Obesity and metabolic disease: is adipose tissue the culprit?

Abstract

Obesity is a risk factor for the development of type 2 diabetes and CVD. Is adipose tissue the culprit in the relationship between obesity and metabolic disease? It is certainly possible to argue that adipose tissue function is disturbed in obesity in such a way that adverse consequences may follow. For instance, lipolysis is down regulated, the sensitivity of lipolysis to insulin is reduced and there are disturbances in the regulation of adipose tissue blood flow. However, when examined critically these changes can be seen as adaptations to the increased adipose tissue mass, making the situation better rather than worse. In terms of the many peptide and other factors now known to be secreted from adipose tissue, it is easier to argue that adipose tissue is the culprit. However, for no single 'adipokine' is there as yet unequivocal evidence of a link between adipose tissue secretion and adverse metabolic events in other tissues. The best documented of these adipokines in relation to insulin resistance is adiponectin. Here, unusually, adiponectin confers insulin sensitivity, and its secretion is down regulated in obesity. It could be again that adipose tissue has down regulated its function in an attempt to compensate for its increased mass, although certainly that down-regulation is too extreme. On balance, it is clear that adipose tissue is a link in the chain of events leading to metabolic disease, but in many respects it is an innocent intermediary trying to deal with the consequences of positive energy balance, the real culprit.