCR-E compared with HCR-C (p < 0.05). In addition, hepatic superoxide dismutase activity and glutathione levels were significantly (p < 0.05) reduced in the HCR-E rats. This hepatic phenotype also was associated with reduced total hepatic fatty acid oxidation (p = 0.03) and β-hydroxyacyl-CoA dehydrogenase activity (p = 0.01), and reductions in microsomal triglyceride transfer protein and apoB-100 protein content (p = 0.01) in HCR-E animals. However, despite these documented hepatic alterations, ethanol ingestion failed to induce significant hepatic liver injury, including no changes in hepatic inflammation, or serum alanine amino transferase (ALTs), free fatty acids (FFAs), triglycerides (TGs), insulin, or glucose. High intrinsic aerobic fitness did not reduce ethanol-induced hepatic steatosis, but protected against ethanol-induced hepatic injury and systemic metabolic dysfunction in a high aerobic capacity rat model.