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Endocrinology Vol. 140, No. 7 3183-3187
Copyright © 1999 by The Endocrine Society

ARTICLES

Selective Dependence of Intracerebroventricular Neuropeptide Y-Elicited Effects on Central Glucocorticoids1

Katerina E. Zakrzewska, Amanda Sainsbury, Isabelle Cusin, Juha Rouru, Bernard Jeanrenaud and Françoise Rohner-Jeanrenaud

Laboratoires de Recherches Métaboliques (K.E.Z., I.C., B.J., F.R.-J.), Geneva University, School of Medicine, The Garvan Institute of Medical Research (A.S.), Diabetes Research Group, Sydney, New South Wales 2010, Australia; Department of Pharmacology and Clinical Pharmacology (J.R.), University of Turku, 20014 Turku, Finland

Address all correspondence and requests for reprints to: Katerina E. Zakrzewska or Isabelle Cusin, Laboratoires de Recherches Métaboliques, Hôpital cantonal universitaire de Genève, 24, rue Micheli-du-Crest, 1211 Geneva 14, Switzerland. E-mail: katerina_z{at}hotmail.com


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
It has been reported that hyperphagia and excessive body weight gain of genetically obese rodents were abolished by adrenalectomy. High hypothalamic levels of neuropeptide Y (NPY) were found in obese rodents. A chronic intracerebroventricular (icv) infusion of NPY in normal rats was shown to produce most hormono-metabolic abnormalities of genetically obese animals, and to be inefficient in doing so in adrenalectomized (ADX) rats. The combined presence of NPY and of glucocorticoids thus appeared to be necessary for inducing obesity. This study, therefore, was aimed at determining the consequences of a chronic icv NPY infusion in ADX rats receiving or not icv glucocorticoids. It was found that the combined icv infusion of NPY and dexamethasone in ADX rats increased food intake, body weight, plasma insulin, leptin, and triglyceride levels relative to vehicle-infused ADX controls. The infusion of NPY alone, or of dexamethasone alone in ADX rats failed to produce these effects. In contrast, the icv infusion of NPY alone greatly decreased the expression of brown adipose tissue uncoupling protein-1 and -3. This was not modified by the superimposed infusion of dexamethasone. It is concluded that, although many of centrally elicited NPY effects require the central presence of glucocorticoids, those bearing on the inhibition of uncoupling proteins expression (energy dissipation) do not require central glucocorticoids.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
IT HAS BEEN previously shown that glucocorticoids were necessary for hyperphagia and excessive body weight gain of obese rodents to occur, as these processes completely disappeared when obese rodents were adrenalectomized (1, 2, 3, 4, 5).

Other experiments gave additional clues as to the possible etiology of genetic obesity syndromes in rodents, namely that most obese animals had elevated hypothalamic neuropeptide Y (NPY) levels (6, 7, 8, 9, 10). To substantiate the pathological role of increased central NPY levels in bringing about obesity, experiments of chronic intracerebroventricular (icv) infusion of NPY were carried out in normal rats. It was observed that rats icv infused with NPY developed, compared with vehicle-infused controls, marked hyperphagia, increased body weight gain, hyperinsulinemia, increased fat deposition, hypercorticosteronemia, and insulin resistance, all abnormalities also found in animal models of spontaneous obesity (11, 12, 13). The observation that other neuropeptides (e.g. galanin, melanin-concentrating hormone, and orexins) could be implicated in the occurrence of hyperphagia (14, 15, 16, 17), that leptin, a satiety factor, failed to exert its effect of decreasing food intake when its hypothalamic receptors were dysfunctional (18, 19, 20, 21), also supported the view of the importance of hypothalamic alterations in the etiology of animal obesity. Of final interest was the observation that the icv NPY-elicited effects mentioned above required glucocorticoids and did not occur when NPY was icv infused in adrenalectomized (ADX) rats (22). This suggested that the combined presence of NPY and glucocorticoids was necessary for an evolution toward obesity with its hormonal and metabolic alterations. Further, it appeared that the action of glucocorticoids on NPY effects could be mediated by the central nervous system (CNS). Indeed, it has been shown that glucocorticoid receptors are found on NPY-containing neurons in the hypothalamus (23), and that chronic administration of glucocorticoids increases prepro-neuropeptide Y messenger RNA in the arcuate nucleus (ARC) of adrenalectomized rats (24). Finally, the observation that NPY-induced feeding in rats is decreased by implants of RU486, a selective type II glucocorticoid receptor antagonist (25, 26), further suggested that it is the action of glucocorticoids within the CNS that is necessary to the obesity-like effects of chronic icv NPY infusion.

