Current Hepatology Reports

, Volume 13, Issue 2, pp 119–129

Mechanisms of Liver Injury in Non-Alcoholic Steatohepatitis

Fatty Liver Disease (SA Harrison and J George, Section Editors)

DOI: 10.1007/s11901-014-0224-8

Cite this article as:
Duwaerts, C.C. & Maher, J.J. Curr Hepatology Rep (2014) 13: 119. doi:10.1007/s11901-014-0224-8
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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.

Keywords

SteatosisLipogenesisLipolysisLipotoxicityER stressOxidative stressInflammasomeKupffer cellGeneticsAdiponutrinMicrobiome

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

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Liver Center and Department of MedicineUniversity of California, San FranciscoSan FranciscoUSA
  2. 2.San FranciscoUSA