Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Cell Metab. 2011 Dec 7;14(6):804-10. doi: 10.1016/j.cmet.2011.11.004.
Approximately one-third of the U.S. population has nonalcoholic fatty liver disease (NAFLD), a condition closely associated with insulin resistance and increased risk of liver injury. Dysregulated mitochondrial metabolism is central in these disorders, but the manner and degree of dysregulation are disputed. This study tested whether humans with NAFLD have abnormal in vivo hepatic mitochondrial metabolism. Subjects with low (3.0%) and high (17%) intrahepatic triglyceride (IHTG) were studied using (2)H and (13)C tracers to evaluate systemic lipolysis, hepatic glucose production, and mitochondrial pathways (TCA cycle, anaplerosis, and ketogenesis). Individuals with NAFLD had 50% higher rates of lipolysis and 30% higher rates of gluconeogenesis. There was a positive correlation between IHTG content and both mitochondrial oxidative and anaplerotic fluxes. These data indicate that mitochondrial oxidative metabolism is ~2-fold greater in those with NAFLD, providing a potential link between IHTG content, oxidative stress, and liver damage.
大约三分之一的美国人口患有非酒精性脂肪性肝病 (NAFLD)，这种疾病与胰岛素抵抗和肝损伤风险增加密切相关。线粒体代谢失调是这些疾病的核心，但失调的方式和程度存在争议。本研究旨在测试患有 NAFLD 的人类是否存在异常的体内肝线粒体代谢。本研究使用 (2)H 和 (13)C 示踪剂研究了肝内甘油三酯 (IHTG) 含量低 (3.0%) 和高 (17%) 的人群，以评估全身脂肪分解、肝葡萄糖生成和线粒体途径 (三羧酸循环、氨甲酰磷酸合成和酮体生成)。NAFLD 患者的脂肪分解率高出 50%，糖异生率高出 30%。IHTG 含量与线粒体氧化和氨甲酰磷酸合成通量呈正相关。这些数据表明，NAFLD 患者的线粒体氧化代谢增加了约 2 倍，为 IHTG 含量、氧化应激和肝损伤之间提供了潜在联系。
