MITOCHONDRIAL ABNORMALITIES IN NAFL ? NONALCOHOLIC FATTY LIVER

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 摘要： 线粒体功能障碍似乎在脂肪肝中起关键作用。 这种形式的肝脏疾病（通常称为NASH或NAFL）由于肥胖和糖尿病的患病率不断增加而达到流行病的比例。在功能上，脂肪肝在体外通过生化测试和在体内通过MR Spec减少ATP，降低ETC复合物的表达，增加解偶联蛋白的表达，并且在这些肝脏中细胞凋亡增加。形态学上，通过TEM，线粒体通常是肿胀的，并含有结晶内含物，其似乎与嵴连续，表明构象变化。它们与植物黄化体的相似性进一步表明了脂双层异常形成的共同起源。 这些形式的存在与脂质过氧化的指数相关，但不与光镜损伤的程度相关，这表明这些可能是氧化应激的适应机制。三维电磁成像可以提供额外的线索，这些结构的起源，这可能会提供更好地了解NAFL的发病机制和最佳治疗。也可能涉及相关的神经退行性疾病和肝细胞癌，通常包含脂肪变性区域。 我打算利用这些数据向NIH和其他来源申请额外的资金。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. ABSTRACT: Mitochondrial dysfunction appears to play a key role in fatty liver. This form of liver disease (commonly referred to as NASH or NAFL) is reaching epidemic proportions due to the increasing prevalence of obesity and diabetes. Functionally, the fatty liver has diminished ATP in vitro by biochemical tests and in vivo by MR Spec, decreased expression of ETC complexes, increased expression of uncoupling protein, and apoptosis is increased in these livers. Morphologically, by TEM the mitochondria are commonly swollen and contain crystalline inclusions which appear to be in continuity with the cristae suggesting a conformational change. Their resemblance to plant etioplasts further suggest a common origin in abnormal formation of a lipid bilayer. The presence of these forms correlates to indices of lipid peroxidation but not to the degree of light microscopic injury suggesting that these may serve as an adaptive mechanism to oxidative stress. Three-dimensional EM imaging may provide additional clues to the origin of these structures and this may provide better understanding of the pathogenesis of NAFL and its optimal therapy. There may also be implications for associated neurodegenerative diseases and hepatocellular cancer which commonly contains areas of steatosis. It is my intention to use this data to apply for NIH and other sources for additional funding.