B Jeanrenaud

University of Geneva, Genève, Geneva, Switzerland

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Publications (277)1158.54 Total impact

  • E. BOBBIONI-HARSCH, B. JEANRENAUD
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    ABSTRACT: . Hypothalamic extract from normal rats was shown to contain a principle able to stimulate insulin secretion both in vivo and in vitro.This substance, whose peptidic nature was demonstrated by enzymatic digestion, has a molecular weight of about 1000 Daltons. An active release of this peptide was obtained when incubating hypothalamic fragments under appropriate stimulatory conditions (i.e. KC1 50 mmol 1-1 in the incubation medium) (i.e. molecular weight and insulin secretion stimulating activity) similar to the hypothalamic peptide was evidentiated in the plasma of normal rats. Since manipulations of hte hypothalamus (i.e. electrical lesions or stimulations) could respectively decrease or enhance the plasma concentration of this substance, the hypothalamic origin of the insulin secretion stimulating principle present in the plasma was strongly suggested. The possible participation of this hypothalamic peptide to the neural control of insulin secretion is suggested.
    European Journal of Clinical Investigation 01/2008; 20(1):18-19. · 3.37 Impact Factor
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    ABSTRACT: Neuropeptide Y (NPY) synthesized in the arcuato-paraventricular projection in the rat hypothalamus is thought to play an important role in controlling energy homeostasis. The factors that regulate hypothalamic NPY are not known but, amongst others, insulin has been postulated as an inhibitory modulatory agent. To test this hypothesis, normal male rats were given either insulin (2 units/day) or saline via subcutaneous osmotic minipumps for 3 days. Euglycaemia was maintained by a concomitant glucose infusion in insulin-infused rats which had peripheral insulin levels 5–8 times higher than saline-infused controls. Hyperinsulinaernic rats ate 42% less than controls, but their total energy intake (food intake plus glucose infusion) was higher than that of controls, and they gained more weight than controls during the experimental period. Hyperinsulinaemia had no significant effect on hypothalamic NPY mRNA or NPY levels in the arcuate nucleus. NPY concentrations in the paraventricular nucleus were, however, significantly increased by 73% in hyperinsulinaemic rats, but were closely similar to controls in all other areas. Insulin may act as a satiety factor in that hyperinsulinaemic rats ate less, but the fact that these animals had increased total energy intake and gained excessive weight suggests that insulin may not function as an overall regulator of energy balance. In addition, physiological hyperinsulinaemia does not apparently inhibit NPY gene expression in the arcuate nucleus. Due to the lack of effect of hyperinsulinaemia on NPY synthesis in the arcuate nucleus, the elevated NPY concentrations in the paraventricular nucleus could result from a reduction of its release, which would be in keeping with the reduction in food intake.
    Journal of Neuroendocrinology 09/2006; 7(3):193 - 197. · 3.33 Impact Factor
  • Bernard Jeanrenaud, Françoise Rohner-Jeanrenaud
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    ABSTRACT: Body weight homeostasis is maintained via interactions between the brain and the periphery, mediated by a hormone, leptin, synthesized in adipose tissue. Secreted leptin crosses the blood-brain barrier and binds to a receptor in the hypothalamus, leading to inhibition of orexigenic neuropeptides and stimulation of the effects of anorexigenic ones. Leptin thereby decreases food intake and increases fat oxidation and energy expenditure. The characteristics of the main orexigenic peptides, neuropeptide Y, melanin concentrating hormone, orexins A and B and opioids, and the effects of leptin thereon are summarized. Anorexigenic peptides include the cocaine- and amphetamine-regulated transcript, a hypothalamic peptide that is regulated by leptin and suppresses appetite. Corticotropin-releasing hormone decreases food intake and increases metabolic activity. The melanocortin system also decreases food intake and a role for leptin in influencing this process is discussed. Most of the studies described were in animals but the pathways are present in people and may provide a means to control at least some aspects of human obesity.
