[Lipid mobilization and energy metabolism: impact of molecular and cellular approaches on the treatment of obesity].
There is strong evidence that reduced sympathetic nervous system (SNS) activity is involved in the etiology of obesity in several animal models of obesity. In humans the situation is more complex but humans with low SNS activity, 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 pharmacotherapies in weight reducing strategies. Extended cellular and molecular knowledge about the nature, the distribution and the role of the adrenergic receptors (beta(1)-, beta(2)-, beta(3)-, alpha(2)- and alpha(1)-) existing in tissue effectors 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 summary of current knowledge on the regulation of lipid mobilization and energy expenditure in humans, we briefly review the putative targets and the most recent attempts to develop agents acting at various adrenergic receptor types in SNS effectors or on SNS activity. These include major questions about putative utilization of beta(3)-agonists, alpha(2)-antagonists and beta-antagonists in pharmacotherapy and/or prevention of obesity in humans.
Lafontan
M
M
Unité INSERM 317, Université Paul Sabatier, Institut Louis Bugnard, CHU Rangueil, 31403 Toulouse cedex 4. lafontan@rangueil.inserm.fr
Berlan
M
M
Galitzky
J
J
D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000502:physiology; D058671:Adrenergic beta-1 Receptor Antagonists; D058672:Adrenergic beta-2 Receptor Antagonists; D058673:Adrenergic beta-3 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D001833:Body Temperature Regulation; D004700:Endocrine System Diseases / Q000150:complications / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D015444:Exercise / Q000502:physiology; D006801:Humans; D050356:Lipid Metabolism; D008066:Lipolysis / Q000502:physiology*; D009765:Obesity / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics / Q000502:physiology; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*
D058671:Adrenergic beta-1 Receptor Antagonists; D058672:Adrenergic beta-2 Receptor Antagonists; D058673:Adrenergic beta-3 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2