title: Adrenergic regulation of lipolysis in fat cells from hyperthyroid and hypothyroid patients.
abstract: The influence of thyroid hormones on the adrenergic regulation of lipolysis was studied in isolated adipocytes removed from the gluteal region of hyper- and hypothyroid women and compared in adipocytes from euthyroid normal women. Noradrenaline significantly enhanced lipolysis in hyperthyroid patients, whereas noradrenaline inhibited lipolysis in hypothyroid patients compared to that in controls. Moreover, beta-adrenergic sensitivity and responsiveness were 10- and 2-fold increased, respectively, in hyperthyroid patients. In hypothyroid patients, beta-adrenoceptor responsiveness was reduced by 50%, whereas beta-adrenergic sensitivity remained unchanged compared with that in controls. Furthermore, the alpha 2-adrenergic and adenosine-induced antilipolytic effects were similar in all thyroid states. The lowered beta-adrenergic responsiveness seen in hypothyroidism could be mimicked by agents acting at the levels of phosphodiesterase (enprofylline), adenylate cyclase (forskolin) and protein kinase (dibutyryl cAMP). In hyperthyroidism, the increased beta-adrenergic sensitivity and responsiveness were not seen when lipolysis was stimulated at the adenylate cyclase, phosphodiesterase, or protein kinase levels. There was no change in the numbers of adipocyte beta- and alpha 2-adrenoceptors in hypothyroidism. However, the number of beta-adrenergic binding sites was doubled, whereas the fraction and affinities of isoprenaline high affinity sites remained unchanged in hyperthyroidism. Thus, the influence of thyroid hormone on catecholamine-stimulated lipolysis in man acts through different mechanisms when adipocytes are exposed to high or low levels of thyroid hormones. In hyperthyroidism, lipolysis adapts to increasing energy demands through an increase in the beta-adrenoceptor number and, thus, a more effective coupling of the adenylate-cyclase complex. In hypothyroidism, the low lipolytic effect of catecholamines seems to be mainly due to an impairment at the protein kinase level or to the hormone-sensitive lipase itself.
authors.affiliation: Department of Medicine, Huddinge University Hospital, Karolinska Institute, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Wahrenberg
authors.forename: A
authors.initials: A
authors.lastname: Wennlund
authors.forename: P
authors.initials: P
authors.lastname: Arner
mesh_terms: D017667:Adipocytes / Q000737:chemistry / Q000378:metabolism*; D000328:Adult; D002469:Cell Separation; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D006980:Hyperthyroidism / Q000378:metabolism* / Q000503:physiopathology; D007037:Hypothyroidism / Q000378:metabolism* / Q000503:physiopathology; D008066:Lipolysis / Q000502:physiology*; D008875:Middle Aged; D011943:Receptors, Adrenergic, beta / Q000032:analysis / Q000502:physiology*
chemical_list: D011943:Receptors, Adrenergic, beta