Benidipine induces thermogenesis in brown adipose tissue by releasing endogenous noradrenaline: a possible mechanism for the anti-obesity effect of calcium antagonists

• DOI: 10.1038/sj.ijo.0800800
• Publication Date: 2002-09-04T17:15:24Z
• Authors: J Zhao; V Golozoubova; T Bengtsson; B Cannon; J Nedergaard
• Keywords: Male; 2. Zero hunger; Dihydropyridines; Adrenergic beta-Antagonists; Calcium Channel Blockers; Propranolol; Rats; 3. Good health; Rats, Sprague-Dawley; Mice; Norepinephrine; 03 medical and health sciences; 0302 clinical medicine; Adipose Tissue, Brown; Cricetinae; Animals; Obesity; Body Temperature Regulation

Anti-obesity effects of calcium antagonists such as benidipine and nifedipine have been described in rodent obesity models, but the mode of action of the calcium antagonists as anti-obesity agents has not been established.To examine whether the anti-obesity effects of calcium antagonists (here benidipine) could be ascribed to a direct stimulation of brown adipose tissue (BAT) thermogenesis.Examination of the ability of benidipine to induce thermogenesis (increased rate of oxygen consumption) in isolated brown-fat cells from rats, mice and hamsters--and in intact cold-acclimated rats.Benidipine itself, or in combination with any dose of noradrenaline (NA), was totally unable to induce or augment thermogenesis in isolated brown-fat cells of any species tested. However, it markedly induced thermogenesis in intact animals (approx 60% increase over resting metabolic rate). This effect could be fully inhibited by propranolol.Benidipine is itself without thermogenic effect. The thermogenic response in-vivo (and thus presumably the anti-obesity effect) is probably secondary to a previously described general side-effect of calcium antagonists: a release of NA from sympathetic nerves, here most likely directly from nerves in the BAT. The anti-obesity effect of benedipine is thus probably not due to its calcium channel blocking effect.It is probable that the anti-obesity effects of calcium antagonists reported in several models of genetically obese rodents (MSG-obese and agouti mice, SHHF/Mcc-fa(cp) and JCR:LA-corpulent rats) are mediated via an indirect stimulation of BAT. To what extent calcium antagonists may induce similar effects in a clinical situation, is currently unknown.