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Semin Liver Dis 2022; 42(03): 233-249
DOI: 10.1055/s-0042-1755316
Review Article

Metabolic Injury of Hepatocytes Promotes Progression of NAFLD and AALD

Raquel Carvalho-Gontijo‡   *
1   Department of Medicine, University of California, San Diego School of Medicine, La Jolla, California
2   Department of Surgery, University of California, San Diego School of Medicine, La Jolla, California
,
Cuijuan Han‡   *
1   Department of Medicine, University of California, San Diego School of Medicine, La Jolla, California
2   Department of Surgery, University of California, San Diego School of Medicine, La Jolla, California
,
Lei Zhang
1   Department of Medicine, University of California, San Diego School of Medicine, La Jolla, California
2   Department of Surgery, University of California, San Diego School of Medicine, La Jolla, California
,
Vivian Zhang
1   Department of Medicine, University of California, San Diego School of Medicine, La Jolla, California
2   Department of Surgery, University of California, San Diego School of Medicine, La Jolla, California
,
Mojgan Hosseini
3   Department of Pathology, University of California, San Diego School of Medicine, La Jolla, California
,
Kristin Mekeel
2   Department of Surgery, University of California, San Diego School of Medicine, La Jolla, California
,
Bernd Schnabl
1   Department of Medicine, University of California, San Diego School of Medicine, La Jolla, California
,
Rohit Loomba
1   Department of Medicine, University of California, San Diego School of Medicine, La Jolla, California
,
Michael Karin
4   Department of Pharmacology, University of California, San Diego School of Medicine, La Jolla, California
,
David A. Brenner
1   Department of Medicine, University of California, San Diego School of Medicine, La Jolla, California
,
Tatiana Kisseleva
2   Department of Surgery, University of California, San Diego School of Medicine, La Jolla, California
› Author Affiliations Funding Supported by the National Institutes of Health: R01DK101737, U01AA022614, R01DK099205, R01DK111866, R01AA028550, P50AA011999, U01AA018663, P30 DK120515, 5U01AA029019, R01DK091183, R01DK09920 (T.K.), P42ES010337 and R44DK115242 (D.A.B.); R01 AA24726, R37 AA020703, U01 AA026939, U01 AA026939–04S1, P30 DK120515 and P50 AA011999 (B.S.). RL receives funding support from NIEHS (5P42ES010337), NCATS (5UL1TR001442), DOD PRCRP (W81XWH-18–2-0026), NIDDK (U01DK061734, R01DK106419, R01DK121378, R01DK124318, P30DK120515), NHLBI (P01HL147835), and NIAAA (U01AA029019).
› Further Information
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Abstract

Nonalcoholic liver disease is a component of metabolic syndrome associated with obesity, insulin resistance, and hyperlipidemia. Excessive alcohol consumption may accelerate the progression of steatosis, steatohepatitis, and fibrosis. While simple steatosis is considered a benign condition, nonalcoholic steatohepatitis with inflammation and fibrosis may progress to cirrhosis, liver failure, and hepatocellular cancer. Studies in rodent experimental models and primary cell cultures have demonstrated several common cellular and molecular mechanisms in the pathogenesis and regression of liver fibrosis. Chronic injury and death of hepatocytes cause the recruitment of myeloid cells, secretion of inflammatory and fibrogenic cytokines, and activation of myofibroblasts, resulting in liver fibrosis. In this review, we discuss the role of metabolically injured hepatocytes in the pathogenesis of nonalcoholic steatohepatitis and alcohol-associated liver disease. Specifically, the role of chemokine production and de novo lipogenesis in the development of steatotic hepatocytes and the pathways of steatosis regulation are discussed.

Keywords

liver fibrosis - steatotic hepatocytes - de novo lipogenesis - endoplasmic reticulum stress - unfolded protein response

* These authors have contributed equally to this work and share first authorship.




Publication History

Article published online:
24 August 2022

© 2022. Thieme. All rights reserved.

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