Adiponectin accounts for gender differences in hepatocellular carcinoma incidence.
AMP-Activated Protein Kinases
/ metabolism
Adipocytes
/ metabolism
Adiponectin
/ blood
Adipose Tissue
/ metabolism
Animals
Carcinoma, Hepatocellular
/ epidemiology
Cohort Studies
Female
Gallstones
/ blood
Humans
Incidence
Liver
/ metabolism
Liver Neoplasms
/ epidemiology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mitogen-Activated Protein Kinase 14
/ metabolism
Obesity
/ metabolism
Sex Factors
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
06 05 2019
06 05 2019
Historique:
received:
09
07
2018
revised:
11
01
2019
accepted:
08
02
2019
pubmed:
5
4
2019
medline:
6
5
2020
entrez:
5
4
2019
Statut:
ppublish
Résumé
Hepatocellular carcinoma (HCC) is the sixth most common cancer type and the fourth leading cause of cancer-related death. This cancer appears with higher incidence in men and during obesity; however, the specific mechanisms underlying this correlation are unknown. Adipose tissue, a key organ in metabolic syndrome, shows evident gender disparities in the production of adipokines. Levels of the important adipokine adiponectin decrease in men during puberty, as well as in the obese state. Here, we show that this decrease in adiponectin levels is responsible for the increased liver cancer risk in males. We found that testosterone activates the protein JNK in mouse and human adipocytes. JNK-mediated inhibition of adiponectin secretion increases liver cancer cell proliferation, since adiponectin protects against liver cancer development through the activation of AMP-activated protein kinase (AMPK) and p38α. This study provides insight into adipose tissue to liver crosstalk and its gender relation during cancer development, having the potential to guide strategies for new cancer therapeutics.
Identifiants
pubmed: 30944152
pii: jem.20181288
doi: 10.1084/jem.20181288
pmc: PMC6504215
doi:
Substances chimiques
ADIPOQ protein, human
0
Adiponectin
0
Adipoq protein, mouse
0
Mitogen-Activated Protein Kinase 14
EC 2.7.11.24
AMP-Activated Protein Kinases
EC 2.7.11.31
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1108-1119Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2019 Manieri et al.
Références
Curr Opin Lipidol. 2002 Feb;13(1):51-9
pubmed: 11790963
Diabetes. 2002 Sep;51(9):2734-41
pubmed: 12196466
Nat Med. 2002 Nov;8(11):1288-95
pubmed: 12368907
Diabetes. 2003 Feb;52(2):268-76
pubmed: 12540596
J Clin Endocrinol Metab. 2003 Apr;88(4):1730-6
pubmed: 12679465
J Clin Endocrinol Metab. 2004 Aug;89(8):4053-61
pubmed: 15292348
Gastroenterology. 2004 Nov;127(5 Suppl 1):S5-S16
pubmed: 15508102
CA Cancer J Clin. 2005 Mar-Apr;55(2):74-108
pubmed: 15761078
Nat Cell Biol. 2006 May;8(5):516-23
pubmed: 16622416
Diabetes Obes Metab. 2006 May;8(3):264-80
pubmed: 16634986
Mini Rev Med Chem. 2006 Dec;6(12):1331-40
pubmed: 17168809
Nat Genet. 2007 Jun;39(6):741-9
pubmed: 17468757
Science. 2007 Jul 6;317(5834):121-4
pubmed: 17615358
J Hepatol. 2007 Oct;47(4):598-607
pubmed: 17692984
Br J Cancer. 2007 Oct 8;97(7):1005-8
pubmed: 17700568
Lab Invest. 2008 Nov;88(11):1192-203
pubmed: 18794850
Science. 2008 Dec 5;322(5907):1539-43
pubmed: 19056984
Int J Exp Pathol. 2009 Aug;90(4):367-86
pubmed: 19659896
Future Oncol. 2010 Mar;6(3):457-70
pubmed: 20222801
Diabetes Obes Metab. 2010 May;12(5):365-83
pubmed: 20415685
Asian Pac J Cancer Prev. 2009 Dec;10 Suppl:87-90
pubmed: 20553088
Hepatology. 2010 Nov;52(5):1713-22
pubmed: 20941777
Int J Cancer. 2011 Nov 1;129(9):2226-35
pubmed: 21170963
Endocr Rev. 2012 Aug;33(4):547-94
pubmed: 22547160
Gut. 2013 Apr;62(4):606-15
pubmed: 22773548
Mol Oncol. 2013 Apr;7(2):206-23
pubmed: 23428636
Adipocyte. 2013 Jul 1;2(3):128-34
pubmed: 23991358
J Mol Endocrinol. 2015 Oct;55(2):R11-22
pubmed: 26363062
Nat Rev Cancer. 2015 Nov;15(11):653-67
pubmed: 26493646
J Mol Cell Biol. 2016 Apr;8(2):93-100
pubmed: 26993047
Oncotarget. 2016 Oct 4;7(40):66202-66211
pubmed: 27494848
Front Genet. 2016 Sep 20;7:168
pubmed: 27703473
CA Cancer J Clin. 2018 Nov;68(6):394-424
pubmed: 30207593
Hepatology. 1998 Feb;27(2):383-91
pubmed: 9462635