Metabolically healthy obesity and reduced cancer risk

Obesity is associated with increased risks for cancer of the breast, colon and several other organs. Whereas insulin-resistant obesity is recognized as a chronic inflammatory disease, not all obesity is inflammatory; certain ‘metabolically healthy’ obese (MHO) adults preserve normal metabolism, are glucose tolerant and their fat is not inflamed. Several types of cancer can arise through chronic inflammation, leading us to wonder whether the low-inflammatory profile of MHO adults also protects against obesity-associated cancers. There are insufficient epidemiologic data that address 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. We have begun to disentangle these relationships:


Ccmpleted 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 ‘metabolically unhealthy obese’ (MUO), adults. This observation is innovative and important, suggesting that we should not be lumping all high BMI adults together and treating them as one category that influences cancer risk. Some adults are much less inflamed and healthier than others, and enjoy lower risk. New research should identify the factors and signaling pathways that protect these obese adults against cancer, so that protection can be conferred to at-risk obese adults.

Moore et al 2014

These data have led us to hypothesize that reduced inflammation is the root cause of the reduced risk for obesity-associated cancer among MHO adults compared to similarly obese MUO adults.

Denis and Obin 2012

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.

Denis and Bowen 2013

Metabolism also stratifies cardiovascular risk in obesity. Some individuals who are lean but inflamed and metabolically abnormal often exhibit ectopic adipose deposition, or a build up of fat tissue in the wrong places (liver, around the heart and kidneys, in the gut), where it can wreak tremendous metabolic damage.

Denis and Hamilton 2013

Strissel et al 2014

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