Adrenalectomy induced anorexia in gold thioglucose-treated obese mice: Metabolic and hormonal changes

Abstract

Adrenalectomy of gold thioglucose (GTG)-treated hyperphagic obese mice had been shown by us earlier to result in anorexia, weight loss, hypoglycemia and subsequent death of all mice. More recent studies suggest that adipose tissue mass may not be the critical determinant of anorexia since a large proportion of GTG-treated non obese (pair-fed to curb obesity) mice when challenged with adrenalectomy also developed anorexia. The aim of the present studies was to determine whether the changes in circulating metabolites, namely, glucose, free fatty acids and hormones, including insulin, glucagon and ACTH, which accompany adrenalectomy, might provide a clue to the causative agent for the onset of anorexia in GTG obese and non obese mice. Accordingly, plasma levels of glucose, free fatty acids, insulin, glucagon and ACTH were measured in GTG-treated obese, non obese and in normal untreated mice following adrenalectomy or a sham operation. Preoperatively, plasma insulin levels were significantly elevated in GTG obese mice whereas plasma glucose, free fatty acids and glucagon levels were not appreciably different than those of untreated controls. Upon adrenalectomy and onset of anorexia, GTG obese mice exhibited a progressive decline in blood glucose and insulin levels; plasma free fatty acids increased precipitously but only after the first day. Plasma glucagon levels declined immediately following adrenalectomy, however, by the 6th day postoperatively they were significantly elevated above the sham operated obese and untreated controls. Prior to adrenalectomy, the pair-fed GTG non obese mice exhibited blood glucose and insulin levels well below the levels of untreated controls and GTG obese mice whereas plasma free fatty acids and glucagon levels were markedly elevated. Upon adrenalectomy and a return to ad lib feeding, the GTG non obese mice which developed anorexia after a latent period of 2–3 days responded, like the GTG obese adrenalectomized mice, with a decline in blood glucose and insulin levels and an increase in plasma free fatty acids. Unlike the obese adrenalectomized anorexic mice, the non obese anorexic mice exhibited a marked elevation in plasma glucagon levels. Liver glycogen and abdominal adipose tissue reserves were significantly reduced in all anorexic mice at 10–15 days after adrenalectomy. The surviving GTG non obese adrenalectomized mice which exhibited normal feeding behavior had circulating metabolite and hormone levels that were indistinquishable from those of the sham operated untreated controls. There was no significant differences in blood corticosterone and ACTH levels among the sham operated groups. Blood corticosterone levels were less than 0.5 μg% and ACTH levels exceeded 200 ng% in all adrenalectomized mice. In conclusion, the rapid onset of anorexia and delayed elevation in plasma free fatty acids in GTG obese mice upon adrenalectomy indicates that the elevation of plasma free acids is the consequence of anorexia rather than the cause of it. Furthermore, the maintenance of food intake in surviving GTG non obese adrenalectomized mice in the presence of adrenal insufficiency suggests involvement of humoral factors, as yet unidentified, which affect a component of the regulatory mechanism for the control of food intake.