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

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A B S T R A C T Age-related decreases of hormonesensitive adenylate cyclase activities of rat fat cell plasma membranes (ghosts) have been recently described. Glucagon-sensitive activity was completely lost between 1 and 6 mo, an interval in which fat cell size increases rapidly, while decreased activation by ACTH was gradual over the entire life span of the animal (24 mo), and epinephrine-sensitive enzyme diminished modestly and only during senescence. In the present studies an attempt was made by restricting food intake to assess the importance of changing cell size in the age-related alterations of hormonesensitive enzyme activities. Enzyme activities were determined before restriction and at monthly intervals for 3 mo for the unstimulated enzyme (basal) though declining, were still 1.5-3 times greater than the unrestricted controls, regardless of whether activity was expressed as total activity per milligram ghost protein or per cell, or as fold-increase. In the young animals, basal and fluoride-sensitive activities after a 3-mo restriction were unchanged or had decreased only slightly, depending on the base line used. Dietary restriction of adult animals for 3 mo, in contrast to the results in the young, did not increase total hormone-stimulated activity but rather produced either 0% (per milligram protein) or 25% decrease (per cell) for epinephrine-sensitive enzyme, 25 or 50% decrease of ACTH response, and 40 or 60% decreases of basal-and fluoride-stimulated activities. Expression of activities of restricted adults as fold-increase (stimulate/basal) showed an "increase of responsiveness" for all three hormones, but this was a reflection of the marked decrease of basal activity. Nonetheless, the restricted adults showed significant restoration of a small amount of glucagon-sensitive activity (1.8-fold over basal). These results indicate that cell size, per se, is not a dominant factor affecting hormoneresponsive adenylate cyclase under conditions of dietary restriction. The data do not support the postulation that increasing cell size is directly related to the enzyme's decreased activity during aging. Hormonesensitive adenylate cyclase is, however, clearly under dietary control, while age determines the pattern of the observed response during dietary restriction.

Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 96%

See 1 more Smart Citation

Enhanced activity of hormone-sensitive adenylate cyclase during dietary restriction in the rat: dependence on age and relation to cell size.

Cooper¹,

Weinblatt²,

Gregerman³

1977

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“…In the rat, the impairment has been thought to be caused by an increased phosphodiesterase activity (13,29,30) or a more pronounced antilipolytic effect of adenosine (31,32). Nevertheless, a postreceptor defect has also been proposed (33).…”

Section: Discussionmentioning

confidence: 99%

Catecholamine-induced lipolysis in adipose tissue of the elderly.

Lönnqvist¹,

Nyberg²,

Wahrenberg³

et al. 1990

128

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 < 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 < 0.05 or less). However, half-maximum effective concentrations of the lipolytic agents were similar in both groups. The antilipolytic effects of alpha2-adrenoceptor agonists were also the same in young and old subjects. Moreover, the stoichiometric properties of the beta-and alpha2-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 < 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 < 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. (J.

“…A decreased lipolytic response to beta adrenergic stimulation has been demonstrated in vitro in older rats (5)(6)(7)(8)(9). Although the mechanism responsible for this change is not clear, studies with fat cell membranes (10) and isolated adipocytes (1 1) suggest that a reduction in adenylate cyclase activity is involved.…”

Section: Introductionmentioning

confidence: 99%

Palmitate and glycerol kinetics during brief starvation in normal weight young adult and elderly subjects.

Klein¹,

Young²,

Blackburn³

et al. 1986

120