Changes in Lipolytic Activity of Isolated Adipocytes from Rats throughout Life Span

Abstract

The lipolytic response of isolated adipocytes from 1 ½-, 6-, 24- and 32-month-old rats to various doses of epinephrine was studied. Both the basal and the maximal stimulated glycerol release were largest in the mature rats (6 months old) which had the largest adipocytes. Expressing glycerol release per unit cell surface area (which was drastically reduced with age) eliminated the difference between mature and senescent rats both in absence of epinephrine and at high doses of the hormone. However, at low epinephrine doses the adipocytes of the very young and the very old rats showed an enhanced response per unit surface area. A simple pharmacodynamic analysis based on the occupancy theory of drug-receptor interaction suggests that the sensitivity of rat adipocyte receptors is increased during senescence; this increase may be related to the decreased surface of old adipocytes. On the other hand, the decreased maximal lipolytic response during senescence may be due in part to a reduced number of receptors and to a reduced sensitivity of the cellular enzymatic system underlying lipolysis.

The Aging Fat Cell

“…Moreover, on the basis of fat cell size, a number of conflicting results have been obtained. In some studies, higher rates of stimulated lipolysis were found in large adipocytes than in small ones, 104,229 whereas in other studies, no differences were detected between large and small adipocytes 254,255 . Fatcell size, as well as the mode of expression of the results, has to be carefully taken into account when attempting to analyze the lipolytic responses.…”

“…Even in laboratory rodents more suitable to this kind of analysis, data are scanty on the respective roles of hyperplasia and hypertrophy of adipocytes in changes in adipose tissue mass with aging. In the rat, a decline of fatness is noted in old age 92,93,101–104 . If a positive correlation between size of adipocytes and the weight of the body and of the adipose tissue does exist during the growth phase, this correlation is far less evident thereafter 87,93,104–109 .…”

“…In the rat, a decline of fatness is noted in old age 92,93,101–104 . If a positive correlation between size of adipocytes and the weight of the body and of the adipose tissue does exist during the growth phase, this correlation is far less evident thereafter 87,93,104–109 . In the majority of these studies, however, a decrease in adipocyte size is observed in senescent animals aged two years and older.…”

“…Among the lipolysis‐stimulating agents, the age‐related changes in sensitivity to catecholamines have received much attention. The level of circulating catecholamines is augmented with age, 256–258 but the lipolytic response of adipose tissue is reduced 104,108,109,259–262 . On the other hand, a negative correlation between adipocyte sensitivity to epinephrine and adipocyte volume has been described 104 .…”

“…The level of circulating catecholamines is augmented with age, 256–258 but the lipolytic response of adipose tissue is reduced 104,108,109,259–262 . On the other hand, a negative correlation between adipocyte sensitivity to epinephrine and adipocyte volume has been described 104 . As the evolution of fat‐cell size with age may be biphasic, presenting an increase in volume during maturation and a decrease in senescence, this may explain the rebound effect (decrease at maturity followed by increase at old age) in epinephrine‐sensitivity that has been noted in some studies 229 …”