Hypothalamic neuropeptide Y disturbances in the obese (cp/cp) JCR:LA corpulent rat

Williams, Gareth; Shellard, Lyndsey; Lewis, Diane E.; McKibbin, P.E.; McCarthy, H. D.; Koeslag, Dorothy G.; Russell, James C.

doi:10.1016/0196-9781(92)90085-h

Cited by 53 publications

(21 citation statements)

References 17 publications

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“…In support of this hypothesis, elevated levels of NPY and/or its transcript have been observed in the hypothalami of genetically obese rodents such as fa/fa and cp/cp rats [6,7] as well as ob/ob and db/db mice [8]. This increase has been detected early after weaning in faJfa rats, corresponding with the time when their obesity syndrome first becomes apparent [6].…”

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confidence: 72%

Chronic central neuropeptide Y infusion in normal rats: status of the hypothalamo-pituitary-adrenal axis, and vagal mediation of hyperinsulinaemia

et al. 1997

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Summary 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 importantJJregulators 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.

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confidence: 72%

Chronic central neuropeptide Y infusion in normal rats: status of the hypothalamo-pituitary-adrenal axis, and vagal mediation of hyperinsulinaemia

et al. 1997

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“…States of obesity, diabetes and hypercortisolemia, are also associated with abnormal glucose homeostasis, and, consequently, increased NPY (208,231). What remains to be demonstrated is that this increase in NPY, a marker of disturbed glucose homeostasis, actually contributes in a significant fashion to the associated hyperphagia, lipogenesis and body weight gain (203,(262)(263)(264)(271)(272)(273)(274)). a greater inhibition of feeding and weight gain through its receptors in the brain (1, 14).…”

Section: Adrenal Steroids and Their Receptors In Relation To Normal Bmentioning

confidence: 99%

Adrenal Steroid Receptors: Interactions with Brain Neuropeptide Systems in Relation to Nutrient Intake and Metabolism

Tempel

Leibowitz

1994

J Neuroendocrinology

194

127

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The glucocorticoid, corticosterone (CORT), is believed to have an important function in modulating nutrient ingestion and metabolism. Recent evidence described in this review suggests that the effects of this adrenal hormone are mediated through two steroid receptor subtypes, the type I mineralocorticoid receptor and the type II glucocorticoid receptor. These receptors, which have different affinities for CORT, respond to different levels of circulating hormone. They mediate distinct effects of the steroid, which can be distinguished by the specific nutrient ingested and by the particular period of the circadian cycle.Under normal physiological conditions, the type I receptor is tonically activated, either by low basal levels of circulating CORT (0.5-2 pg%) normally available across the circadian cycle or possibly by the mineralocorticoid aldosterone. This type I activation is required for the maintenance of fat ingestion and fat deposition that occurs during most meals of the feeding cycle. In contrast, the type II receptor is phasically activated by moderate levels of CORT (2-1 0 pg%) normally reached during the circadian peak. Activation of this receptor is required for the natural surge in carbohydrate ingestion and metabolism that is essential at the onset of the active feeding cycle when the body's glycogen stores are at their nadir, and gluconeogenesis is needed to maintain blood glucose levels. This receptor is also activated during periods of increased energy requirements, such as, after exercise and food restriction, when CORT levels rise further ( > 10 pg%) and when its catabolic effects on fat and protein stores predominate to provide additional substrates for glucose homeostasis. These functions of CORT on fat and carbohydrate balance are mediated, in part, by type I and type II receptors located within the hypothalamic paraventricular nucleus, which is known to have key functions in controlling nutrient intake and metabolism, as well as circulating CORT levels. Moreover, the type II receptors within this nucleus, in addition to the arcuate nucleus, may interact positively with the peptide, neuropeptide Y, and the catecholamine, norepinephrine, both of which act to enhance natural carbohydrate feeding and CORT release at the onset of the natural feeding cycle.Thus, under normal conditions, endogenous CORT has a primary function in controlling nutrient ingestion and metabolism over the natural circadian cycle, through the coordinated action of the type I and type II steroid receptor systems. Through this action, CORT has impact on total caloric intake and body weight gain over the long term. Moreover, under conditions of obesity, diabetes and food restriction, steroid receptor function is greatly disturbed in association with chronic high circulating levels of CORT and abnormal glucose homeostasis. These disturbances in steroid action, along with dysfunction in brain neurochemical processes, very possibly contribute to the maintenance of hyperphagia and body weight gain in obese and diabetic ...