The aim of the present study was therefore to determine the consequences of a central (icv) NPY infusion in adrenalectomized rats receiving a superimposed central infusion of glucocorticoids.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Animals
Bilaterally adrenalectomized (ADX) female Sprague Dawley rats (body weight 225 ± 3 g, n = 4–7 in each group) were purchased from IFFA CREDO (L’Arbresle, France) and housed individually under conditions of controlled temperature and illumination (0700–1900 h). They were fed ad libitum a standard laboratory chow (Provimi-Lacta, Cossonay, Switzerland) and had free access to tap water supplemented with 9 g/liter NaCl.

icv infusion
At 12 weeks of age, all animals were equipped with a cannula placed in the right lateral cerebral ventricle (13). Adequate placement of the cannulae was tested with the drinking response to an icv injection of angiotensin (25 ng in 5 µl PBS, Novabiochem, Laüfelfingen, Switzerland) (27). Plasma corticosterone levels of adrenalectomized rats were below the limit of detection of the RIA (28). After a recovery period of 1 week, the infusions started. Four experimental groups were constituted. The first group was icv infused with the vehicle only (ADX + icv vehicle). The second group was icv infused with dexamethasone only (ADX + icv dex). The third group was icv infused with neuropeptide Y alone (ADX + icv NPY). The fourth group was icv infused with both neuropeptide Y and dexamethasone (ADX + icv NPY and dex). The infusions lasted for 5 days, and were carried out by sc implanted osmotic minipumps (model 2001, Alza Corp., Palo Alto, CA). The vehicle was a PBS, 0.04 M, pH 7.4, with 0.2% BSA and 0.01% ascorbic acid. Porcine NPY (Bachem, Bubendorf, Switzerland) and/or the synthetic glucocorticoid, dexamethasone, were infused at a dose of 15 µg/day and 1.8 µg/day, respectively. Dexamethasone was used due to the inability of corticosterone to be included in minipumps and, more importantly, because it binds with a higher affinity than corticosterone to type II glucocorticoid receptors known to be implicated in ingestive behavior (26, 29). Daily body weight and food intake were measured during the whole experimental period.

Plasma hormone and substrate measurements
Blood samples were collected from the tip of the tail at 0900 h on day 0 of the experiment, and at the end of the infusions from trunk blood taken when rats were killed by decapitation. Plasma samples were stored at -20 C until further measurements. Samples of day 0 were used to quantify corticosterone concentrations (28) to control the state of adrenalectomy. Insulin (30), leptin (kit from Linco Research, Inc.; St. Louis, MO), and triglyceride (kit from bioMérieux, Marcy-l’Etoile, France) concentrations were measured at the end of the experimental period.

Northern blot analysis
Total RNA was extracted from brown adipose tissue removed at the end of the experiment. Northern blot analysis of uncoupling protein-1 (UCP1), uncoupling protein-2 (UCP2), and uncoupling protein-3 (UCP3) was carried out as previously described, using probes defined elsewhere (31). Ratios of respective UCP/ß actin messenger RNA levels are expressed as a percentage of control values.

