2026-06-14T03:33:49Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/78522024-09-27T08:02:16Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

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 10.1084/jem.20181288 1540-9538 0022-1007 The Journal of experimental medicine 30944152 http://hdl.handle.net/20.500.12105/7852 Adiponectin accounts for gender differences in hepatocellular carcinoma incidence