Dataset Information

Adiponectin accounts for gender differences in hepatocellular carcinoma incidence.

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 p38?. 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.

SUBMITTER: Manieri E

PROVIDER: S-EPMC6504215 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Adiponectin accounts for gender differences in hepatocellular carcinoma incidence.

Manieri Elisa E Herrera-Melle Leticia L Mora Alfonso A Tomás-Loba Antonia A Leiva-Vega Luis L Fernández Delia I DI Rodríguez Elena E Morán Laura L Hernández-Cosido Lourdes L Torres Jorge L JL Seoane Luisa M LM Cubero Francisco Javier FJ Marcos Miguel M Sabio Guadalupe G

The Journal of experimental medicine 20190403 5

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 ...[more]

PMID: 30944152

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Project description:BACKGROUND:Numerous studies associate adipokines with colorectal malignancy, but few data deal with patients suffering exclusively of rectal carcinoma (RC). AIMS:We evaluated leptin and adiponectin levels in RC patients compared to healthy population and their dynamics after surgery. MATERIAL AND METHODS:Serum leptin and adiponectin were evaluated before surgery in 59 RC consecutive patients (38 males and 21 females), and in age and weight matched healthy controls. Measurements were repeated at 24, 72 hours and 7 days after surgery. RESULTS:Adipokine levels were higher in women. Controls had higher leptin (32.±4.34 vs 9.51±1.73 ng/ml in women and 11±2.66 vs 2.54±0.39 ng/ml in men, p = 0.00048 and 0.0032) and lower adiponectin (9±0.64 vs 11.85±1.02 ?g/ml in women and 7.39±0.51 vs 8.5±0.62 ?g/ml in men, p = 0.017 and 0.019) than RC patients. Surgery caused an increase of leptin from 5.11±0.8 to 18.7±2.42 ng/ml, p = 6.85 x 10¨8, and a decrease of adiponectin from 9.71±0.58 to 7.87±0.47 ?g/ml, p = 1.4 x 10¨10 for all RC patients and returned thereafter to the initial range at 7 days. Adipokines were correlated with body weight (BW). The significance of correlation persisted after surgery only in males, but disappeared in females. Adipokines were not modified by tumor position, presurgical chemoradiotherapy or surgical technique. Women with RC experiencing weight loss had higher adiponectin than women without weight modifications (p<0.05 at all time points). CONCLUSIONS:Adipokine levels of patients with RC differ from the healthy population, possibly reflecting an adaptation to disease. Adipokine modifications after surgery may be related to acute surgical stress. Whether leptin and adiponectin directly interact is not clear. Women have higher adipokine levels, more so after significant weight loss, but the strength of their correlation with BW decreases after surgery. These data suggest gender differences in the adipokine profile of RC patients which may find clinical applications.

Dataset Information

Adiponectin accounts for gender differences in hepatocellular carcinoma incidence.

Publications

Adiponectin accounts for gender differences in hepatocellular carcinoma incidence.

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