Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression

By E. Park, J. H. Lee, Guann‐Yi Yu, Guobin He, S. R. Ali, Ryan G. Holzer, C. Österreicher, Hiroyuki Takahashi, M. Karin. Cell, 2010

1,779 citations recorded by the source corpus.

Summary 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 amongst 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.

Subfields: Cardiology and Cardiovascular Medicine, Epidemiology

View Paper: https://www.semanticscholar.org/paper/71d9848942a7b2b4ef078313269c923966dc712f

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In Cardiology and Cardiovascular Medicine

In Epidemiology

Citations in the corpus

Natural forms of vitamin E: metabolism, antioxidant and anti-inflammatory activities and the role in disease prevention and therapy (2014, neutral): “For instance, IL-6 secreted from stimulated macrophages is a proinflammatory cytokine and contributes to arthritis, cancer, and obesity-related promotion of carcinogenesis [83,84].”
Hepatocellular carcinoma in non-alcoholic fatty liver disease: an emerging menace. (2012, background): “The role of adipose-derived TNF and IL-6 in the development of HCC has recently been demonstrated in an experimental model where either dietary or genetic obesity strongly promoted malignant liver tumor growth induced by diethyl nitrosamine in mice if production of these cytokines and their key onco”
Evolution of inflammation in nonalcoholic fatty liver disease: The multiple parallel hits hypothesis (2010, background): “Park and colleagues recently demonstrated that these two cytokines play a central role in the promotion of liver inflammation and tumorigenesis in dietary and genetic obesity.(81) In their studies, obesity-related liver tumor development was dependent on enhanced production of the tumor-promoting cy”
Signaling in innate immunity and inflammation. (2012, background): “Finally, IL6 or TNF-R1 deficiency protects obese mice from hepatocellular carcinomas that form in response to the pro-carcinogen diethylnitrosamine by limiting lipid accumulation and inflammatory infiltrates in the liver (Park et al. 2010).”
The interaction of hepatic lipid and glucose metabolism in liver diseases. (2012, background): “TNF and IL-6 signaling is also involved in the activation of the JAK/STAT and ERK pathways; both mediators are crucial for the development of obesity induced-HCC in a rodent model [126].”
MASLD: a systemic metabolic disorder with cardiovascular and malignant complications (2024, background): “82 This effect was driven by the transcription factor signal transducer and activator of transcription 3 (STAT3) and NF-k B. 83 Interestingly, specific liver cancer progenitor cells in the liver may progress towards a malignant phenotype in an IL- 6-dependent manner.”
NF-κB in the liver—linking injury, fibrosis and hepatocellular carcinoma (2011, background): “There is a strong increase in HCC in both genetic and chemical models of HC”
Immunity, Inflammation, and Cancer (2010, neutral): “Likewise, obesity, whose prevalence is growing at an alarming rate, promotes tumorigenesis in the liver (Park et al., 2010) and pancreas (Khasawneh et al.”