    01/2002: pages 99 - 112; , ISBN: 9780470846735
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    B Jeanrenaud, F Rohner-Jeanrenaud
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    ABSTRACT: Body weight homeostasis is maintained via a series of complex interactions that occur between the brain (particularly the hypothalamus) and the periphery, notably via the hormone leptin, which is synthesized in and secreted from adipose tissue. Under normal conditions, a dynamic equilibrium exists between anabolic neuropeptides (orexigenic peptides), which favor food intake, decrease energy expenditure, and facilitate fat storage, and catabolic ones (anorexigenic peptides), which decrease food intake, increase energy expenditure, and facilitate the loss of fat stores. Secreted leptin, although it may have some direct peripheral effects, exerts its action principally within the brain. Following its transport through the blood-brain barrier, leptin reaches the hypothalamic area, where it binds to its long receptor isoform. After a specific signaling cascade, leptin inhibits many of the orexigenic neuropeptides while favoring many of the anorexigenic ones. Thus, leptin decreases food intake and body weight, and it increases fat oxidation and energy expenditure, ultimately favoring leanness. Lack of leptin secretion, the inability of leptin to reach the brain, or the inability of leptin to interact with hypothalamic leptin receptors, prevent leptin's effects and lead to obesity.
    Annual Review of Medicine 02/2001; 52:339-51. · 14.60 Impact Factor
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    B Jeanrenaud, F Rohner-Jeanrenaud
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    ABSTRACT: The obesity-like effects produced by the chronic intracerebroventricular (i.c.v.) neuropeptide Y (NPY) infusion in normal rats require the presence of glucocorticoids, as none of them occurs when NPY is similarly infused in adrenalectomized rats. NPY effects are present again when i.c.v. NPY is infused together with i.c.v. dexamethasone in adrenalectomized animals. The inhibitory effect of leptin on food intake and body weight observed when the hormone is i.c.v. administered to normal rats is markedly enhanced and longer lasting when the same dose of leptin is i.c.v. administered to adrenalectomized rats. Glucocorticoid administration to adrenalectomized rats dose-dependently reduces, then abolishes, this potent effect of leptin. Thus, glucocorticoids limit leptin-induced effects. The chronic i.c.v. infusion of glucocorticoids (dexamethasone) to normal rats produces an obesity syndrome with its several abnormalities. This appears to be due to glucocorticoid-elicited increases in hypothalamic NPY levels together with decreases in those of CRH. Thus, the status of the hypothalamo-pituitary-adrenal axis and related glucocorticoid output is a relevant facet of body weight homeostasis. It may be a deleterious environmental factor responsible for the development of obesity, insulin as well as leptin resistance, and type 2 diabetes.
    International Journal of Obesity 07/2000; 24 Suppl 2:S74-6. · 5.22 Impact Factor
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    ABSTRACT: Centrally administered leptin has been shown to increase insulin-stimulated glucose utilization and to favor the expression of uncoupling proteins (UCPs). To study if leptin also has direct peripherally mediated effects on these processes, this hormone (1 mg/day) or its vehicle was infused i.v. for 4 days to lean rats and insulin-stimulated glucose utilization in skeletal muscle and adipose tissue as well as the expression of UCP messenger RNAs (mRNAs) in brown adipose tissue were measured. I.v. leptin administration resulted in decreases in food intake (31%), body weight gain, and plasma insulin levels (45%), in increases in overall (23%) as well as brown adipose tissue and muscle glucose utilization, and in decreases in white adipose tissue glucose uptake. Most of these changes were mimicked, in control rats, by giving them the same amount of food as that consumed by the leptin-infused group (pair-feeding). I.v. leptin infusion also favored the expression of UCPs in brown adipose tissue, either by increasing their expression or preventing the fall occurring during the pair-feeding regimen. Relative UCP expression levels were 100, 104, and 33 for UCP1, 100, 191, and 125 for UCP2 and 100, 107, and 29 for UCP3 in ad libitum fed control rats, in leptin-treated rats and in pair-fed control rats, respectively. These results suggest that the overall effect of leptin on glucose utilization and on the expression of UCPs may be mediated through central mechanism.
    Endocrinology 09/1999; 140(8):3688-92. · 4.72 Impact Factor
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    ABSTRACT: 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 i.c.v. NPY infusion in ADX rats receiving or not i.c.v. glucocorticoids. It was found that the combined i.c.v. 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.
