NDLI: High molecular weight adiponectin inhibits proliferation of hepatic stellate cells via activation of adenosine monophosphate-activated protein kinase.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Adachi, Masayuki Brenner, David A.
Description	Country affiliation: United States Author Affiliation: Adachi M ( Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.)
Abstract	UNLABELLED: Adiponectin is an adipocyte-derived, antidiabetic, antiatherogenic adipocytokine that is present in serum as 3 isoforms. Decreased plasma adiponectin levels are closely associated with the severity of nonalcoholic fatty liver diseases. This study was designed to elucidate a role of adiponectin and its mediator adenosine monophosphate-activated protein kinase (AMPK) on proliferation of activated hepatic stellate cells (HSCs), the key cells promoting fibrosis. Immortalized human HSC line hTERT and primary rat HSCs were stimulated with platelet-derived growth factor (PDGF) with or without pretreatment with AMPK activator 5-aminoimidazole-4-carboxamide-1-4-ribofuranoside (AICAR), metformin, or high molecular weight (HMW) adiponectin. HMW adiponectin dose-dependently suppressed PDGF-induced HSC proliferation. Adenoviral transduction with dominant-negative AMPK (DN-AMPK) abolished the suppressive effect of adiponectin in HSCs. AICAR, metformin, or transduction of constitutively active AMPK attenuated PDGF-induced [(3)H]thymidine incorporation, which was abolished by either a chemical AMPK inhibitor or transduction of DN-AMPK, consistent with an antiproliferative effect of AMPK. The suppressive effect of AMPK on HSC proliferation is mediated through multiple mechanisms, including (1) an inhibition of the AKT pathway, (2) inhibition of NADPH oxidase-dependent reactive oxygen species (ROS) production via induction of antioxidant enzymes, and (3) an increase in the expression of the cyclin-dependent kinase inhibitors p27(kip1) and p21(cip1). CONCLUSION: Adiponectin inhibits HSC proliferation via activation of AMPK. AMPK activation by AICAR or metformin inhibits HSC proliferation via suppression of ROS production and subsequent inhibition of AKT pathway. Thus, adiponectin and AMPK inhibit HSC proliferation and hepatic fibrosis via multiple molecular mechanisms.
File Format	HTM / HTML
ISSN	02709139
Issue Number	2
Volume Number	47
e-ISSN	15273350
Journal	Hepatology
Language	English
Publisher	Wiley
Publisher Date	2008-02-01
Publisher Place	United States
Access Restriction	Subscribed
Subject Keyword	Discipline Hepatology Adenylate Kinase Metabolism Adiponectin Pharmacology Cell Division Drug Effects Liver Cytology Genetics Aminoimidazole Carboxamide Analogs & Derivatives Animals Cell Line Enzyme Activation Humans Enzymology Metformin Rna, Messenger Rats Reverse Transcriptase Polymerase Chain Reaction Ribonucleotides Telomerase Journal Article Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Hepatology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in