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Uncoupling Obesity from Cancer: Bromodomain Co-regulators That Control Inflammatory Networks

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Obesity, Inflammation and Cancer

Part of the book series: Energy Balance and Cancer ((EBAC,volume 7))

Abstract

As the epidemic of overweight and obesity spreads, the number of ­individuals at risk for metabolic complications of obesity, including cardiovascular disease, type 2 diabetes, and cancer, is expected to increase. Importantly, the risks of complications are not evenly distributed, because not all obesity is biochemically identical. Here we describe “metabolically healthy obese” humans and animal models that show remarkable protection from insulin resistance and glucose intolerance, despite severe obesity. A hallmark of these patients and animals is their reduced inflammatory profile, which we hypothesize confers protection not only from cardiometabolic risk in obesity but also from obesity-associated cancers. Research is urgently required to investigate the basis for this protection, to identify treatment options and prevention strategies for at-risk populations. We explore novel insights into chromatin-based, transcriptional co-regulator mechanisms that link apparently unrelated diseases, with the idea that certain molecularly targeted strategies could moderate multiple risks in obesity. We voice concern that low socioeconomic status citizens are particularly at risk for cardiometabolic disease and obesity-associated cancer, in part because many such individuals live in inflammatory and obesogenic environments. An integrated and hypothesis-driven approach is needed to study and protect these vulnerable and underserved populations from the rising tide of obesity-associated cancer.

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Acknowledgements 

The authors thank the National Institutes of Health (DK090455, GVD and DK0704192, DJB), the US Centers for Disease Control and Prevention (U48 DP001922, DJB), the American Cancer Society (RSG-05-072-01, GVD), the Leukemia and Lymphoma Society (6023-09, GVD), the Boston University Clinical and Translational Science Institute (UL1-TR000157, GVD), and the Evans Center for Biomedical Research. The authors are members of an Evans Center-sponsored, multidisciplinary research collaborative, entitled “Obesity, Inflammation and Cancer” based at Boston University. GVD is a former Chair of the Basic Science Section of The Obesity Society and gratefully acknowledges the intellectual and financial support of the Society and its demonstrated and ongoing commitment to address the problem of obesity-associated cancer.

The authors report no conflicts of interest.

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Authors and Affiliations

  1. Section of Hematology Oncology, Department of Pharmacology and Experimental Therapeutics and Cancer Research Center, Boston University School of Medicine, 72 East Concord Street, K520, Boston, MA, 02118, USA

    Gerald V. Denis Ph.D.

  2. Department of Community Health Sciences, Boston University School of Public Health, 801 Massachusetts Avenue 4th floor, Boston, MA, 02118, USA

    Deborah J. Bowen Ph.D.

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Correspondence to Gerald V. Denis Ph.D. .

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  1. , Department of Medicine, Weill Cornell Medical College, 525 E. 68th St. Room F-206, New York, 10065, New York, USA

    Andrew J. Dannenberg

  2. School of Medicine, Center for Science, Health & Society, Case Western Reserve University, Euclid Ave. 10900, Cleveland, 44106, Ohio, USA

    Nathan A. Berger

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Denis, G.V., Bowen, D.J. (2013). Uncoupling Obesity from Cancer: Bromodomain Co-regulators That Control Inflammatory Networks. In: Dannenberg, A., Berger, N. (eds) Obesity, Inflammation and Cancer. Energy Balance and Cancer, vol 7. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6819-6_3

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