beta-Adrenergic control of stearoyl-CoA desaturase 1 repression in relation to sympathoadrenal regulation of thermogenesis.
Mice lacking beta-adrenoceptors, which mediate the thermogenic effects of norepinephrine and epinephrine, show diminished thermogenesis and high susceptibility to obesity, whereas mice lacking stearoyl-CoA desaturase 1 (SCD1), which catalyzes the synthesis of monounsaturated fatty acids, show enhanced thermogenesis and high resistance to obesity. In testing whether beta-adrenergic control of thermogenesis might be mediated via repression of the SCD1 gene, we found that in mice lacking beta-adrenoceptors, the gene expression of SCD1 is elevated in liver, skeletal muscle and white adipose tissue. In none of these tissues/organs, however, could a link be found between increased sympathetic nervous system activity and diminished SCD1 gene expression when thermogenesis is increased in response to diet or cold, nor is the SCD1 transcript repressed by the administration of epinephrine. Taken together, these studies suggest that the elevated SCD1 transcript in tissues of mice lacking beta-adrenoceptors is not a direct effect of blunted beta-adrenergic signalling, and that beta-adrenergic control of SCD1 repression is unlikely to be a primary effector mechanism in sympathoadrenal regulation of thermogenesis. Whether approaches that target both SCD1 and molecular effectors of thermogenesis under beta-adrenergic control might be more effective than targeting SCD1 alone are potential avenues for future research in obesity management.
Mainieri
D
D
Department of Medicine/Physiology, University of Fribourg, Fribourg, Switzerland.
Montani
J P
JP
Seydoux
J
J
Giacobino
J P
JP
Boss
O
O
Dulloo
A G
AG
D052436:Adipose Tissue, White / Q000201:enzymology; D000818:Animals; D004837:Epinephrine / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D008099:Liver / Q000201:enzymology; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013230:Stearoyl-CoA Desaturase / Q000096:biosynthesis* / Q000235:genetics; D013564:Sympathetic Nervous System / Q000502:physiology; D022722:Thermogenesis / Q000502:physiology*
D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase; D004837:Epinephrine