Hepatic steatosis and VLDL hypersecretion

摘要

As triglyceride accumulation progresses in nonalcoholic fatty liver disease (NAFLD) during development of hepatic insulin resistance, steatosis becomes steatohepatitis which advances to end-stage cirrhosis. The NAFLD epidemic has driven research to define metabolic pathways stimulated by overnutrition. Metabolism of triglyceride by liver is regulated by insulin and dysregulation occurs with insulin resistance involving altered activities of phosphatidylinositide 3-kinases (PI3K), the serine/ threonine kinase thymoma viral proto-oncogene 1 (AKT), mammalian target of rapamycin (TORC), forkhead box O (FoxO) proteins, lipins and sterol regulatory element-binding proteins (SREBP). Liver triglyceride is exported in very-low-density lipo-proteins (VLDLs) and delivered to peripheral tissues. Hepatic overload of triglyceride derived from increased fatty acid (FA) flux, chylomicron and VLDL remnant uptake, and the progressive increase in de-novo lipogenesis (DNL) can be balanced by VLDL secretion. Imbalance diverts FA to oxidative pathways that have the potential to impair liver function.