Statistical analysis
Food intake and body weight were analyzed by two-way ANOVA with repeated measurements. When a significant effect (P < 0.05) of dexamethasone, NPY, or the interaction was found, posthoc tests (Tukey’s procedure) were done to locate the difference in the groups. For the remaining data differences between groups were assessed by two-way ANOVA. When the dexamethasone and NPY effects, or the interaction effect, were found to be significant (P < 0.05), Fisher’s posthoc tests were performed to locate significant differences.


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
For food intake, a significant effect of dexamethasone (P = 0.00018) and dexamethasone x time interaction (P = 0.00011) was found (Fig. 1Go). Food intake of ADX rats icv infused only with NPY was not altered during the experimental period. However, icv NPY tended (ns) to increase food intake when dexamethasone was also infused. Two-way ANOVA followed by posthoc tests showed a significant effect of dexamethasone on body weight gain in ADX rats icv infused concomitantly with NPY (Fig. 2Go). The combined icv infusion of NPY and dexamethasone in the ADX group was accompanied by a marked increase in plasma insulin levels relative to all the other groups whose plasma insulin levels remained similar to those of icv vehicle-infused ADX control rats (Fig. 3Go). A similar observation was made for plasma leptin levels: the ADX rats icv infused with NPY and dexamethasone had a leptinemia of 17.2 ± 1.8 ng/ml, a value that was more than ten times higher than that of the three other groups, namely the icv vehicle-, icv NPY-, or icv dexamethasone-infused ones (Fig. 4Go). In addition, although no significant difference in plasma triglyceride levels was found between icv vehicle-, icv NPY-, or icv dexamethasone-infused ADX rats, such was not the case in the icv NPY- and dexamethasone-infused ADX group, in which the plasma triglyceride concentrations were significantly increased (Fig. 5Go).



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  		Figure 1. Daily food intake in adrenalectomized (ADX) rats during icv infusion of vehicle, dexamethasone alone (dex), NPY alone, and NPY plus dexamethasone (NPY and dex). Plotted data are means ± SEM of four to seven rats per group. Data were analyzed by two-way ANOVA for repeated measurements; dex effect (P = 0.00018) and dex x time interaction (P = 0.00018) were significant.

 


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  		Figure 2. Changes in body weight gain in adrenalectomized (ADX) rats during icv infusion of vehicle, dexamethasone alone (dex), NPY alone, and NPY plus dexamethasone (NPY and dex). Plotted data are means ± SEM of four to seven rats per group. Data were analyzed by two-way ANOVA, for repeated measurements, followed by a posthoc test. *, P < 0.05 vs. vehicle-infused controls.

 


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  		Figure 3. Plasma insulin levels in adrenalectomized (ADX) rats at the end of icv infusion of vehicle, dexamethasone alone (dex), NPY alone, and NPY plus dexamethasone (NPY and dex). Plotted data are means ± SEM of four to seven rats per group. Data were analyzed by two-way ANOVA followed by a posthoc test. *, P < 0.05 vs. vehicle-infused controls.

 


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  		Figure 4. Plasma leptin levels in adrenalectomized (ADX) rats at the end of icv infusion of vehicle, dexamethasone alone (dex), NPY alone, and NPY plus dexamethasone (NPY and dex). Plotted data are means ± SEM of four to seven rats per group. Data were analyzed by two-way ANOVA followed by a posthoc test. *, P < 0.05 vs. vehicle-infused controls.

 


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  		Figure 5. Plasma triglyceride levels in adrenalectomized (ADX) rats at the end of icv infusion of vehicle, dexamethasone alone (dex), NPY alone, and NPY plus dexamethasone (NPY and dex). Plotted data are means ± SEM of four to seven rats per group. Data were analyzed by two-way ANOVA followed by a posthoc test. *, P < 0.05 vs. vehicle-infused controls.

 
The expression of uncoupling proteins was investigated in brown adipose tissue. As shown by Fig. 6Go (upper panel), compared with vehicle-infused ADX rats, UCP1 was markedly decreased by the icv NPY infusion alone, but not any further by the icv NPY plus dexamethasone one (66% and 68% decrease, respectively). A similar observation was made for brown adipose tissue UCP3 expression (Fig. 6Go, lower panel) for which the degree of decrease in expression was similar in the icv NPY-infused ADX group and in the icv NPY plus dexamethasone-infused one (-80 and -78%, respectively).



