Some Effects of Adrenalectomy in the Fatty Rat*

Yukimura, Yaichiro; Ga, Bray; Ar, Wolfsen

doi:10.1210/endo-103-5-1924

Cited by 120 publications

(44 citation statements)

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“…On the other hand, bilateral adrenalectomy (ADX) reduces food intake and body weight gain, and these effects are reversed by glucocorticoid replacement in rats (12). Furthermore, ADX reduces hyperphagia and obesity in different experimental models, whereas glucocorticoid replacement reverses these effects (4,8,52). Hypophagia induced by ADX has been associated with a decrease of mRNA expression of hypothalamic neuropeptide Y (NPY), a potent orexigenic neuropeptide (41).…”

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confidence: 99%

Hypophagia induced by glucocorticoid deficiency is associated with an increased activation of satiety-related responses

Uchôa¹,

Sabino²,

Ruginsk³

et al. 2009

Journal of Applied Physiology

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Uchoa ET, Sabino HA, Ruginsk SG, Antunes-Rodrigues J, Elias LL. Hypophagia induced by glucocorticoid deficiency is associated with an increased activation of satiety-related responses. J Appl Physiol 106: 596 -604, 2009. First published November 20, 2008 doi:10.1152/japplphysiol.90865.2008.-Glucocorticoids have major effects on food intake, demonstrated by the decrease of food intake following adrenalectomy. Satiety signals are relayed to the nucleus of the solitary tract (NTS), which has reciprocal projections with the arcuate nucleus (ARC) and paraventricular nucleus (PVN) of the hypothalamus. We evaluated the effects of glucocorticoids on the activation of hypothalamic and NTS neurons induced by food intake in rats subjected to adrenalectomy (ADX) or sham surgery 7 days before the experiments. One-half of ADX animals received corticosterone (ADXϩB) in the drinking water (B: 25 mg/l). Fos/tyrosine hydroxylase (TH), Fos/corticotrophin-releasing factor (CRF) and Fos immunoreactivity were assessed in the NTS, PVN, and ARC, respectively. Food intake and body weight were reduced in the ADX group compared with sham and ADXϩB groups. Fos and Fos/TH in the NTS, Fos, and Fos/CRF immunoreactive neurons in the PVN and Fos in the ARC were increased after refeeding, with higher number in the ADX group, compared with sham and ADXϩB groups. CCK administration showed no hypophagic effect on ADX group despite a similar increase of Fos/TH immunoreactive neurons in the NTS compared with sham and ADXϩB groups, suggesting that CCK alone cannot further increase the anorexigenic effect induced by glucocorticoid deficiency. The present data indicate that glucocorticoid withdrawal reduced food intake, which was associated with higher activation of ARC, CRF neurons of the PVN, and catecholaminergic neurons of the NTS. In the absence of glucocorticoids, satiety signals elicited during a meal lead to an augmented activation of brain stem and hypothalamic pathways. glucocorticoids; food intake; satiety signals; nucleus of the solitary tract; paraventricular nucleus of the hypothalamus; arcuate nucleus of the hypothalamus GLUCOCORTICOIDS PLAY AN IMPORTANT ROLE in the control of feeding behavior. Increased food intake and body weight gain are associated with glucocorticoid treatment in humans (46). On the other hand, bilateral adrenalectomy (ADX) reduces food intake and body weight gain, and these effects are reversed by glucocorticoid replacement in rats (12). Furthermore, ADX reduces hyperphagia and obesity in different experimental models, whereas glucocorticoid replacement reverses these effects (4,8,52). Hypophagia induced by ADX has been associated with a decrease of mRNA expression of hypothalamic neuropeptide Y (NPY), a potent orexigenic neuropeptide (41). ADX also may reduce food intake through the increase of corticotrophin-releasing factor (CRF) mRNA expression in the paraventricular nucleus (PVN), since CRF is a well-known anorexigenic peptide (1, 2). CRF neurons in the PVN receive projections from neurons of the nucleus of the...

