Alteration of NPY and Y1 receptor in dorsomedial and ventromedial areas of hypothalamus in anorectic tumor-bearing rats

Chance, William T.; Xiao, Chun; Dayal, Ramesh; Sheriff, Sulaiman

doi:10.1016/j.peptides.2006.10.018

Cited by 25 publications

(23 citation statements)

References 38 publications

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“…But detailed analyses of Y receptor number, distribution, or kinetics are currently unavailable in the critical regions of the PVH and LHA that could implicate these variables in the differences in NPY efficacy of these two regions. Interestingly, however, reports show that some anorexic stimuli alter NPY Y1 receptor expression in the hypothalamus (9,11,67).…”

Section: Discussionmentioning

confidence: 99%

Site-specific attenuation of food intake but not the latency to eat after hypothalamic injections of neuropeptide Y in dehydrated-anorexic rats

Salter‐Venzon

Watts

2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Anorexia that accompanies cellular dehydration in rats (DE-anorexia) offers a relatively simple model for investigating the functional organization of neural mechanisms that can suppress feeding during dehydration. Previous studies strongly suggest that the inputs that drive ingestive behavior control neurons in the paraventricular nucleus of the hypothalamus (PVH) and lateral hypothalamic area (LHA) remain active during DE-anorexia. Here we examine whether these two regions retain their sensitivity to neuropeptide Y (NPY). NPY is an important component in two major feeding-related inputs from the arcuate nucleus and the hindbrain. We found that intake responses to NPY injections in the LHA and PVH were suppressed in DE-anorexia, but the PVH remained less sensitive to the effects of NPY than the LHA in DE-anorexic animals. Indeed the higher dose of NPY (238 pmol) completely overcame shorter periods of DE-anorexia when injected into the LHA but not the PVH. However, the latency to eat after NPY injections remained unchanged from control animals, regardless of NPY dose, injection location, or intensity of anorexia. Furthermore, the onset and size of the strong and rapidly induced compensatory feeding that follows the return of water to DE-anorexic animals was also unaffected by any NPY injections. These data support the hypothesis that DE-anorexia develops as a consequence of the premature termination of regularly initiated meals, which perhaps involves processes that alter the sensitivity of satiety mechanisms downstream to the PVH and LHA.

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Section: Discussionmentioning

confidence: 99%

Site-specific attenuation of food intake but not the latency to eat after hypothalamic injections of neuropeptide Y in dehydrated-anorexic rats

Salter‐Venzon

Watts

2009

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Immuncytochemical studies in tumor-bearing rats with anorexia-cachexia show decreased NPY innervation of hypothalamic nuclei (52), which is reversed by tumor resection (53). Direct measurement of NPY concentrations in the hypothalamus of tumor-bearing rats with anorexia-cachexia reveals a significant decrease of this orexigenic peptide (63) despite the fact that increased mRNA levels for NPY have been also reported (11). Furthermore, mRNA levels and immunostaining of the NPY receptor, the Y1 receptor, are decreased in the hypothalamus of tumor-bearing rats (11), whereas tumor resection restores normal hypothalamic NPY levels (75).…”

