Premium
Trimming the Fat: Acetyl‐CoA Carboxylase Inhibition for the Management of NAFLD
Author(s) -
Imai Norihiro,
Cohen David E.
Publication year - 2018
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.30206
Subject(s) - lipogenesis , lipolysis , medicine , endocrinology , chemistry , white adipose tissue , insulin resistance , fatty acid synthesis , fatty liver , adipose tissue , steatosis , fatty acid , beta oxidation , triglyceride , very low density lipoprotein , biochemistry , biology , lipoprotein , cholesterol , insulin , disease
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. This article is protected by copyright. All rights reserved.