2024-03-29T10:31:53Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/78522023-10-13T06:26:32Zcom_20.500.12105_2145com_20.500.12105_2051com_20.500.12105_2144col_20.500.12105_2146
00925njm 22002777a 4500
dc
Manieri, Elisa
author
Herrera-Melle, Leticia
author
Mora, Alfonso
author
Tomas-Loba, Antonia
author
Leiva-Vega, Luis
author
Fernandez, Delia I
author
Rodriguez, Elena
author
Morán, Laura
author
Hernández-Cosido, Lourdes
author
Torres, Jorge L
author
Seoane, Luisa M
author
Cubero, Francisco Javier
author
Marcos, Miguel
author
Sabio, Guadalupe
author
2019-05
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.
J Exp Med. 2019; 216(5):1108-19
0022-1007
http://hdl.handle.net/20.500.12105/7852
30944152
10.1084/jem.20181288
1540-9538
The Journal of experimental medicine
Adiponectin accounts for gender differences in hepatocellular carcinoma incidence