Catecholamine-induced lipolysis in adipose tissue of the elderly.
Age-dependent alterations in the effects of catecholamines on lipolysis were investigated in 25 young (21-35 yr) and 10 elderly (58-72 yr) healthy, nonobese subjects using isolated adipocytes obtained from abdominal subcutaneous tissue. Basal lipolysis was not affected by aging, while the rate of catecholamine-stimulated lipolysis was reduced by 50% in the elderly subjects (P less than 0.005). To elucidate the mechanisms behind this phenomenon lipolysis was stimulated with agents that act at well-defined steps in the lipolytic cascade, from the receptor down to the final step: the activation of the protein kinase/hormone-sensitive lipase complex. All agents stimulated lipolysis at a 50% lower rate in elderly as compared with young subjects (P less than 0.05 or less). However, half-maximum effective concentrations of the lipolytic agents were similar in both groups. The antilipolytic effects of alpha 2-adrenoceptor agonists were also the same in young and old subjects. Moreover, the stoichiometric properties of the beta- and alpha 2-receptors did not change with increasing age. In vivo studies performed on the same individuals likewise demonstrated an impaired lipolytic responsiveness, with 50% lower plasma glycerol concentrations during exercise in the elderly subjects (P less than 0.05), in spite of a normal rise in plasma norepinephrine. The plasma glycerol levels correlated strongly to the glycerol release caused by catecholamine-stimulated lipolysis in vitro in both young and elderly subjects (r = 0.8-0.9, P less than 0.001). In conclusion, a decreased activation of the hormone-sensitive lipase complex appears to be the mechanism underlying a blunted lipolytic response of fat cells to catecholamine stimulation in elderly subjects. This finding may, explain the age-dependent decreased lipolytic response to exercise in vivo.
Lönnqvist
F
F
Department of Medicine, University Hospital, Huddinge, Sweden.
Nyberg
B
B
Wahrenberg
H
H
Arner
P
P
D000273:Adipose Tissue / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging; D002478:Cells, Cultured; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000494:pharmacology*; D011869:Radioligand Assay; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D015016:Yohimbine / Q000494:pharmacology
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D015016:Yohimbine; D007545:Isoproterenol; D009638:Norepinephrine