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  		Figure 6. Uncoupling protein-1 (UCP1, upper panel) and uncoupling protein-3 (UCP3, lower panel) expression in brown adipose tissue in adrenalectomized (ADX) rats after an icv infusion of vehicle, dexamethasone alone (dex), NPY alone, and NPY plus dexamethasone (NPY and dex). At the end of the treatment, brown adipose tissue was removed and total RNA was prepared (for further details, see Materials and Methods). Plotted data are means ± SEM of four to seven rats per group. Data were analyzed by two-way ANOVA followed by a posthoc test. *, P < 0.05 vs. vehicle-infused controls.

 

   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
In rodents, glucocorticoids appear to favor body weight gain, as it has been reported that the obesity-like effects of a chronic icv infusion of neuropeptide Y (NPY) in normal rats could not be observed in adrenalectomized (ADX) rats (22). Furthermore, it has also been shown that glucocorticoids inhibit the "thinning" effect of leptin, a satiety hormone produced by adipose tissue (32). However, the underlying mechanisms of these actions of glucocorticoids remain unsettled.

To further investigate by which means glucocorticoids may promote body weight gain, chronic icv infusion of NPY or of the synthetic glucocorticoid, dexamethasone, respectively, alone or in combination, was carried out in ADX rats. The icv route of dexamethasone administration was chosen as the hypothalamic area plays an important role in the regulation of body weight homeostasis (33).

When considering food intake, it was observed that in ADX rats the combined infusion of NPY and dexamethasone had a tendency to increase food intake. Further, body weight gain of ADX rats receiving an icv infusion of NPY and dexamethasone was markedly increased when compared with control animals. This indicated that the obesifying effects of a central chronic infusion of NPY was restored in presence of dexamethasone.

When infused alone in ADX rats, neither NPY nor dexamethasone was able to favor an insulin or a leptin response. In marked contrast, when combined, the icv infusion of NPY and dexamethasone in ADX rats resulted in marked increases in plasma insulin, triglyceride, and leptin levels relative to vehicle-infused ADX control animals. The combined hyperinsulinemia and hyperlipidemia observed under those conditions was in fact similar to the effect of NPY icv infused in intact rats (34). This dual change was likely to be due to NPY-induced oversecretion of insulin together with enhanced lipogenic activity, with resulting increase in hepatic VLDL output (35). The hyperleptinemia also measured under these conditions is in agreement with the well documented stimulatory effect of insulin on ob gene expression and subsequent leptin secretion (36, 37, 38).

Thus, when considering the stimulatory effects of icv NPY on food intake, body weight, insulin and leptin responses, it appears that they require the presence of central glucocorticoids, with the latter possibly acting at the level of the NPY Y1 and/or Y5 receptor (39, 40) or at subsequent steps.

The present study also shows that not all NPY effects required the presence of central glucocorticoids. Thus, it was striking to observe that the chronic icv infusion of NPY alone in ADX animals resulted in marked decreases in the expression of brown adipose tissue UCP1 (41) and UCP3 (42), decreases that were not further modified by the superimposed infusion of icv dexamethasone. This indicated that, potentially, energy dissipating mechanisms were a genuine target of central NPY that did not require the additional presence of central glucocorticoids. This genuine effect of central (i.e. hypothalamic) NPY could be mediated by a change in the balance of the autonomic nervous system. Thus, as the icv NPY infusion in normal rats has been shown previously to favor the activity of the parasympathetic efferents reaching the pancreas (43), it is possible that increased central NPY levels may increase the activity of other parasympathetic efferents at the expense of sympathetic ones, the latter being implicated in the uncoupling protein-related energy dissipating processes (44, 45, 46). This view would be in agreement with data showing that central NPY administration in normal rats suppresses in a dose-dependent manner the sympathetic activity of nerves innervating the brown adipose tissue (47).

