The Sir David Cuthbertson Medal Lecture. Hunting for new pieces to the complex puzzle of obesity

Abstract

Disentangling the neuroendocrine systems that regulate energy homeostasis and adiposity has been a long-standing challenge in pathophysiology, with obesity being an increasingly important public health problem. Adipose tissue is no longer considered a passive bystander in body-weight regulation. It actively secretes a large number of hormones, growth factors, enzymes, cytokines, complement factors and matrix proteins, at the same time as expressing receptors for most of these elements, which influence fuel storage, mobilisation and utilisation at both central and peripheral sites. Thus, an extensive cross talk at a local and systemic level in response to specific external stimuli or metabolic changes underpins the multifunctional characteristics of adipose tissue. In addition to the already-known adipokines, such as IL, TNFalpha, leptin, resistin and adiponectin, more recently attention has been devoted to 'newcomers' to the 'adipose tissue arena', which include aquaporin, caveolin, visfatin, serum amyloid A and vascular endothelial growth factor. While in vitro and in vivo experiments have provided extremely valuable information, the advances in genomics, proteomics and metabolomics are offering a level of information not previously attainable to help unlock the molecular basis of obesity. The potential and power of combining pathophysiological observations with the wealth of information provided by the human genome, knock-out models, transgenesis, DNA microarrays, RNA silencing and other emerging technologies offer a new and unprecedented view of a complex disease, conferring novel insights into old questions by identifying new pieces to the unfinished jigsaw puzzle of obesity.