Mechanisms of Hepatic Triglyceride Accumulation in Nonalcoholic Fatty Liver Disease
By Y. Kawano, D. Cohen. Journal of gastroenterology, 2013
918 citations recorded by the source corpus.
Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation in the absence of excess alcohol intake. NAFLD is the most common chronic liver disease, and ongoing research efforts are focused on understanding the underlying pathobiology of hepatic steatosis with the anticipation that these efforts will identify novel therapeutic targets. Under physiological conditions, the low steady-state triglyceride concentrations in the liver are attributable to a precise balance between acquisition by uptake of non-esterified fatty acids from the plasma and by de novo lipogenesis, versus triglyceride disposal by fatty acid oxidation and by the secretion of triglyceride-rich lipoproteins. In NAFLD patients, insulin resistance leads to hepatic steatosis by multiple mechanisms. Greater uptake rates of plasma non-esterified fatty acids are attributable to increased release from an expanded mass of adipose tissue as a consequence of diminished insulin responsiveness. Hyperinsulinemia promotes the transcriptional upregulation of genes that promote de novo lipogenesis in the liver. Increased hepatic lipid accumulation is not offset by fatty acid oxidation or by increased secretion rates of triglyceride-rich lipoproteins. This review discusses the molecular mechanisms by which hepatic triglyceride homeostasis is achieved under normal conditions, as well as the metabolic alterations that occur in the setting of insulin resistance and contribute to the pathogenesis of NAFLD.
Subfields: Biochemistry, Endocrinology, Diabetes and Metabolism, Epidemiology
View Paper: https://www.semanticscholar.org/paper/fae824338b7e5a78bf832ccdeaaea599304261d4
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Citations in the corpus
- Role of Dietary Fructose and Hepatic de novo Lipogenesis in Fatty Liver Disease (2016, background): “Palmitate (C16:0) is the primary fatty acid synthesized endogenously (reviewed in [29]), but it may be elongated to the 18-carbon fatty acid stearate or to longer fatty acids by the enzyme elongation of very long-chain fatty acids protein 6 (ELOVL6).”
- Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease (2018, background): “The nascent VLDL particle is then transferred to the Golgi apparatus, and during this process, the particle is further lipidated until a mature VLDL particle is formed [111].”
- Triglyceride metabolism in the liver (2017, neutral): “Moreover, Them2-deficiency results in diminished expression of PPAR α and HNF4 α , possibly due to the role of this enzyme in the control of FA ligands of these nuclear receptors (53) and the reduced FA oxidation (135).”