Section: The Melanocortin Systemmentioning

confidence: 99%

Neural control of the anorexia-cachexia syndrome

Laviano¹,

Inui²,

Marks³

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

111

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cachexia syndrome is a debilitating clinical condition characterizing the course of chronic diseases, which heavily impacts on patients' morbidity and quality of life, ultimately accelerating death. The pathogenesis is multifactorial and reflects the complexity and redundancy of the mechanisms controlling energy homeostasis under physiological conditions. Accumulating evidence indicates that, during disease, disturbances of the hypothalamic pathways controlling energy homeostasis occur, leading to profound metabolic changes in peripheral tissues. In particular, the hypothalamic melanocortin system does not respond appropriately to peripheral inputs, and its activity is diverted largely toward the promotion of catabolic stimuli (i.e., reduced energy intake, increased energy expenditure, possibly increased muscle proteolysis, and adipose tissue loss). Hypothalamic proinflammatory cytokines and serotonin, among other factors, are key in triggering hypothalamic resistance. These catabolic effects represent the central response to peripheral challenges (i.e., growing tumor, renal, cardiac failure, disrupted hepatic metabolism) that are likely sensed by the brain through the vagus nerve. Also, disease-induced changes in fatty acid oxidation within hypothalamic neurons may contribute to the dysfunction of the hypothalamic melanocortin system. Ultimately, sympathetic outflow mediates, at least in part, the metabolic changes in peripheral tissues. Other factors are likely involved in the pathogenesis of the anorexia-cachexia syndrome, and their role is currently being elucidated. However, available evidence shows that the constellation of symptoms characterizing this syndrome should be considered, at least in part, as different phenotypes of common neurochemical/metabolic alterations in the presence of a chronic inflammatory state. melanocortin; cytokines; serotonin; malonyl-coenzyme A; vagus nerve; sympathetic output THE ANOREXIA-CACHEXIA SYNDROME is a debilitating condition characterizing the clinical journey of patients suffering from chronic diseases including cancer, chronic obstructive pulmonary disease, tuberculosis, chronic heart failure, and end-stage renal insufficiency (64). As an experimental model, it represents a reliable and unique tool for the investigation of the mechanisms regulating energy intake and homeostasis. Beyond its relevance to human physiology, this syndrome impacts on clinical practice since it is highly prevalent and negatively influences patients' morbidity, mortality (66), and quality of life (57).The anorexia-cachexia syndrome is clinically characterized by a number of signs and symptoms interfering with energy intake (i.e., reduced appetite, early satiety, changes in taste/ smell) and affecting nutritional status (i.e., increased metabolic rate, weight loss, hormonal alterations, muscle and adipose tissue wasting, functional impairment, fatigue). At the biochemical and molecular levels, the main features of the anorexia-cachexia syndrome are the profound alterations of brain neurochemis...

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“…Although not universally observed in other models of cancer anorexia (17), MCA sarcoma-bearing rats exhibited less feeding than controls following the injection of AgRP into the 3rd ventricle. Our more recent observations suggest that both mRNA and immunostaining for NPY Y-1 receptor is reduced in the hypothalamus of anorectic TB rats (43). Therefore, the dysfunction of NPY feeding mechanisms in TB rats may be associated with reduced NPY receptor availability.…”

Section: Discussionmentioning

confidence: 82%

Continuous Intravenous Infusion of Ghrelin Does Not Stimulate Feeding in Tumor-Bearing Rats

Chance

Dayal

Friend

et al. 2007

Nutrition and Cancer

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The development of anorexia continues to be a serious treatment issue for cancer patients. Because the orexigenic peptide, ghrelin, is active through systemic routes and activates hypothalamic neuropeptide systems known to be refractory in anorectic tumor-bearing (TB) rats, we investigated whether it would prevent the development of cancer anorexia when infused continuously intravenously. The 24-h food intake was increased in nontumor-bearing (NTB) rats at a dose of 288 microg/day ghrelin. However, no tested dose of ghrelin, up to 576 microg/day, elicited increased feeding in TB rats prior to or subsequent to the development of anorexia. In hypothalamus, ghrelin-infused TB rats exhibited significantly increased concentration of neuropeptide Y (NPY) as compared to saline-infused TB rats. Hypothalamic expression of NPY and agouti-related protein (AgRP) messenger RNA were elevated in ghrelin-infused TB rats as compared to NTB rats, but saline-infused TB rats also exhibited increased expression of AgRP. Proopiomelanocortin message was reduced in ghrelin-infused and saline-infused TB rats as compared to noninfused TB control rats. Although ghrelin infusion did not preserve muscle protein, a significant saving in body fat was observed in TB rats. Thus, the adiposity effects of ghrelin did not require an orexigenic response to the peptide. These results suggest that continuous ghrelin infusion may not be an effective treatment for cancer anorexia.

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Alteration of NPY and Y1 receptor in dorsomedial and ventromedial areas of hypothalamus in anorectic tumor-bearing rats

Cited by 25 publications

References 38 publications

Site-specific attenuation of food intake but not the latency to eat after hypothalamic injections of neuropeptide Y in dehydrated-anorexic rats

Site-specific attenuation of food intake but not the latency to eat after hypothalamic injections of neuropeptide Y in dehydrated-anorexic rats

Neural control of the anorexia-cachexia syndrome

Continuous Intravenous Infusion of Ghrelin Does Not Stimulate Feeding in Tumor-Bearing Rats

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