The value of current interventions for obesity.

Obesity greatly increases risk of cardiovascular disease, metabolic syndrome, and diabetes mellitus. Most obese patients are unable to sustain appreciable weight loss; the body has a natural tendency to return to its previous weight. Although bariatric surgery is effective, it is not without risk. Until better treatments for obesity are available, management remains focused on lifestyle changes, drug therapy, and treating the metabolic complications of obesity. The main cause of metabolic dysfunction in obesity is visceral fat. Fat deposition in and around organs, skeletal muscle, and other tissues is thought to occur when subcutaneous adipose tissue stores are full. Creation of additional adipose-tissue stores is prevented by the mature adipocytes, which inhibit the differentiation of preadipocytes in a negative feedback loop. This inhibition is mediated, in part, by the renin-angiotensin system. Indeed, angiotensin II blockade has been shown to promote adipogenesis in vitro. Clinical studies are currently underway to investigate whether the angiotensin-II-receptor blocker telmisartan can stimulate adipogenesis, with the aim of diverting intramuscular fat back into adipose tissue and thereby restoring insulin sensitivity. If this effect can be demonstrated in humans, this type of agent might become the treatment of choice for obese or overweight people at risk of type 2 diabetes.