Adiponectin accounts for gender differences in hepatocellular carcinoma incidence.
J Exp Med
; 216(5): 1108-1119, 2019 05 06.
Article
de En
| MEDLINE
| ID: mdl-30944152
ABSTRACT
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.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Calculs biliaires
/
Carcinome hépatocellulaire
/
Adiponectine
/
Tumeurs du foie
Type d'étude:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Aspects:
Determinantes_sociais_saude
Limites:
Animals
/
Female
/
Humans
/
Male
Langue:
En
Journal:
J Exp Med
Année:
2019
Type de document:
Article
Pays d'affiliation:
Espagne