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Mechanisms of Liver Injury in Non-Alcoholic Steatohepatitis

  • Fatty Liver Disease (SA Harrison and J George, Section Editors)
  • Published:
Current Hepatology Reports Aims and scope Submit manuscript

Abstract

Non-alcoholic steatohepatitis (NASH) is a disorder marked by alterations in hepatic lipid homeostasis as well as liver injury in the form of cell death, inflammation and fibrosis. Research into the pathophysiology of NASH is dynamic. New concepts from the fields of cell biology, microbiology, immunology and genetics are being tested for their applicability to NASH; discoveries in each of these areas are enriching our understanding of this complex disease. This review summarizes how recent developments from the bench and bedside are merging with more traditional concepts to reshape our view of NASH pathogenesis. Highlights include human studies that emphasize the role of de novo lipogenesis in NASH and experimental work uncovering a role for the inflammasome in NASH. Genetic predispositions to NASH are being clarified, and intestinal microbiome is emerging as a determinant of fatty liver. These unique ideas are now taking their place within an integrated picture of NASH pathogenesis.

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Abbreviations

ApoB:

apolipoprotein B

ATF6:

activating transcription factor 6

CB2:

cannabinoid receptor 2

CCL2:

C-C chemokine ligand 2

c-Src:

proto-oncogene tyrosine-protein kinase

CYP2E1:

cytochrome P450 2E1

DNL:

de novo lipogenesis

ER:

endoplasmic reticulum

GCKR:

glucokinase regulator

HSC:

hepatic stellate cells

IL-1β:

interleukin-1β

IRE1:

inositol-requiring protein 1

JNK:

Jun N-terminal kinase

LPAAT:

lysophosphatidic acid acyltransferase

LPC:

lysophosphatidylcholine

LYPAL1:

lysophospholipase-like 1

MRC:

mitochondrial respiratory chain

NAFL:

non-alcoholic fatty liver

NASH:

non-alcoholic steatohepatitis

NCAN:

neurocan

NLRP:

NOD-like receptor proteins

NOD:

nucleotide-binding oligomerization domain

PERK:

RNA-dependent protein kinase-like ER kinase

PNPLA3:

patatin-like phospholipase domain-containing 3

PPARδ:

peroxisome proliferator-activated receptor-δ

PPP1R3B:

protein phosphatase 1 regulatory subunit 3B

RANTES:

regulated on activation normal T cell expressed and secreted (CCL5)

ROS:

reactive oxygen species

SFA:

saturated fatty acid

SREBP-1:

sterol regulatory element binding protein-1

TCA:

tricarboxylic acid cycle

TLR:

Toll-like receptor

UPR:

unfolded protein response

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Acknowledgments

The authors are supported by the following grants: T32 DK060414 (CCD), R01 DK068450 (JJM), P30 DK026743 (JJM).

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Caroline C. Duwaerts declares no conflicts of interest.

Jacquelyn J. Maher declares no conflicts of interest.

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This article does not contain any studies with human or animal subjects performed by the authors.

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Duwaerts, C.C., Maher, J.J. Mechanisms of Liver Injury in Non-Alcoholic Steatohepatitis. Curr Hepatology Rep 13, 119–129 (2014). https://doi.org/10.1007/s11901-014-0224-8

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