Although both NPY and dexamethasone have been, in the present study, administered centrally, one cannot rule out that they may have leaked into the peripheral circulation. One should note, however, that NPY produces obesity-like changes only when administered centrally (48, 49). Moreover, in adrenalectomized animals, it has been previously shown that icv injections of glucocorticoids augmented food intake and body weight, all at doses that had no effect when administered peripherally (50, 51). Finally, when given at a same dosage centrally vs. peripherally to normal rats, dexamethasone has been found to stimulate or inhibit food intake and body weight gain, respectively (52). Thus, the combined effects of icv NPY plus dexamethasone infusion are likely to be centrally elicited.

To conclude, the present study shows that many of the effects elicited by central NPY infusion require the presence of central glucocorticoids, as they do not occur when the neuropeptide is infused singly in ADX rats but become apparent when the ADX rats are simultaneously infused with icv NPY and with icv dexamethasone. These glucocorticoid-requiring NPY effects bear on the neuronal pathways that stimulate food intake, insulin secretion, and related changes favoring anabolic processes and fat deposition. However, some icv NPY-triggered effects do not have such requirement for glucocorticoids: icv infusion of NPY alone decreases the expression of uncoupling proteins without further influence of the superimposed dexamethasone infusion. This suggests that neuropeptide Y may in itself and ultimately diminish the energy dissipating mechanisms. The existence of glucocorticoid-requiring and nonglucocorticoid-requiring effects of icv neuropeptide Y infusion underlines the complexity of the role of these hormones in the regulation of body weight homeostasis, and/or in the evolution toward obesity.


   Acknowledgments
 
We like to thank F. Pralong for his help with the CRH RIA. We are grateful to P. Arboit, P. German, and A. Volery (L.R.M.), and to G. Monnet (Novartis) for their skillful technical assistance.


   Footnotes
 
1 This research has been supported by grant No. 31–53719.98 of the Swiss National Science Foundation (Bern, Switzerland) and by a grant-in-aid from Novartis Pharma AG (Basle, Switzerland). Back

