Alterations in adipocyte response to lipolytic hormones during cold acclimation.
The effects of cold exposure (7 days, 5 degrees C) and cold acclimation (21 days, 5 degrees C) on the regulation of lipolysis were investigated in adipocytes isolated from epididymal fat pads of rats. Catecholamines stimulated lipolysis in an affinity sequence typical of the beta 1-adrenoceptor subtype: one-half maximum velocity (1/2 Vmax) isoproterenol (35 nM) much greater than 1/2 Vmax norepinephrine (150 nM) approximately 1/2 Vmax epinephrine (200 nM). Cold exposure markedly decreased the sensitivity (1/2 Vmax) and the responsiveness (Vmax) of the adipocytes to the lipolytic action of catecholamines. Addition of adenosine deaminase to fat cells isolated from cold-exposed rats did not normalize the lipolytic activity, suggesting that extracellular adenosine was not responsible for the obtunded lipolysis. This effect of cold exposure was transient as the lipolytic response to catecholamines was normal in fully cold-acclimated animals. Remarkably, the responsiveness of adipocytes to the lipolytic action of glucagon (200 nM) and adrenocorticotropic hormone (ACTH, 1 microM) progressively increased during cold acclimation. Adipocyte lipolytic response to dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP) and theophylline was normal in cold-exposed rats, indicating that the lipolytic defect resides at an early step in the lipolytic cascade (pre-cAMP). On the other hand, the antilipolytic effect of insulin on norepinephrine-induced lipolysis significantly decreased during cold acclimation, particularly at physiological levels of insulin (nanomolar level). These results demonstrate that the transient decrease in the lipolytic action of catecholamines observed during cold acclimation is compensated by 1) an increased responsiveness of adipocytes to glucagon and ACTH and 2) by a decreased effectiveness of insulin to induce antilipolysis.(ABSTRACT TRUNCATED AT 250 WORDS)
Rochon
L
L
Department of Physiology, Faculty of Medicine, Laval University, Quebec, Canada.
Bukowiecki
L J
LJ
D000064:Acclimatization; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D003080:Cold Temperature; D004837:Epinephrine / Q000494:pharmacology*; D005934:Glucagon / Q000494:pharmacology*; D006358:Hot Temperature; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D000324:Adrenocorticotropic Hormone; D005934:Glucagon; D007545:Isoproterenol; D009638:Norepinephrine; D004837:Epinephrine