Non-Alcoholic Fatty Liver Disease as a Nexus of Metabolic and Hepatic Diseases

By V. Samuel, Gerald I. Shulman. Cell Metabolism, 2017

657 citations recorded by the source corpus.

NAFLD is closely linked with hepatic insulin resistance. Accumulation of hepatic diacylglycerol activates PKC-ε, impairing insulin receptor activation and insulin-stimulated glycogen synthesis. Peripheral insulin resistance indirectly influences hepatic glucose and lipid metabolism by increasing flux of substrates that promote lipogenesis (glucose and fatty acids) and gluconeogenesis (glycerol, and fatty acid derived acetyl-CoA – an allosteric activator of pyruvate carboxylase). Weight loss with diet or bariatric surgery effectively treats NAFLD, but drugs specifically approved for NAFLD are not available. Some new pharmacological strategies act broadly to alter energy balance or influence pathways that contribute to NAFLD (e.g. agonists for PPAR γ, PPAR α/δ, FXR and analogs for FGF-21, and GLP-1). Others, specifically inhibit key enzymes involved in lipid synthesis (e.g. mitochondrial pyruvate carrier, acetyl-CoA carboxylase, stearoyl-CoA desaturase, monoacyl- and diacyl-glycerol transferases). Finally, a novel class of liver-targeted mitochondrial uncoupling agents increase hepatocellular energy expenditure, reversing the metabolic and hepatic complications of NAFLD.

Subfields: Biochemistry, Endocrinology, Diabetes and Metabolism, Epidemiology

View Paper: https://www.semanticscholar.org/paper/0fa8bb8caae63850caf5ceead5f9288170a0176e

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Biochemistry

1. S. Friedman
2. R. Loomba
3. Gerald I. Shulman

In Endocrinology, Diabetes and Metabolism

1. S. Friedman
2. Gerald I. Shulman
3. R. Loomba

In Epidemiology

1. S. Friedman
2. Gerald I. Shulman
3. R. Loomba
4. Y. Saiman
5. J. Puche
6. J. Bonner
7. D. Clegg
8. B. Palmer

Citations in the corpus

• Mechanisms and disease consequences of nonalcoholic fatty liver disease (2021, background): “Othermetabolic causes of NAFLD andNASH, which are most often genetically related, include (1) defects in intrahepatic lipolysis (e.g., decreased ATGL/CGI-58 activity); (2) defects in triglyceride export (e.g., defective Apo-B 100, MTTP activity); (3) increased glucokinase activity, resulting in incr”
• Membrane Lipid Composition: Effect on Membrane and Organelle Structure, Function and Compartmentalization and Therapeutic Avenues (2019, background): “In fat metabolism, the liver cells break down fats and produce energy (reviewed in [162]).”