    Endocrinology 08/1999; 140(7):3183-7. · 4.72 Impact Factor
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    ABSTRACT: It has been claimed that factors favoring the development or maintenance of animal or human obesity may include increases in glucocorticoid production or hyperresponsiveness of the hypothalamic-pituitary-adrenal axis. In normal rats, glucocorticoids have been shown to be necessary for chronic intracerebroventricular infusion of neuropeptide Y to produce obesity and related abnormalities. Conversely, glucocorticoids inhibited the body weight-lowering effect of leptin. Such dual action of glucocorticoids may occur within the central nervous system, since both neuropeptide Y and leptin act within the hypothalamus. The aim of this study was to determine the effects of glucocorticoids (dexamethasone) given intracerebroventricularly to normal rats on body weight homeostasis and hypothalamic levels of neuropeptide Y and corticotropin-releasing hormone. Continuous central glucocorticoid infusion for 3 days resulted in marked sustained increases in food intake and body weight relative to saline-infused controls. The infusion abolished endogenous corticosterone output and produced hyperinsulinemia, hypertriglyceridemia, and hyperleptinemia, three salient abnormalities of obesity syndromes. Central glucocorticoid infusion also produced a marked decrease in the expression of uncoupling protein (UCP)-1 and UCP-3 in brown adipose tissue and UCP-3 in muscle. Finally, chronic central glucocorticoid administration increased the hypothalamic levels of neuropeptide Y and decreased those of corticotropin-releasing hormone. When the same dose of glucocorticoids was administered peripherally, it resulted in decreases in food intake and body weight, in keeping with the decrease in hypothalamic neuropeptide Y levels. These results suggest that glucocorticoids induce an obesity syndrome in rodents by acting centrally and not peripherally.
    Diabetes 03/1999; 48(2):365-70. · 7.90 Impact Factor
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    ABSTRACT: Intracerebroventricular administration of neuropeptide Y to normal rats induces a syndrome characterised by obesity, hyperinsulinaemia, insulin resistance and over expression of the adipose tissue ob gene. Little is known about the effect of circulating neuropeptide Y on glucose metabolism, insulin secretion and leptin. We therefore aimed to evaluate the effect of an intravenous infusion of neuropeptide Y on glucose disposal, endogenous glucose production, whole body glycolytic flux, and glucose storage as assessed during euglycaemic hyperinsulinaemic clamp. In addition, the insulin-stimulated glucose utilisation index in individual tissues was measured by the 2-deoxy-[1-3H]-glucose technique. The effect of neuropeptide Y on insulin secretion was evaluated by hyperglycaemic clamp. Infusion did not induce any change in endogenous glucose production during basal conditions or at the end of the clamp. Glucose disposal was significantly increased in the rats given neuropeptide Y compared with controls (27.8 +/- 1.3 vs 24.3 +/- 1.6 mg x min(-1) x kg(-1); p < 0.05) as was the glycolytic flux (18.9 +/- 1.6 vs 14.4 +/- 0.8 mg x min(-1) x kg(-1); p < 0.05), while glucose storage was comparable in the two groups. In skeletal muscle, the glucose utilisation index was increased significantly in rats given neuropeptide Y. The glucose utilisation index in subcutaneous and epididimal adipose tissue was not significantly different between the two groups. Plasma leptin was significantly increased by hyperinsulinaemia, but was not affected by neuropeptide Y infusion. Both the early and late phase of the insulin response to hyperglycaemia were significantly reduced by neuropeptide Y. In conclusion neuropeptide Y infusion may increase insulin-induced glucose disposal in normal rats, accelerating its utilisation through the glycolytic pathway. Neuropeptide Y reduces both phases of the insulin response to hyperglycaemia.