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“…The arcuate nucleus (ARC) of the hypothalamus undergoes wholesale changes in neuronal activity and neuropeptide expression in response to an energy deficit (202), integrating numerous signals from the periphery as it develops the overall picture of energy depletion. Key aspects of this general response persist after long-term weight reduction from an obese state, including increased expression of ARC neuropeptide Y (NPY) (24,137,168,248,251) and Agouti-related peptide (AgRP) (168, 251), as well as decreased expression of proopiomelanocortin (POMC) (137). Concomitant elevations in the firing of NPY/AgRP neurons and reductions in the firing rate of POMC neurons would be expected with this gene expression profile.…”

Section: Drive To Regain In the Brainmentioning

confidence: 99%

Biology's response to dieting: the impetus for weight regain

MacLean

Bergouignan

Cornier

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

368

326

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Dieting is the most common approach to losing weight for the majority of obese and overweight individuals. Restricting intake leads to weight loss in the short term, but, by itself, dieting has a relatively poor success rate for long-term weight reduction. Most obese people eventually regain the weight they have worked so hard to lose. Weight regain has emerged as one of the most significant obstacles for obesity therapeutics, undoubtedly perpetuating the epidemic of excess weight that now affects more than 60% of U.S. adults. In this review, we summarize the evidence of biology's role in the problem of weight regain. Biology's impact is first placed in context with other pressures known to affect body weight. Then, the biological adaptations to an energy-restricted, low-fat diet that are known to occur in the overweight and obese are reviewed, and an integrative picture of energy homeostasis after long-term weight reduction and during weight regain is presented. Finally, a novel model is proposed to explain the persistence of the "energy depletion" signal during the dynamic metabolic state of weight regain, when traditional adiposity signals no longer reflect stored energy in the periphery. The preponderance of evidence would suggest that the biological response to weight loss involves comprehensive, persistent, and redundant adaptations in energy homeostasis and that these adaptations underlie the high recidivism rate in obesity therapeutics. To be successful in the long term, our strategies for preventing weight regain may need to be just as comprehensive, persistent, and redundant, as the biological adaptations they are attempting to counter. energy restriction; diet-induced obesity; obesity prone; weight loss; energy balance IN THE UNITED STATES, OVER 60% of adults and close to 20% of children are overweight or obese (35,174). A number of effective weight loss strategies are available, but most are only transiently effective over a period of 3 to 6 mo. Less than 20% of individuals that have attempted to lose weight are able to achieve and maintain a 10% reduction over a year (128). Over one-third of lost weight tends to return within the first year, and the majority is gained back within 3 to 5 years (3,246). A number of reasons have been proposed for the high incidence of weight regain (69,246), and several point to the biological response to weight loss.The objective of this review is to examine the role of this biological response in the process of weight regain. Biological regulation is first discussed in relation to other nonbiological pressures that affect body weight as weight is gained, lost, and regained. The specific biological adaptations to the most common form of dieting, an energy-restricted low-fat diet, are then discussed in more detail. Previous reviews provide extensive descriptions of the normal adaptive response to energy restriction. We do not attempt to recapitulate those efforts here. Rather, the unique perspective of this review summarizes those adaptations that have been confirmed o...

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Hypothalamic neuropeptide Y disturbances in the obese (cp/cp) JCR:LA corpulent rat

Cited by 53 publications

References 17 publications

Chronic central neuropeptide Y infusion in normal rats: status of the hypothalamo-pituitary-adrenal axis, and vagal mediation of hyperinsulinaemia

Chronic central neuropeptide Y infusion in normal rats: status of the hypothalamo-pituitary-adrenal axis, and vagal mediation of hyperinsulinaemia

Adrenal Steroid Receptors: Interactions with Brain Neuropeptide Systems in Relation to Nutrient Intake and Metabolism

Biology's response to dieting: the impetus for weight regain

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