Received September 22, 1998.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Freedman MR, Castonguay TW, Stern JS 1985 Effect of adrenalectomy and corticosterone replacement on meal patterns of Zucker rats. Am J Physiol 249:R584–R594
  2. Freedman MR, Horwitz BA, Stern JS 1986 Effect of adrenalectomy and glucocorticoid replacement on development of obesity. Am J Physiol 250:R595–R607
  3. Castonguay TW, Dallman MF, Stern JS 1986 Some metabolic and behavioral effects of adrenalectomy on obese Zucker rats. Am J Physiol 251:R923–R933
  4. Fletcher JM, McKenzie N 1988 The parasympathetic nervous system and glucocorticoid-mediated hyperinsulinaemia in the genetically obese (fa/fa) Zucker rat. J Endocrinol 118:87–92[Abstract/Free Full Text]
  5. Walker HC, Romsos DR 1992 Glucocorticoids in the CNS regulate BAT metabolism and plasma insulin in ob/ob mice. Am J Physiol 262:E110–E117
  6. Sanacora G, Kershaw M, Finkelstein JA, White JD 1990 Increased hypothalamic content of preproneuropeptide Y messenger ribonucleic acid in genetically obese Zucker rats and its regulation by food deprivation. Endocrinology 127:730–737[Abstract/Free Full Text]
  7. Williams G, Shellard L, Lewis DE, McKibbin PE, McCarthy HD, Koeslag G, Russell JC 1992 Hypothalamic neuropeptide Y disturbances in the obese (cp/cp)JCR:LA corpulent rat. Peptides 13:537–540[CrossRef][Medline]
  8. Beck B, Burlet A, Bazin R, Nicolas JP, Burlet C 1993 Elevated neuropeptide-Y in the arcuate nucleus of young obese Zucker rats may contribute to the development of their overeating. J Nutr 123:1168–1172
  9. Bchini-Hooft van Huijsduijnen O, Rohner-Jeanrenaud F, Jeanrenaud B 1993 Hypothalamic neuropeptide Y messenger ribonucleic acid levels in pre-obese and genetically obese (fa/fa) rats; potential regulation thereof by corticotropin-releasing factor. J Neuroendocrinol 5:381–386[CrossRef][Medline]
  10. Wilding JPH, Gilbey SG, Bailey CJ, Batt RAL, Williams G, Ghatei MA, Bloom SR 1993 Increased neuropeptide-Y messenger and decreased neurotensin messenger RNA in the hypothalamus of the obese (ob/ob) mouse. Endocrinology 132:1939–1944[Abstract/Free Full Text]
  11. Clark JT, Kalra PS, Crowley WR, Kalra SP 1984 Neuropeptide Y and human pancreatic polypeptide stimulate feeding behavior in rats. Endocrinology 115:427–429[Abstract/Free Full Text]
  12. Stanley BG, Kyrkouli SE, Lampert S, Leibowitz SF 1986 Neuropeptide Y chronically injected into the hypothalamus: a powerful neurochemical inducer of hyperphagia and obesity. Peptides 7:1189–1192[CrossRef][Medline]
  13. Zarjevski N, Cusin I, Vettor R, Rohner-Jeanrenaud F, Jeanrenaud B 1994 Intracerebroventricular administration of neuropeptide Y to normal rats has divergent effects on glucose utilization by adipose tissue and skeletal muscle. Diabetes 43:764–769[Abstract]
  14. Leibowitz SF 1995 Brain peptides and obesity: pharmacologic treatment. Obes Research 3:573s–589s[Medline]
  15. Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, Williams SC, Richardson JA, Kozlowski GP, Wilson S, Arch JRS, Buckingham RE, Haynes AC, Carr SA, Annan RS, McNulty DE, Liu W-S, Terrett JA, Elshourbagy NA, Bergsma DJ, Yanagisawa M 1998 Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92:573–585[CrossRef][Medline]
  16. Flier JS, Maratos-Flier E 1998 Obesity and the hypothalamus: novel peptides for the new pathways. Cell 92:437–440[CrossRef][Medline]
  17. Woods SC, Seeley RJ, Porte Jr D, Schwartz MW 1998 Signals that regulate food intake and energy homeostasis. Science 280:1378–1382[Abstract/Free Full Text]
