Metabolic Injury of Hepatocytes Promotes Progression of NAFLD and AALD

Raquel Carvalho-Gontijo; Cuijuan Han; Lei Zhang; Vivian Zhang; Mojgan Hosseini; Kristin Mekeel; Bernd Schnabl; Rohit Loomba; Michael Karin; David A. Brenner; Tatiana Kisseleva

doi:10.1055/s-0042-1755316

Seminars in Liver Disease, Table of Contents

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‡^*

¹Department of Medicine, University of California, San Diego School of Medicine, La Jolla, California

²Department of Surgery, University of California, San Diego School of Medicine, La Jolla, California

,

Cuijuan Han‡^*

¹Department of Medicine, University of California, San Diego School of Medicine, La Jolla, California

²Department of Surgery, University of California, San Diego School of Medicine, La Jolla, California

,

Lei Zhang

¹Department of Medicine, University of California, San Diego School of Medicine, La Jolla, California

²Department of Surgery, University of California, San Diego School of Medicine, La Jolla, California

,

Vivian Zhang

¹Department of Medicine, University of California, San Diego School of Medicine, La Jolla, California

²Department of Surgery, University of California, San Diego School of Medicine, La Jolla, California

,

Mojgan Hosseini

³Department of Pathology, University of California, San Diego School of Medicine, La Jolla, California

,

Kristin Mekeel

²Department of Surgery, University of California, San Diego School of Medicine, La Jolla, California

,

Bernd Schnabl

¹Department of Medicine, University of California, San Diego School of Medicine, La Jolla, California

,

Rohit Loomba

¹Department of Medicine, University of California, San Diego School of Medicine, La Jolla, California

,

Michael Karin

⁴Department of Pharmacology, University of California, San Diego School of Medicine, La Jolla, California

,

David A. Brenner

¹Department of Medicine, University of California, San Diego School of Medicine, La Jolla, California

,

Tatiana Kisseleva

²Department of Surgery, University of California, San Diego School of Medicine, La Jolla, California

› Author Affiliations

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

Full Text

References

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