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confidence: 99%

Hypophagia induced by glucocorticoid deficiency is associated with an increased activation of satiety-related responses

Uchôa¹,

Sabino²,

Ruginsk³

et al. 2009

Journal of Applied Physiology

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“…Adrenalectomy (ADX), when performed before weaning, prevents development of all hormonal, metabolic and behavioural abnormalities including hyperinsulinaemia in fa/fa rats [19,20] and these same abnormalities are partially reduced when ADX is carried out in adult rats [21,22]. The effects of ADX are reversed by glucocorticoid replacement [20,22].…”

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“…The effects of ADX are reversed by glucocorticoid replacement [20,22]. The mechanism by which ADX normalizes or reduces insulin secretion is still not clear; however, reduced food intake [21,23], or removal of the inhibitory effect of corticosterone on the autonomic nervous system activity to the endocrine pancreas [20] may both play crucial roles. We considered that ADX might prevent hyperinsulinaemia by altering glucose metabolism within the beta cells and decided to study glucokinase function because of its glucose sensing role and known abnormalities in fa/fa rats.…”

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Effect of adrenalectomy on the development of a pancreatic islet lesion in fa/fa rats

Kibenge

Chan

1996

Diabetologia

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Summary Adrenalectomy prevents development of obesity and hyperinsulinaemia in obese (fa/fa)Zucker rats, thereby implicating the hypothalamopituitary-adrenal axis in the pathogenesis of obesity. In this study glucose-induced insulin secretion and glucokinase activity were investigated in isolated islets from adrenalectomized and control obese and lean female rats. Islets from control fa/fa rats were more sensitive to glucose with a half-maximal effective concentration (ECs0) of 6.1 + 2.0 mmol. 1-1 compared with 10.6 + 2.7 mmol. 1-1 for adrenalectomized fa/fa rat islets. Adrenalectomy did not alter the islet sensitivity to glucose in the lean rats (ECs0 of 9.4+1.5mmo1.1-1 and 9.3+2.0mmo1-1-1 for adrenalectomized and control lean rats respectively). Mannoheptulose did not inhibit insulin secretion from control obese rats; however at concentrations of 1.0 mmol 9 1-1 or more it significantly inhibited glucose-induced insulin secretion in adrenalectomized obese and lean, and control lean rat islets (p < 0.05).In adrenalectomized fa/fa islets the glucokinase K m was increased twofold compared with the control fa/fa rats (9.5 + 1.5 mmol. 1-1 vs 5.0 + 1.5 mmol. 1-1, respectively), but there was no significant change in glucokinase K m in the lean rat islets after adrenalectomy. Mannoheptulose (10 mmol. 1-1) caused a significant reduction in glucose phosphorylation in disrupted islets of adrenalectomized fa/fa and lean, and of control lean rats, but not of control fa/fa rats. These data demonstrate that development of abnormal regulation of glycolysis in pancreatic islet beta cells offa/ fa rats, as indicated by the insulin response to mannoheptulose and glucokinase activity, is dependent on an intact hypothalamo-pituitary-adrenal axis. [Diabetologia (1996) 39: 190-198] Key words Insulin secretion, mannoheptulose, adrenalectomy, glucokinase, hypothalamo-pituitary-adrenal axis, islets of Langerhans.Hyperinsulinaemia is a characteristic of human obesity and the genetically transmitted obesity syndromes Abbreviations: ADX, Adrenalectomy/adrenalectomized; CRH, corticotrophin releasing hormone; DMEM, Dulbecco's modified Eagle's medium; ECs0; half-maximal effective concentration; HPA, hypothalamo-pituitary-adrenal; MH, mannoheptulose; Hepes, 4-(2-hydroxyethyl)-l-piperazineethane sulphonic acid.high-carbohydrate diet plays a significant role in the development of obesity and hyperinsulinaemia in these rats [2]. Increased sensitivity to glucose of the pancreatic beta cells of fa/fa rats in both the preobese [3][4][5] and adult stages [6][7][8][9] is observed. This increased response offa/fa rats to glucose stimulation might be related to changes in the primary glucose sensing mechanisms of the pancreatic islet beta cells because sensitivity to other stimulants is not different from that observed in lean rats [9].Glucokinase, for which there is growing evidence as the primary pancreatic beta-cell glucose sensor [10], is reported to have increased sensitivity to glucose in fa/fa rat isolated islets [11]. The activity of glucoki...