  18. Chen H, Charlat O, Tartaglia LA, Woolf EA, Weng X, Ellis SJ, Lakey ND, Culpepper J, Moore KJ, Breitbart RE, Duyk GM, Tepper RI, Morgenstern JP 1996 Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db/db mice. Cell 84:491–495[CrossRef][Medline]
  19. Chua SC Jr, Chung WK, Wu-Peng XS, Zhang Y, Liu SM, Tartaglia L, Leibel RL 1996 Phenotypes of mouse diabetes and rat fatty due to mutations in the OB (leptin) receptor. Science 271:994–996[Abstract]
  20. Lee G-H, Proenca R, Montez JM, Carroll KM, Darvishzadeh JG, Lee JI, Friedman JM 1996 Abnormal splicing of the leptin receptor in diabetic mice. Nature 379:632–635[CrossRef][Medline]
  21. Phillips MS, Liu Q, Hammond HA, Dugan V, Hey PJ, Caskey CJ, Hess JF 1996 Leptin receptor missense mutation in the fatty Zucker rat. Nat Genet 13:18–19[CrossRef][Medline]
  22. Sainsbury A, Cusin I, Rohner-Jeanrenaud F, Jeanrenaud B 1997 Adrenalectomy prevents the obesity syndrome produced by chronic central neuropeptide Y infusion in normal rats. Diabetes 46:209–214[Abstract]
  23. Harfstrand A, Cintra A, Fuxe K, Aronsson M, Wikstrom AC, Okret S, Gustafsson JA, Agnati LF 1989 Regional differences in glucocorticoid receptor immunoreactivity among neuropeptide Y immunoreactive neurons of the rat brain. Acta Physiol Scand 135:3–9[Medline]
  24. Larsen PJ, Jessop DS, Chowdrey HS, Lightman SL, Mikkelsen JD 1994 Chronic administration of glucocorticoids directly upregulates prepro-neuropeptide Y and Y1-receptor mRNA levels in the arcuate nucleus of the rat. J Neuroendocrinol 6:153–159[CrossRef][Medline]
  25. Tempel DL, Leibowitz SF 1993 Glucocorticoid receptors in PVN: interactions with NE, NPY, and Gal in relation to feeding. Am J Physiol 265:E794–E800
  26. Tempel DL, Leibowitz SF 1994 Adrenal steroid receptors: interactions with brain neuropeptide systems in relation to nutrient intake and metabolism. J Neuroendocrinol 6:479–501[CrossRef][Medline]
  27. Tanaka J, Nomura M 1993 Involvement of neurons sensitive to angiotensin II in the median preoptic nucleus in the drinking response induced by angiotensin II activation of the subfornical organ in rats. Exp Neurol 119:235–239[CrossRef][Medline]
  28. Gwosdow-Cohen A, Chen CL, Besch EL 1982 Radioimmunoassay (RIA) of serum corticosterone in rats. Proc Soc Exp Biol Med 170:29–34[CrossRef][Medline]
  29. Tempel DL, McEwen BS, Leibowitz SF 1993 Adrenal steroid receptors in the PVN: studies with steroid antagonists in relation to macronutrient intake. Neuroendocr 57:1106–1113
  30. Herbert V, Lau KS, Gottlieb CW, Bleicher SJ 1965 Coated charcoal immunoassay of insulin. J Clin Endocrinology 25:1375–1384
  31. Cusin I, Zakrzewska KE, Boss O, Muzzin P, Giacobino JP, Ricquier D, Jeanrenaud B, Rohner-Jeanrenaud F 1998 Chronic central leptin infusion enhances insulin-stimulated glucose metabolism and favors the expression of uncoupling proteins. Diabetes 47:1014–1019[Abstract]
  32. Zakrzewska KE, Cusin I, Sainsbury A, Rohner-Jeanrenaud F, Jeanrenaud B 1997 Glucocorticoids as counterregulatory hormones of leptin: toward and understanding of leptin resistance. Diabetes 46:717–719[Abstract]
  33. Rohner-Jeanrenaud F 1995 A neuroendocrine reappraisal of the dual-centre hypothesis: its implications for obesity and insulin resistance. Int J Obes 19:517–534[Medline]
  34. Zarjevski N, Cusin I, Vettor R, Rohner-Jeanrenaud F, Jeanrenaud B 1993 Chronic intracerebroventricular neuropeptide-Y administration to normal rats mimics hormonal and metabolic changes of obesity. Endocrinology 133:1753–1758[Abstract/Free Full Text]
  35. Jeanrenaud B 1994 Central nervous system and peripheral abnormalities: clues to the understanding of obesity and NIDDM. Diabetologia 37:S169–S178
