The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Inflammation and mitochondrial fatty acid β-oxidation link obesity to early tumor promotion
Open accessAbstract
Obesity is associated with increased risk for developing pancreatic cancer, and it is suggested that insulin resistance provides the missing link. Here we demonstrate that under the context of genetic susceptibility, a high fat diet (HFD) predisposes mice with oncogenic K-ras activation to accelerated pancreatic intraepithelial neoplasm (PanIN) development. Tumor promotion is closely associated with increased inflammation and abrogation of TNFR1 signaling significantly blocks this process underlining a central role for TNFα in obesity-mediated enhancement of PanIN lesions. Interestingly, however, despite increased TNFα levels, mice remain insulin sensitive. We show that, while aggravating tumor promotion, a HFD exerts dramatic changes in energy metabolism through enhancement of pancreatic exocrine insufficiency, metabolic rates, and expression of genes involved in mitochondrial fatty acid (FA) β-oxidation that collectively contribute to improved glucose tolerance in these mice. While on one hand these findings provide significant evidence that obesity is linked to tumor promotion in the pancreas, on the other it suggests alterations in inflammatory responses and bioenergetic pathways as the potential underlying cause.
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Cites
Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. Adults
Calle, E. E., Rodriguez, C., Walker-Thurmond, K., & Thun, M. J. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa021423 · Cited by 7,696
TLR4 links innate immunity and fatty acid-induced insulin resistance
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IKKβ Links Inflammation and Tumorigenesis in a Mouse Model of Colitis-Associated Cancer
Greten, F. R., Eckmann, L., Greten, T. F., Park, J. M., Li, Z.-W., Egan, L. J., Kagnoff, M. F., & Karin, M. (2004) · Cell · doi:10.1016/j.cell.2004.07.013 · Cited by 2,433
Self-citationProtection from obesity-induced insulin resistance in mice lacking TNF-α function
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IKK-β links inflammation to obesity-induced insulin resistance
Arkan, M. C., Hevener, A. L., Greten, F. R., Maeda, S., Li, Z.-W., Long, J. M., Wynshaw-Boris, A., Poli, G., Olefsky, J., & Karin, M. (2005) · Nature Medicine · doi:10.1038/nm1185 · Cited by 1,773
Self-citationMechanism of free fatty acid-induced insulin resistance in humans.
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Self-citationNF-κB, inflammation, immunity and cancer: coming of age
Taniguchi, K., & Karin, M. (2018) · Nature Reviews Immunology · doi:10.1038/nri.2017.142 · Cited by 2,679
Bensaad, K., Favaro, E., Lewis, C. A., Peck, B., Lord, S., Collins, J. M., Pinnick, K. E., Wigfield, S., Buffa, F. M., Li, J.-L., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.08.056 · Cited by 665
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Metadata
- Authors
- Khasawneh, J., Schulz, M. D., Walch, A., Rozman, J., de Angelis, M. H., Klingenspor, M., Buck, A., Schwaiger, M., Saur, D., Schmid, R. M., Klöppel, G., Sipos, B., Greten, F. R., & Arkan, M. C.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2009-03-03
- Volume
- 106
- Issue
- 9
- Pages
- 3354-3359
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1994987533
- Cited by
- 182
- References
- 6
- FWCI
- 3.79
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Inflammation and mitochondrial fatty acid β-oxidation link obesity to early tumor promotion. https://app.cochat.ai/papers/10.1073/pnas.0802864106
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- Khasawneh, J., Schulz, M. D., Walch, A., Rozman, J., de Angelis, M. H., Klingenspor, M., Buck, A., Schwaiger, M., Saur, D., Schmid, R. M., Klöppel, G., Sipos, B., Greten, F. R., & Arkan, M. C. (2009). Inflammation and mitochondrial fatty acid β-oxidation link obesity to early tumor promotion. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0802864106
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
