"The obesity paradox" in disease--is the protective effect of obesity true?

Although obesity and the associated metabolic syndrome negatively impact on health outcomes, a paradoxical relationship between obesity and mortality has been reported for specific patient populations - the "obesity paradox". However, underlying mechanisms remain unclear and several possible explanations are being discussed. First, a true protective effect of obesity is possible, mediated through differences in the immune response and more metabolic reserves. Although there is a growing body of evidence supporting this hypothesis, the influence of obesity on immune function is complex and not completely understood. Second, a statistical bias is possible, owing to confounding, selection bias, performance bias and measurement bias of most observational studies reporting the obesity paradox. Within this article, we summarise current concepts regarding the underlying pathophysiology and possible explanation for the obesity paradox, and discuss open questions such as whether age is an effect modifier on the relationship of obesity and mortality.