  36. Saladin R, De Vos P, Guerre-Millo M, Leturque A, Girard J, Staels B, Auwerx J 1995 Transient increase in obese gene expression after food intake or insulin administration. Nature 377:527–529[CrossRef][Medline]
  37. Cusin I, Sainsbury A, Doyle P, Rohner-Jeanrenaud F, Jeanrenaud B 1995 The ob gene and insulin. A relationship leading to clues to the understanding of obesity. Diabetes 44:1467–1470[Abstract]
  38. Leroy P, Dessolin S, Villageois P, Moon BC, Friedman JM, Aihauld G, Dani C 1996 Expression of ob gene in adipose cells. Regulation by insulin. J Biol Chem 271:2365–2368[Abstract/Free Full Text]
  39. Wahlestedt C, Reis DJ 1993 Neuropeptide Y-related peptides and their receptors—are the receptors potential therapeutic drug targets? Ann Rev Pharmacol Toxicol 32:309–352[CrossRef]
  40. Gerald C, Walker MW, Criscione L, Gustafson EL, Batzl-Hartmann C, Smith KE, Vaysse P, Durkin MM, Laz TM, Linemeyer DL, Schaffhauser AO, Whitebread S, Hofbauer KG, Taber RI, Branchek TA, Weinshank RL 1996 A receptor subtype involved in neuropeptide-Y-induced food intake. Nature 382:168–171[CrossRef][Medline]
  41. Bouillaud F, Wissenbach J, Ricquier D 1986 Complete cDNA-derived amino acid sequence of rat brown fat uncoupling protein. J Biol Chem 261:1487–1490[Abstract/Free Full Text]
  42. Boss O, Samec S, Paoloni-Giacobino A, Rossier C, Dulloo A, Seydoux J, Muzzin P, Giacobino JP 1997 Uncoupling protein-3:a new member of the mitochondrial carrier family with tissue-specific expression. FEBS Lett 408:39–42[CrossRef][Medline]
  43. Sainsbury A, Rohner-Jeanrenaud F, Cusin I, Zakrzewska KE, Halban PA, Gaillard RC, Jeanrenaud B 1997 Chronic central neuropeptide Y infusion in normal rats: status of the hypothalamo-pituitary-adrenal axis, and vagal mediation of hyperinsulinemia. Diabetologia 40:1269–1277[CrossRef][Medline]
  44. Onai T, Kilroy G, York DA, Bray GA 1995 Regulation of ß 3-adrenergic receptor mRNA by sympathetic nerves and glucocorticoids in BAT of Zucker obese rats. Am J Physiol 269:R519–R526
  45. Geloen A, Trayhurn P 1990 Regulation of the level of uncoupling protein in brown adipose tissue by insulin requires the mediation of the sympathetic nervous system. FEBS Lett 267:265–267[CrossRef][Medline]
  46. Larkin S, Mull E, Miao W, Pittner R, Albrandt K, Moore C, Young A, Denaro M, Beaumont K 1997 Regulation of the third member of the uncoupling protein family, UCP3, by cold and thyroid hormone. Biochem Biophys Res Commun 240:222–227[CrossRef][Medline]
  47. Egawa M, Yoshimatsu H, Bray GA 1991 Neuropeptide Y suppresses sympathetic activity to interscapular brown adipose tissue in rats. Am J Physiol 260:R328–R334
  48. Waeber B, Aubert J-F, Corder R, Nussberger J, Gaillard R, Brunner HR 1988 Cardiovascular effects of neuropeptide Y. Am J Hypertens 1:193–199[Medline]
  49. Skoglund G, Gross R, Ahrèn B, Loubatières-Mariani MM 1993 Different mechanisms are involved in neuropeptide Y-induced pancreatic vasoconstriction and inhibition of insulin secretion. Eur J Pharmacol 236:69–74[CrossRef][Medline]
  50. Green PK, Wilkinson CW, Woods SC 1992 Intraventricular corticosterone increases the rate of body weight gain in underweight adrenalectomized rats. Endocrinology 130:269–275[Abstract/Free Full Text]
  51. Debons AF, Zurek LD, Tse CS, Abrahamsen S 1986 Central nervous system control of hyperphagia in hypothalamic obesity: dependence on adrenal glucocorticoids. Endocrinology 118:1678–1681[Abstract/Free Full Text]
  52. Zakrzewska KE, Cusin I, Stricker-Krongrad A, Boss O, Ricquier D, Jeanrenaud B, Rohner-Jeanrenaud F 1999 Induction of obesity and hyperleptinemia by central glucocorticoid infusion in the rat. Diabetes 48:365–370



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