    Diabetologia 12/1998; 41(11):1361-7. · 6.49 Impact Factor
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    ABSTRACT: Continuous (4 days) intracerebroventricular leptin infusion (12 microg/day) was performed in lean rats, and its hormonometabolic effects were determined. Intracerebroventricular leptin administration did not result in leakage of the hormone into the peripheral circulation. Thus, its effects were elicited by its presence within the central nervous system. Intracerebroventricular leptin infusion produced marked decreases in food intake and body weight gain relative to vehicle-infused fed ad libitum rats. Because decreases in food intake alter hormonometabolic homeostasis, additional control rats pair-fed to the amount of food consumed by leptin-infused ones were included in the study. Intracerebroventricular leptin-infused and vehicle-infused pair-fed rats were characterized, relative to vehicle-infused ad libitum-fed animals, by decreases in body weight and insulinemia and by increases in insulin-stimulated overall glucose utilization and muscle and brown adipose tissue glucose utilization index. Brown adipose tissue uncoupling protein (UCP)1, UCP2, and UCP3 mRNA levels were markedly decreased in pair-fed animals relative to those of fed ad libitum control animals, as were liver and white adipose tissue UCP2 and muscle UCP3 mRNA levels. In marked contrast, intracerebroventricular leptin administration was accompanied by the maintenance of high UCP1, UCP2, and UCP3 expression in all these tissues. Thus, despite analogies between leptin's effects and those of pair-feeding with regard to glucose handling, their respective underlying mechanisms differ. While leptin maintains or favors energy-dissipating mechanisms (UCP1, UCP2, and UCP3), the latter are markedly depressed in pair-fed rats. This effect of leptin may prevent subsequent excessive storage processes, thereby maintaining normal body homeostasis.
    Diabetes 08/1998; 47(7):1014-9. · 7.90 Impact Factor
  • B Jeanrenaud, I Cusin, F Rohner-Jeanrenaud
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    ABSTRACT: The concept of interrelationships between the central nervous system and the periphery aimed at maintaining normal body weight homeostasis has been strengthened by the discovery of hypothalamic neuropeptide Y (NPY) and adipose tissue leptin. NPY, when infused intracerebroventricularly in normal animals produces hyperphagia and hormono-metabolic changes (hyperinsulinemia, hypercorticism) channeling nutrients preferentially toward lipogenesis and storage in adipose tissue and away from their utilization by muscles (muscle insulin resistance). Storage in NPY-infused rats is further favored by the observed decrease in the expression of uncoupling proteins. NPY-induced hyperinsulinemia and hypercorticosteronemia also promote leptin over-secretion. Released leptin, acting within the hypothalamus, decreases hypothalamic NPY levels (probably those of other hypothalamic neuropeptides as well), food intake, insulinemia, insulin sensitivity of white adipose tissue, while increasing that of muscles. Leptin acting centrally additionally favors the expression of uncoupling protein 1, 2, and 3, in keeping with an eflect on energy dissipating mechanisms. The respective hormono-metabolic eflects of NPY and leptin maintain a normal body homeostasis. In most obesity syndromes, the functional relationships between NPY and leptin are altered. Due to hypothalamic leptin receptor mutations or dysfunctions, leptin cannot exert its eflects: NPY levels (possibly those of other neuropeptides) remain elevated, maintaining excess storage, insulin as well as leptin resistance.
    Comptes rendus des séances de la Société de biologie et de ses filiales 02/1998; 192(5):829-41.
