The Effect of Epinephrine on Fat Metabolism in Old Rats

Jelinková-Tenorová, M.; Hruza, Z

doi:10.1159/000211190

Cited by 105 publications

(7 citation statements)

References 3 publications

(3 reference statements)

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“…In studies of catecholamine-stimulated lipolysis, several groups have reported decreased lipolysis by catecholamines in aged rats both in vivo and in vitro (22)(23)(24). However, recent studies in the rat which considered age-related variation in triglyceride content with cell size noted little change in catecholamine stimulation of lipolysis when the data were expressed per cell rather than per milligram triglyceride (21,25,26).…”

Section: Discussionmentioning

confidence: 99%

Hormone-sensitive fat cell adenylate cyclase in the rat. Influences of growth, cell size, and aging.

Cooper¹,

Gregerman²

1976

J. Clin. Invest.

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A B S T R A C T The possibility has been explored that decreases of adenylate cyclase may explain diminished hormone sensitivity of adipose tissue with aging. Isolated cells were prepared from epididymal fat pads of rats 1-, 2-, 6-, 12-, and 24-mo-old, fixed in OsO, and sized and counted with a Coulter apparatus. Adenylate cyclase was assayed in cell membranes (ghosts) using [ra-P] 6 and 24 mo per cell. Glucagon stimulated adenylate cyclase 4.5-fold relative to basal in the 1-mo-old rat, but its effect then rapidly decreased and was absent by 12 mo. The fourfold stimulation by ACTH noted in the 1-mo-old animals decreased gradually with age but was still twice basal at 24 mo. Since no significant change of cell size occurred after 6 mo, diminished hormone sensitivity with senescence cannot be related to cell size. Similar age-related patterns of hormonal activation were evoked by 5'-guanylyl-imidodiphosphate [GMP-P(NH)P], a nucleotide analogue which increased both basal-and hormone-activated enzyme at all ages studied. Dose-response curves to hormones, fluoride, and GMP-P(NH)P were not affected by age. High Mg++ (50 mM) in the presence of GMP-P-(NH) P stimulated adenylate cyclase to levels greater than with fluoride, but a similar loss of activity with aging was still observed. Loss of hormone receptors may partially explain the age-related decreases of glucagon and ACTH-sensitive adenylate cyclase, but decreased basal-, epinephrine-, fluoride-, and GMP-P-(NH)P-stimulated responses suggest loss of the catalytic component of the adenylate cyclase enzyme complex in the aging fat cell membranes. INTRODUCTIONIn the past, most studies of aging and hormones have dealt with effects of hormones on the processes of aging or, more often, with effects of aging on hormone secretion and metabolism (1). More recently, however, effects of aging on hormone responsiveness or sensitivity have come under investigation. A number of postmaturational changes of this type have now been identified. In view of the variety of mechanisms involved in the actions of hormones of different types, it is not surprising that a mixed picture has emerged (2). For the many hormones whose mechanism of action involves activation of adenylate cyclase, relatively little information on age relationships is as yet available. To extend our information in this area, and with the hope of being able eventually to relate the findings to physiologic events, we have undertaken studies of adenylate cyclases in a variety of animal and human tissues.

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Section: Discussionmentioning

confidence: 99%

Hormone-sensitive fat cell adenylate cyclase in the rat. Influences of growth, cell size, and aging.

Cooper¹,

Gregerman²

1976

J. Clin. Invest.

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“…Though specifics are lacking, the results of some studies suggest that changes in drug activity with age are the result of impaired circulation and membrane permeability. For example, it has been proposed that impaired transport and distribution of epinephrine may account for the reduced epinephrine-induced alteration in blood nonesterified fatty acid levels seen in old animals (47). In this study, old animals exhibited a somewhat smaller increase than young animals in the circulating levels of nonesterified fatty acid after a given dose of epinephrine, whereas no changes in response were noted in vitro when adipose tissue from animals of different ages was incubated with epinephrine, indicating that less epinephrine reached its site of action.…”

Section: Drug Distributionmentioning

confidence: 99%

Pharmacodynamic Principles of Drug Therapy in the Aged*

Bender¹

1974

J American Geriatrics Society

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The geriatric patient responds differently to some drugs than does the younger adult, and consequently certain precautions should be taken when prescribing a therapeutic regimen for the elderly. Increasing age is accompanied by functional changes in many of the systems that control the way a drug is metabolized and the response that it evokes. Apparently it is these changes which underlie the modified effect seen clinically in geriatric patients. Age tends to reduce and delay the absorption of substances from the gastrointestinal tract, impair and delay drug clearance and excretion by the kidneys, and reduce the rate of enzyme destruction. The plasma half‐life of penicillin, digoxin, antipyrine, or phenylbutazone is extended significantly in the aged so that higher circulating concentrations are maintained for longer periods. Other age‐related changes influence the effect of a drug once it has combined with its receptor. These include an altered number of receptor sites, a decrease in the transmitter content of affected tissues, an increase in the rigidity of responsive tissues, and an overall decline in homeostatic capability.

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“…This implies that aging exerts an effect on adipocyte catecholamine sensitivity that is independent of cell size 60,61,96 . The ability of injected catecholamines to elicit increases in plasma free fatty acids declines with advancing age, while increases in plasma glucose are uniform 97,98 . Age‐related changes in the capacity of adipose tissue to release lipid upon stimulation by catecholamines therefore appear to be independent of the effects of catecholamines on other metabolic processes.…”

Section: Effects Of Catecholamines On Aging Adipocytesmentioning

confidence: 99%

“…Many reports of reduced glycerol release, reduced free fatty acid release, and reduced adenylate cyclase sensitivity to catecholamines with aging have appeared 24,45,60,61,63,68,74,84,95–102 . There are only a few reports of increased catecholamine‐stimulated lipolysis with age or weight 64,76,100 .…”

Section: Effects Of Catecholamines On Aging Adipocytesmentioning

confidence: 99%

Adipocyte Hormone Responsiveness and Aging in the Rat: Problems in the Interpretation of Aging Research

Kirkland

Dax

1984

J American Geriatrics Society

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Fat is a metabolically dynamic tissue. Its metabolism is under the control of several well-characterized hormonal systems. There appear to be changes in the hormonal sensitivity of rat fat with age. No single mechanism has been proved to explain all the changes observed in adipocyte hormonal responsiveness with aging, although it does seem likely that age does have an independent effect on fat metabolism from studies to date.

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The Effect of Epinephrine on Fat Metabolism in Old Rats

Cited by 105 publications

References 3 publications

Hormone-sensitive fat cell adenylate cyclase in the rat. Influences of growth, cell size, and aging.

Hormone-sensitive fat cell adenylate cyclase in the rat. Influences of growth, cell size, and aging.

Pharmacodynamic Principles of Drug Therapy in the Aged*

Adipocyte Hormone Responsiveness and Aging in the Rat: Problems in the Interpretation of Aging Research

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