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Abstract Details
Trimming the Fat: Acetyl-CoA Carboxylase Inhibition for the Management of NAFLD
Imai N1, Cohen DE1. Hepatology. 2018 Aug 3. doi: 10.1002/hep.30206. [Epub ahead of print]
Author information
1
Division of Gastroenterology and Hepatology, Joan& Sanford I. Weill Department of Medicine, Weill Cornell Medical College, New York, USA.
Abstract
Nonalcoholic fatty liver disease (NAFLD) is characterized by the hepatic accumulation of excess fatty acids in the form of triglycerides. Normally, the steady state concentration of triglycerides in the liver is low. This is because the accrual of fatty acids due to uptake from the plasma and de novo lipogenesis is balanced by ß-oxidation within liver mitochondria and by secretion into plasma as very low density lipoprotein (VLDL) triglycerides. In the setting of insulin resistance, increased rates of lipolysis within white adipose tissue lead to elevated concentrations of plasma fatty acids and increased rates of uptake into the liver. Insulin resistance also leads to greater rates of hepatic de novo synthesis of fatty acids. Stable isotope studies in human subjects have demonstrated that the majority (~60%) of excess fatty acids originate from white adipose, but the contribution from de novo lipogenesis is substantial (~25%) (1). Because rates of fatty acid oxidation and VLDL secretion are insufficient to compensate, excess fatty acids are sequestered as triglycerides molecules in lipid droplets, which manifest as hepatic steatosis.