Obesity: molecular bases of a multifactorial problem

Obesity could well become the most common health problem of the 21st centur y. There are more opportunities to consume large quantities of food: big po rtions of tasty, varied food, at reasonable prices, are available everywher e. Moreover, our bodies are better adapted to combat weight loss than to co mbat weight gain, since for thousands of years our species evolved in circu mstances where nutrients were in short supply. The response of each individual to diet and other environmental factors var ies considerably, depending on the characteristics of his/her body weight c ontrol mechanisms. The differentiating element in the future, especially as regards the dietary and pharmacological control of obesity, will be knowle dge of an individual's possible response depending on his/her genetic backg round. Obesity can occur as a result of genetic or acquired changes in three main types of biochemical processes, which are the main focus of this review: a) feeding control, which determines the sensations of satiety and hunger thr ough processes that depend on an interplay between internal signals (notabl y leptin) and environmental factors; b) energy efficiency, in particular th e activation of thermogenesis mediated by uncoupling proteins (UCPs) that m akes it possible to dissipate part of the energy contained in food as heat instead of accumulating it as fat, and c) adipogenesis, the process by whic h cells specialised in fat storage (adipocytes) are formed, which is contro lled by an interplay of transcription factors, including members of the C/E BP, PPAR gamma and ADD families. The knowledge of a growing number of genes and molecules implicated in thes e three types of processes and of their metabolic relationships is leading toward a molecular understanding of the body weight regulatory system, and is paving the way for new methods of obesity control, especially pharmacolo gical but also nutritional and possibly involving genetic intervention.