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“…Although the ability of ADX to lower circulating glucose levels has been confirmed in several animal models of obesity, including the GTG-obese mouse (1,3,9,18,21,23), the mechanism(s) by which ADX lowers glucose levels remains unclear. Hypophagia has been postulated as a cause of lower plasma glucose levels after ADX (9), but in some studies ADX of GTGinjected mice had only a small effect on food intake and no effect on food intake of control mice (1).…”

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confidence: 99%

Hepatic Gluconeogenesis and the Activity of PDH in Individual Tissues of GTG‐Obese Mice Following Adrenalectomy

et al. 1996

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1996;4:367-375. Adrenalectomy (ADX) lowers circulating glucose levels in animal models of non-insulin dependent diabetes (NIDDM) and obesity. To investigate the role of hepatic glucose production (HGP) and tissue glucose oxidation in the improvement in glucose tolerance, hepatocyte gluconeogenesis and the activity of pyruvate dehydrogenase (pDH) were examined in different tissues of gold thioglucose (GTG) obese mice 2 weeks after ADX or sham ADX. GTG-obese mice which had undergone ADX weighed significantly less than their adrenal intact counterparts (GTG ADX: .37.5 ± 0.7g; GTG: 44.1 ± 0.4g; p<0.05), and demonstrated lower serum glucose (GTG ADX: 22.5 ± 1.6 mmollL; GTG: 29.4 ± 1.9 mmollL; p<0.05) and serum insulin levels (GTG ADX: 76 ± 10JlU/mL; GTG: 470 ± 63JlU/mL; p<0.05). Lactate conversion to glucose by hepatocytes isolated from ADX GTG mice was significantly reduced compared with that of hepatocytes from GTG mice (GTG ADX: 125 ± 10 nmol glucosell0 6 cells; GTG: 403 ± 65 nmol glucosell0 6 cells; p<0.05). ADX also significantly JlIDol/liver; GTG: 614 ± 60 umol/llver; p<0.05) and fatty acid content (GTG ADX: 101 ± 9 mg fatty acidlg liver; GTG: 404 ± 40 mg fatty acidlg liver; p<0.05) of the liver of GTG-obese mice. ADX of GTG-obese mice reduced PDH activity by varying degrees in all tissues, except quadriceps muscle. These observations are consistent with an ADX induced decrease in hepatic lipid stores removing fatty acid-induced increases in gluconeogenesis and increased peripheral availability of fatty acids inhibiting PDH activity via the glucose/fatty acid cycle. It is also evident that the improvement in glucose tolerance which accompanies ADX of GTGobese mice is not due to increased PDH activity resulting in enhanced peripheral glucose oxidation. Instead, it is more likely that reduced blood glucose levels after ADX of GTG-obese mice are the result of decreased gluconeogenesis in the liver.

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Some Effects of Adrenalectomy in the Fatty Rat*

Cited by 120 publications

References 9 publications

Hypophagia induced by glucocorticoid deficiency is associated with an increased activation of satiety-related responses

Hypophagia induced by glucocorticoid deficiency is associated with an increased activation of satiety-related responses

Effect of adrenalectomy on the development of a pancreatic islet lesion in fa/fa rats

Hepatic Gluconeogenesis and the Activity of PDH in Individual Tissues of GTG‐Obese Mice Following Adrenalectomy

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