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Diet-induced obesity and ethanol impair progression of hepatocellular carcinoma in a mouse mesenteric vein injection model.

Diet-induced obesity and ethanol impair progression of hepatocellular carcinoma in a mouse mesenteric vein injection model.

Authors :
Thompson KJ
Swan RZ
Iannitti DA
McKillop IH
Sindram D
Source :
Surgical endoscopy [Surg Endosc] 2013 Jan; Vol. 27 (1), pp. 246-55. Date of Electronic Publication: 2012 Jul 18.
Publication Year :
2013

Abstract

Background: Hepatocellular carcinoma (HCC) is a rapidly increasing cancer whose known risk factors are chronic ethanol abuse, viral hepatitis infection, and aflatoxin exposure. Obesity, an emerging HCC risk factor, is reaching epidemic proportions in developed nations. This study investigated the effects of diet-induced obesity (DIO) and chronic ethanol consumption on HCC progression in mice in vivo.<br />Methods: In this study, C57BL/6 DIO mice and lean litter mates were maintained on a 60% (high-fat diet [HFD]) diet or a 10% (control diet [CD]) kcal% fat diet for 7 weeks before they were weaned to 10/20% ([v/v], alternating days) ethanol in drinking water (EtOH) or maintenance on drinking water (H(2)O) alone. Hepatic tumor formation was initiated by intrahepatic Hepa1-6 cell (6 × 10(6) cells) inoculation 6 weeks later via the mesenteric vein.<br />Results: The animals receiving the HFD showed decreased tumor incidence and area of hepatic foci versus the CD animals maintained on H(2)O alone. The action of EtOH suppressed tumor incidence further in both the CD and the HFD mice. Serologic analysis showed no significant differences in liver enzymes among the groups. Protein analysis demonstrated increased P450 2E1 (CYP2E1) in the groups maintained on EtOH, an effect exacerbated by HFD. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis demonstrated increased tumor necrosis factor-alpha (TNF-α) expression in HFD HCC mice (H(2)O and EtOH) concomitant with decreased transforming growth factor-beta (TGF-β) expression.<br />Conclusions: Although obesity and EtOH consumption are known risk factors for HCC initiation and development, the data in this study suggest that these factors impair progression of established tumors within the liver.

Details

Language :
English
ISSN :
1432-2218
Volume :
27
Issue :
1
Database :
MEDLINE
Journal :
Surgical endoscopy
Publication Type :
Academic Journal
Accession number :
22806512
Full Text :
https://doi.org/10.1007/s00464-012-2429-7