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    ABSTRACT: Neuropeptide Y in the hypothalamus is a potent physiological stimulator of feeding, and may contribute to the characteristic metabolic defects of obesity when hypothalamic levels remain chronically elevated. Since corticosterone and insulin are important regulators of fuel metabolism, the longitudinal effects of chronic (6 days) intracerebroventricular infusion of neuropeptide Y in normal rats on the hypothalamo-pituitary-adrenal axis and on insulin secretion were studied. Neuropeptide Y-infused rats were either allowed to eat ad libitum, or were pair-fed with normophagic control rats. Neuropeptide Y increased the basal plasma concentrations of adrenocorticotropic hormone and corticosterone during the first 2 days of its intracerebroventricular infusion and increased cold stress-induced plasma adrenocorticotropic hormone concentrations. After 4-6 days of central neuropeptide Y infusion, however, basal plasma adrenocorticotropic hormone and corticosterone concentrations were no different from control values (except in ad libitum-fed rats in which corticosteronaemia remained elevated), they were unaffected by the stress of cold exposure, and the hypothalamic content of corticotropin-releasing factor immunoreactivity was significantly decreased. A state of hyperinsulinaemia was present throughout the 6 days of intracerebroventricular neuropeptide Y infusion, being more marked in the ad libitum-fed than in the pair-fed group. The proportions of insulin, proinsulin, and conversion intermediates in plasma and pancreas were unchanged. Hyperinsulinaemia of the pair-fed neuropeptide Y-infused rats was accompanied by muscle insulin resistance and white adipose tissue insulin hyperresponsiveness, as assessed by the in vivo uptake of 2-deoxyglucose. Finally, bilateral subdiaphragmatic vagotomy prevented both the basal and the marked glucose-induced hyperinsulinaemia of animals chronically infused with neuropeptide Y, demonstrating that central neuropeptide Y-induced hyperinsulinaemia is mediated by the parasympathetic nervous system.
    Diabetologia 12/1997; 40(11):1269-77. · 6.49 Impact Factor
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    ABSTRACT: Plasma lactate is elevated in many physiological and pathological conditions, such as physical exercise, obesity, and diabetes, in which a reduction of insulin sensitivity is also present. Furthermore, an increased production of lactate from muscle and adipose tissue together with increased gluconeogenic substrate flux to the liver plays a primary role in enhancing hepatic glucose production (HGP) in diabetes. It has been shown that lactate may interfere with the utilization and oxidation of other substrates such as free fatty acids (FFAs). The aim of this study was to investigate if lactate infusion affects peripheral glucose utilization in rats. Animals were acutely infused with lactate to achieve a final lactate concentration of 4 mmol/L. They were then submitted to a euglycemic-hyperinsulinemic clamp to study HGP and overall glucose metabolism (rate of disappearance [Rd]). At the end of the clamp, a bolus of 2-deoxy-[1-3H]-glucose was injected to study insulin-dependent glucose uptake in different tissues. The results show that lactate infusion did not affect HGP either in the basal state or at the end of clamp, whereas glucose utilization significantly decreased in lactate-infused rats (26.6 +/- 1.1 v 19.5 +/- 1.4 mg.kg-1.min-1, P < .01). A reduction in the tissue glucose utilization index was noted in heart (18.01 +/- 4.44 v 46.21 +/- 6.51 ng.mg-1.min-1, P < .01), diaphragm (5.56 +/- 0.74 v 9.01 +/- 0.93 ng.mg-1.min-1, P < .01), soleus (13.62 +/- 2.29 v 34.05 +/- 6.08 ng.mg-1.min-1, P < .01), and red quadricep (4.43 +/- 0.73 v 5.88 +/- 0.32 ng.mg-1.min-1, P < .05) muscle in lactate-infused animals, whereas no alterations were observed in other muscles or in adipose tissue. Therefore, we suggest that acute lactate infusion induces insulin resistance in the heart and some muscles, thus supporting a role for lactate in the regulation of peripheral glucose metabolism.
    Metabolism 07/1997; 46(6):684-90. · 3.10 Impact Factor
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    ABSTRACT: The product of the ob gene, leptin, is a hormone secreted by adipose tissue that acts in the hypothalamus to regulate the size of the body fat depot. Its central administration has been shown to decrease food intake and body weight, while favoring energy dissipation. As glucocorticoids are known to play a permissive role in the establishment and maintenance of obesity syndromes in rodents, it was hypothesized that they do so by restraining the effect of leptin. Leptin injected intracerebroventricularly as a bolus of 3 microg in normal rats induced modest reductions in body weight and food intake. In marked contrast, the same dose of leptin had very potent and long-lasting effects in decreasing both body weight and food intake when administered to adrenalectomized rats. Further, glucocorticoid supplementation of adrenalectomized rats dose-dependently inhibited these potent effects of leptin. These data suggest that glucocorticoids play a key inhibitory role in the action of leptin. Under normal conditions, this inhibitory influence of glucocorticoids may prevent lasting hypophagia. In obesity with degrees of hypercorticism, it may contribute to "leptin resistance," whose etiology is still little understood.
