Elisa Manieri et al discovered that a decrease in a hormone secreted by fat cells is responsible for an increased risk of liver cancer in males. The levels of hormone adiponectin decrease in males during puberty which make them prone to a higher incidence of hepatocellular carcinoma (HCC) than women. HCC risk is also higher among obese individuals during which the body secretes low adiponectin levels. Researchers found that adiponectin protects against liver cancer development through the activation of AMP-activated protein kinase (AMPK) and p38α. The study showed that testosterone in males activates JNK protein (c-Jun N-terminal kinases) in human and mice adipocytes. JNK protein mediates inhibition of adiponectin which results in their lower secretion. The research also showed that genetic deletion of JNK1 in mouse adipose tissue resulted in higher adiponectin levels and protection against HCC. Quantification of circulating adiponectin in mice models detected more than twice the level in females than in males. This correlated with the vigorous growth of subcutaneously implanted mouse HCC-derived tumour cells in males than in females. Gender disparity in HCC was confirmed by subcutaneously injecting colon adenocarcinoma-derived tumour cells or melanoma-derived tumour in male and female mice models which showed no difference in growth patterns. The study unravels the relation between sex hormones and adipocytes signalling clarifying the disparity in liver cancer development.
Source: Journal of Experimental Medicine April 3, 2019 DOI: 10.1084/jem.20181288 http://jem.rupress.org/content/early/2019/04/02/jem.20181288