New insights into understanding obesity: from measures to mechanisms

Abstract

Associations between obesity and health are unequivocal and coupled with a substantial body of evidence suggesting that associations are likely causal. These associations and the supporting causal evidence are useful, but hide both the inadequacies of the measures used to qualify obesity and the mechanisms that are responsible for the observable relationships. A challenge therefore remains to determine both the intermediate factors associated with obesity and the mechanisms responsible for connecting excess adiposity (the defining feature of obesity) and health. A growing collection of detailed measures including examples in genomics, proteomics, metabolomics, and the microbiome are now available, allowing a broad approach to characterising obesity and analysing the associations between excess adiposity and health—but to what extent do these associations also provide insight into mechanism? In this specialist review, the problems facing the analysis of obesity (and related measures) both as a disease and as a risk factor for many downstream health outcomes are explored. This review looks to shift focus away from mechanisms of obesity and towards a useful interpretation of mechanisms associated with obesity in the context of promising developments in causal epidemiology.