Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression.
Epidemiological studies indicate that overweight and obesity are associated with increased cancer risk. To study how obesity augments cancer risk and development, we focused on hepatocellular carcinoma (HCC), the common form of liver cancer whose occurrence and progression are the most strongly affected by obesity among all cancers. We now demonstrate that either dietary or genetic obesity is a potent bona fide liver tumor promoter in mice. Obesity-promoted HCC development was dependent on enhanced production of the tumor-promoting cytokines IL-6 and TNF, which cause hepatic inflammation and activation of the oncogenic transcription factor STAT3. The chronic inflammatory response caused by obesity and enhanced production of IL-6 and TNF may also increase the risk of other cancers.
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Eek Joong
EJ
Park
Jun Hee
JH
Lee
Guann-Yi
GY
Yu
Guobin
G
He
Syed Raza
SR
Ali
Ryan G
RG
Holzer
Christoph H
CH
Osterreicher
Hiroyuki
H
Takahashi
Michael
M
Karin
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000209:etiology / Q000276:immunology*; D049109:Cell Proliferation; D004052:Diethylnitrosamine; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006505:Hepatitis / Q000209:etiology / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology*; D008113:Liver Neoplasms / Q000139:chemically induced / Q000209:etiology / Q000276:immunology*; D008297:Male; D051379:Mice; D009765:Obesity / Q000150:complications / Q000276:immunology*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D004052:Diethylnitrosamine; D048049:Extracellular Signal-Regulated MAP Kinases