    Diabetes 05/1997; 46(4):717-9. · 7.90 Impact Factor
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    ABSTRACT: Resting, post-absorptive endogenous glucose production (EGP), fractional gluconeogenesis and liver glycogen concentration were assessed in 6 lean and 5 obese non-diabetic subjects undergoing elective abdominal surgery. During the 2 days preceding these measurements, 0.3 g/day U-13C glucose had been added to their usual diet to label their endogenous glycogen stores. On the morning of day 3, EGP was measured with 6,6-2H glucose. Their endogenous 13C glycogen enrichment was calculated from 13CO2 and respiratory gas exchanges. Fractional gluconeogenesis was assessed as 1-(13C glucose/13C glycogen)100. EGP was similar in lean subjects (113 +/- 5 mg/min) and in obese subjects (111 +/- 6). Fractional gluconeogenesis was higher in obese (59 +/- 10%) than in lean subjects (29 +/- 8%). However, overall EGP remained constant due to a decrease in glycogenolysis. Since an increased gluconeogenesis and a decreased glycogenolysis may both contribute to increase liver glycogen concentration in obesity, hepatic glycogen concentrations were assessed in hepatic needle biopsies obtained during surgery. Hepatic glycogen concentrations were increased in obese patients (515 +/- 38 mg/g protein) compared to lean subjects (308 +/- 58, p < 0.05). It is concluded that in obese patients: a) fractional gluconeogenesis is increased; b) overall EGP is unchanged due to a proportional inhibition of glycogenolysis; c) liver glycogen concentration is increased.
    Diabetologia 04/1997; 40(4):463-8. · 6.49 Impact Factor
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    ABSTRACT: Neuropeptide Y (NPY) in the hypothalamus plays an important role in the regulation of food intake and body weight and seems to be implicated in the etiology of obesity. When intracerebroventricularly (ICV) infused for 6 days in normal rats, NPY resulted in hyperphagia, increased body weight gain, hyperinsulinemia, hypercorticosteronemia, and hypertriglyceridemia compared with vehicle-infused control rats. NPY infusion also resulted in an insulin-resistant state in muscles and in a state of insulin hyperresponsiveness in white adipose tissue, as assessed by the measurement of the in vivo glucose utilization index of these tissues during euglycemic-hyperinsulinemic clamps. All of these hormono-metabolic effects produced by chronic central NPY infusion were completely prevented when rats were adrenalectomized before NPY administration. Adrenalectomy per se had no effect on any of the parameters mentioned above. The levels of mRNA for the obese gene were increased in white adipose tissue after 6 days of ICV NPY infusion in normal rats, and white adipose tissue weight was also increased. These effects of ICV NPY infusion were markedly decreased by prior adrenalectomy, although NPY infusion was able to somewhat enhance the low white adipose tissue obese mRNA levels and tissue weight of adrenalectomized rats. In conclusion, intact adrenal glands, and probably circulating corticosterone in particular, are necessary for the establishment of most of the hormonal and metabolic effects induced by chronic ICV infusion of NPY in normal rats.
