Walker, S.L., George, J., and Hebbard, L. (2010) Adiponectin loss is associated with increased hepatocellular carcinoma growth. Journal of Gastroenterology and Hepatology, 25 (Suppl. 3). A72-A72.

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Abstract

Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide and the fastest growing incident cancer in Australia. Most HCCs appear in cirrhotic livers and it is known that overweight and obesity are independent risk factors for progression to cirrhosis and cancer. The mechanisms for this association are unclear. Adiponectin, a protein secreted by adipose tissue, is reduced in obesity and low levels are associated with progression of non-alcoholic steatohepatitis (NASH) and with increased inflammation. The aim of our study was to investigate the role of adiponectin in HCC progression.

Methods Hepatocellular carcinoma was induced in adiponectin knockout and wild type mice at day 15 with a single injection of the chemical carcinogen, diethylnitrosamine 25 mg/kg (DEN). At monthly time-points from 3 to 9 months after injection, mice from each genotype and gender were euthanased and examined for any obvious metastasis, the livers weighed and macroscopically assessed for tumour growth. Paraffin embedded livers and lungs were sectioned and stained with haematoxylin and eosin and examined for pathology changes. Tumour incidence (>0.5 mm) and dimensions were measured and total tumour volume estimated.

Results At 9 months after DEN treatment, male wild-type mice presented with small tumours, whereas adiponectin knockout mice had livers laden with tumours. Tumour volume was approximately nine times greater in adiponectin null than in wild-type mice (adiponectin null 455 ± 199 mm3, n = 10; wild-type, 51 ± 26 mm3, n = 12; p = 0.0392). There was no quantitative difference in the number of tumours per mouse between groups. No statistical difference in tumour size or number was recorded between groups of female mice.

Conclusions Adiponectin null mice when exposed to hepatic carcinogens are more susceptible to develop tumours that phenotypically demonstrate a proliferative advantage. This observation may in part explain the increased risk of HCC in association with overweight and obesity and concomitant low adiponectin levels. We are now investigating the molecular mechanisms whereby the absence of adiponectin leads to more aggressive HCC.

Item ID:	86244
Item Type:	Article (Abstract)
ISSN:	1440-1746
Copyright Information:	© 2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.
Date Deposited:	22 Jul 2025 00:00
FoR Codes:	32 BIOMEDICAL AND CLINICAL SCIENCES > 3202 Clinical sciences > 320209 Gastroenterology and hepatology @ 100%
SEO Codes:	20 HEALTH > 2001 Clinical health > 200101 Diagnosis of human diseases and conditions @ 100%
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