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M. LAFONTAN and R. AGID

Institut de Physiologie, ERA 412 CNRS, 2 rue F. Magendie, 31400 Toulouse, France

(Received 20 January 1978)

It has never been clearly shown that endogenous corticotrophin (ACTH) affects the release of storage fat. Desbals, Desbals & Agid (1970) observed significant mobilization of lipid within a few hours of ablation of the adrenal glands in the rabbit; this response was prevented by hypophysectomy and could be restored by administration of ACTH. A possible extra-adrenal action of endogenous ACTH on adipose tissue was postulated from these results, but the experimental conditions were very different from those found in normal animals. This study was undertaken to investigate the physiological role of ACTH in the mobilization of fat in the rabbit. The rabbit was selected because of the extreme sensitivity of its adipose tissue to the lipolytic action of ACTH and its very slight responsiveness towards the lipolytic action of catecholamines in vivo (Desbals

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M. LAFONTAN and R. AGID

The effect of minor stressful stimuli (saline infusions or venepunctures) on lipid mobilization (estimated by plasma free fatty acids (FFA) and glycerol levels) was studied in two strains of conscious rabbits of various ages. Infusions of 0·9% (w/v) NaCl solution induced a prompt increase of FFA levels in naturally obese rabbits while this effect was absent in younger lighter animals. Administration of propranolol (a β-adrenoceptor blocking drug) beforehand did not prevent lipid mobilization. Adipose tissue in vitro was completely unresponsive to the lipid mobilizing action of adrenaline. The initial output of ACTH induced by stressful stimuli was quickly followed by the increase in the plasma concentration of FFA. A highly significant correlation (r = 0·84 or 0·85; P< 0·01) existed between plasma ACTH and FFA levels 30 and 60 min after the start of stress. Dexamethasone completely prevented lipid mobilization while adipose tissue in vivo and in vitro responded strongly to ACTH. Consequently the lack of response of plasma FFA concentrations in corticosteroid-treated rabbits seemed to be linked to the failure of the pituitary gland to mobilize ACTH rather than to the unresponsiveness of adipose tissue to the pituitary hormone.

Our data indicate that in the rabbit, under conditions of stress, ACTH is of greater physiological importance than catecholamines in the control of lipolysis.