Alpha-adrenergic responses in rabbit white fat cells: the influence of obesity and food restriction.

The present work was carried out to separate the influence of age from that of fat cell size in rabbit white fat cells, in order to assess the importance of changing cell size to the age-related decrease of epinephrine responsiveness. Epinephrine action and adrenergic receptor site activities were explored in two main groups of rabbits. One group, 5-6 months of age, was divided into three subgroups: the control, group I, was fed usual laboratory chow; group II was subjected to dietary restriction (3 months); group III was fed the usual diet with chronic administration of insulin (1.5 UI/kg per day for 3 months) known to induce fat cell size increment. The other main group, composed of 15- to 16-month-old rabbits, was also divided into three subgroups: group IV, control; group V, subjected to dietary restriction (1 and one-half-2 months) after previous development of adipose mass; and group VI, dietrestricted for 4 months. The loss of epinephrine-responsiveness of rabbit fat cells can be either prevented by restricting food intake (groups III, V) or promoted by chronic insulin administration (group II). Isoproterenolinduced lipolysis was maintained whatever the fat-cell size, while the changes in the ability of epinephrine to promote lipolysis were linked to a variable alpha-adrenergic activity (increase of epinephrine-induced lipolysis promoted by the alpha-antagonist drug, phentolamine). Alpha-adrenergic responsiveness is increased in large fat cells (groups III and IV) while a reduced alpha-adrenergic activity is observed in small fat cells of underfed rabbits (group II). After dietary restriction, large fat cells (with an increased alpha-adrenergic responsiveness) were reduced in size and a significant restoration of the lipolytic effect of epinephrine was shown (group V). In conclusion, these results indicate that cell size, in addition to age, is an important factor affecting epinephrine-responsiveness in rabbit adipocytes. The loss or the recovery of the lipolytic effect of epinephrine could be explained by a modification of the alpha-receptor activity; the beta-receptor activity was less modified.