Lipid mobilization and energy metabolism: impact of molecular and cellularapproaches on the treatment of obesity

There is strong evidence that reduced sympathetic nervous system (SNS) acti vity is involved in the etiology of obesity in several animal models of obe sity. In humans the situation is more complex but humans with low SNS activ ity, reduced beta-adrenergic sensitivity, reduced lipid mobilizing efficacy of catecholamines have lowered energy expenditure and are at greater risk of obesity. The SNS with its effect on food intake, lipid mobilization and energy expenditure has a major potential as a target for novel pharmacother apies in weight reducing strategies. Extended cellular and molecular knowle dge about the nature, the distribution and the role of the adrenergic recep tors (beta(1)-, beta(2), beta(3)-, alpha(2)- and alpha(1)-) existing in tis sue effecters involved in the control of lipid mobilization (adipose tissue ) and energy expenditure (brown adipose tissue, skeletal muscle) has opened new pathways for pharmacological strategies. In this manuscript, after a s ummary of current knowledge on the regulation of lipid mobilization and ene rgy expenditure in humans, we breifly review the putative targets and the m ost recent attempts to develop agents acting at various adrenergic receptor types in SNS effectors or on SNS activity. These include major questions a bout putative utilization of beta(3)-agonists, alpha(2)-antagonists and bet a-antagonists in pharmacotherapy and/or prevention of obesity in humans.