@article{c86ae880fc7c477687af2bda11f37ccb,
title = "Mechanisms and disease consequences of nonalcoholic fatty liver disease",
abstract = "Nonalcoholic fatty liver disease (NAFLD) is the leading chronic liver disease worldwide. Its more advanced subtype, nonalcoholic steatohepatitis (NASH), connotes progressive liver injury that can lead to cirrhosis and hepatocellular carcinoma. Here we provide an in-depth discussion of the underlying pathogenetic mechanisms that lead to progressive liver injury, including the metabolic origins of NAFLD, the effect of NAFLD on hepatic glucose and lipid metabolism, bile acid toxicity, macrophage dysfunction, and hepatic stellate cell activation, and consider the role of genetic, epigenetic, and environmental factors that promote fibrosis progression and risk of hepatocellular carcinoma in NASH.",
keywords = "fibrosis, insulin resistance, lipotoxicity, liver cancer, metabolism-associated fatty liver disease, nonalcoholic steatohepatitis",
author = "Rohit Loomba and Friedman, {Scott L.} and Shulman, {Gerald I.}",
note = "Funding Information: The authors received funding support from the Department of Health and Human Services (NIH/NIDDK/NHLBI/NIEHS/NCATS): R01 DK56621 and DK128289 (to S.L.F.); R01 DK113984, R01 DK114793, R01 DK116774, R01 DK119968, RC2 DK120534, and P30 DK045735 (to G.I.S.); and P42 ES01033, UL1 TR001442, U01 DK061734, R01 DK106419, R01 DK121378, R01 DK124318, P30 DK120515, and P01 HL147835 (to R.L.). R.L. S.L.F. and G.I.S. wrote the manuscript and read and approved the final version of the manuscript. R.L. serves as a consultant for Anylam/Regeneron, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Bristol Myers Squibb, CohBar, Eli Lilly, Galmed, Gilead, Glympse bio, Inipharm, Intercept, Ionis, Janssen, Madrigal, Metacrine, NGM Biopharmaceuticals, Novartis, Novo Nordisk, Pfizer, Sagimet, 89 bio, and Viking Therapeutics. In addition, his institution has received grant support from Allergan, Astrazeneca, Boehringer-Ingelheim, Bristol Myers Squibb, Eli Lilly, Galectin Therapeutics, Galmed Pharmaceuticals, Genfit, Gilead, Intercept, Inventiva, Janssen, Madrigal Pharmaceuticals, Merck, NGM Biopharmaceuticals, Pfizer, and Siemens. He is also co-founder of Liponexus; S.L.F. is a consultant to 89 Bio, Amgen, Axcella Health, Blade Therapeutics, Bristol Myers Squibb, Can-Fite Biopharma, Casma Therapeutics, ChemomAb, Escient Pharmaceuticals, Forbion, Galmed, Gordian Biotechnology, Glycotest, Glympse Bio, In sitro, Morphic Therapeutics, North Sea Therapeutics, Novartis, Ono Pharmaceuticals, Pfizer Pharmaceuticals, Scholar Rock, and Surrozen and has stock options (all less than 1% of company value) in Blade Therapeutics, Escient, Galectin, Galmed, Genfit, Glympse, Hepgene, Lifemax, Metacrine, Morphic Therapeutics, Nimbus, North Sea Therapeutics, Scholar Rock, and Surrozen. G.I.S. serves on the scientific advisory boards for Merck, Novo Nordisk, AstraZeneca, Gilead Sciences, Esperion, Generian, Levels, 89bio, and Janseen Research and Development. G.I.S. receives investigator-initiated support from AstraZeneca, Gilead Sciences, and Merck. G.I.S. is an inventor on Yale patents for liver-targeted mitochondrial uncoupling agents and controlled-release mitochondrial uncoupling agents for the treatment of NAFLD, NASH, T2D, and related metabolic disorders and is a scientific-cofounder of TLC. Funding Information: The authors received funding support from the Department of Health and Human Services (NIH/NIDDK/NHLBI/NIEHS/NCATS) : R01 DK56621 and DK128289 (to S.L.F.); R01 DK113984 , R01 DK114793 , R01 DK116774 , R01 DK119968 , RC2 DK120534 , and P30 DK045735 (to G.I.S.); and P42 ES01033 , UL1 TR001442 , U01 DK061734 , R01 DK106419 , R01 DK121378 , R01 DK124318 , P30 DK120515 , and P01 HL147835 (to R.L.). Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = may,
day = "13",
doi = "10.1016/j.cell.2021.04.015",
language = "English",
volume = "184",
pages = "2537--2564",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "10",
}