Metabolically healthy obesity and reduced cancer risk
Obesity is associated with increased risks for cancer of the breast, colon and several other organs. While insulin-resistant obesity is recognized as a chronic inflammatory disease, not all obesity is inflammatory; certain ‘metabolically healthy’ obese (MHO) subjects preserve normal metabolism, are glucose tolerant and their fat is not inflamed. Certain cancers arise through chronic inflammation, leading us to wonder whether the low-inflammatory profile of MHO subjects also protects against obesity-associated cancers. There are essentially no epidemiologic data addressing the question of whether obesity and other metabolic abnormalities such as insulin resistance or dyslipidemia interact to promote long-term risk of obesity-associated cancers.
Preliminary analysis of Framingham Study adults who are obese and glucose tolerant reveals that that these potentially MHO subjects have much lower risk for obesity-associated cancer compared to obese, glucose intolerant, potentially MUO, subjects. These data have led us to hypothesize that reduced inflammation is the root cause of the reduced risk for obesity-associated cancer among MHO subjects compared to similarly obese MUO subjects.
The lower risk of obesity-associated cancers among MHO adults must be investigated with new research. Based on the above discussion, it is reasonable to hypothesize that specific factors in the low-inflammatory profile of MHO individuals contributes to this protection from cancer, but at present, it is unknown whether the most important factors are locally or systemically reduced TNF-α, IL-6, CRP or other pro-inflammatory cytokines; reduced fasting insulin and fasting glucose; or only mild attenuation of high molecular weight adiponectin in these MHO adults.