    Diabetes 03/1997; 46(2):209-14. · 7.90 Impact Factor
  • E Rohner-Jeanrenaud, B Jeanrenaud
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    ABSTRACT: The discovery of both neuropeptide Y and of leptin has led to a better understanding of the pathophysiology of obesity syndromes in animal models. It has strengthened the concept of the importance of the hypothalamus in the etiology of these syndromes. Due to alterations in the regulation of the hypothalamus, e.g. by insulin, by leptin or by decreases in the availability of glucose in specific brain areas, most animal models of obesity have higher than normal hypothalamic neuropeptide Y levels. As neuropeptide Y is a potent orexigenic agent, this hypothalamic defect explains why obese rodents are hyperphagic. Increased hypothalamic neuropeptide Y levels produce hyperinsulinemia and hypercorticism, two abnormalities previously reported in obesity, but whose origin is now known to be driven by neuropeptide Y. As hyperinsulinemia favors lipid accretion and muscle insulin resistance, and as hypercorticism favors the occurrence of both high circulating triglyceride levels and muscle insulin resistance, it may be appreciated that most disorders previously reported in obesity can now be explained by high hypothalamic neuropeptide Y levels. Leptin, produced and secreted by adipose tissue, is a potent anorectic agent whose main action is exerted within the hypothalamus in which it has been shown to decrease neuropeptide Y, therefore food intake. Leptin secretion is favored, in particular, by insulin as well as by glucocorticoids. When leptin is administered to obese mice of the ob/ob strain (which do not produce nor secrete leptin due to a gene mutation), their food intake, body weight and most metabolic abnormalities are normalized. However, in the majority of genetically obese rodents, as well as in obese humans, circulating levels of leptin are high. This is related to hyperinsulinemia- and hypercorticosteronemia-induced leptin oversecretion, as well as to central leptin receptor dysfunctions preventing normal leptin access to and action within specific brain areas. Under these conditions and to prevent the effects of elevated hypothalamic neuropeptide Y levels, neuropeptide Y antagonists or active leptin agonists must be found. Neuropeptide Y and leptin further underline the existence of functional relationship between the brain (hypothalamus) and the periphery (adipose tissue, muscle). Lack of leptin (mutated leptin gene) or inefficient leptin action (leptin receptor defect) results in increased hypothalamic neuropeptide Y levels. The latter favor hyperinsulinemia and hypercorticism both producing oversecretion of leptin which, when inefficient, cannot decrease neuropeptide Y: a vicious circle is created which maintains either a "thrifty phenotype" favoring fat depot or overt obesity, depending on the degree of hyperphagia.
    Annales d Endocrinologie 02/1997; 58(2):137-42. · 1.02 Impact Factor
  • F Rohner-Jeanrenaud, B Jeanrenaud
    European Journal of Endocrinology 01/1997; 135(6):649-50. · 3.14 Impact Factor
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    ABSTRACT: Over the years, the work of research laboratories in Baton Rouge (USA), Seattle (USA) and Geneva (Switzerland) have reached analogous conclusions regarding the main etiology of obesity as studied in animals: it largely lies within the brain, notably within the hypothalamus. The hypothalamus is indeed known to modulate food intake and energy partitioning, while the periphery has also been proposed to feed-back on the central nervous system (CNS) to provide information on the state of body energy stores, the two together constituting a loop system connecting the brain to the periphery (1,2,3). This etiologic viewpoint of a pivotal role of the hypothalamus in obesity syndromes has been strengthened by the discovery of one hypothalamic neuropeptide and one peripheral (adipose tissue) hormone, respectively neuropeptide Y (4), and quite particularly, leptin (5). As neuropeptide Y produces hyperphagia (6, 7) and as leptin produces hypophagia in normal animals (8,9,10), the loop system just mentioned was thought to comprise functional relationships, at least between these two factors. Other evidence also suggested that such a loop system was altered in obese animals.
    Hormone and Metabolic Research 01/1997; 28(12):642-8. · 2.15 Impact Factor
  • Experimental and Clinical Endocrinology & Diabetes - EXP CLIN ENDOCRINOL DIABETES. 01/1997; 105:35-36.

Publication Stats

5k Citations
1,158.54 Total Impact Points

Institutions

  • 1967–2008
    • University of Geneva
      • • Faculty of Medicine
      • • Department of Rehabilitation and Geriatrics
      • • Department of Biochemistry
      Genève, Geneva, Switzerland
  • 2002
    • Sahlgrenska University Hospital
      Goeteborg, Västra Götaland, Sweden
  • 1999
    • Orion Pharma
      Esbo, Southern Finland Province, Finland
  • 1992–1997
    • University of Padova
      • Department of Medicine DIMED
      Padova, Veneto, Italy
  • 1991
    • Université de Neuchâtel
      Neuenburg, Neuchâtel, Switzerland
  • 1983
    • University of Bristol
      • School of Biochemistry
      Bristol, ENG, United Kingdom
    • Purdue University
      West Lafayette, Indiana, United States
  • 1959–1961
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States