Uncoupling obesity from cancer: Bromodomain co-regulators that control inflammatory networks

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 obesityassociated cancer.