Effects of Restraint Stress and Spontaneous Hypertension on Neuropeptide Y Neurones in the Brainstem and Arcuate Nucleus

ABSTRACT Agouti-related protein (AgRP), a neuropeptide abundantly expressed in the arcuate nucleus of the hypothalamus, potently stimulates feeding and body weight gain in rodents. AgRP is believed to exert its effects through the blockade of signaling by α-melanocyte-stimulating hormone at central nervous system (CNS) melanocortin-3 receptor (Mc3r) and Mc4r. We generated AgRP-deficient (Agrp−/− ) mice to examine the physiological role of AgRP. Agrp−/− mice are viable and exhibit normal locomotor activity, growth rates, body composition, and food intake. Additionally, Agrp−/− mice display normal responses to starvation, diet-induced obesity, and the administration of exogenous leptin or neuropeptide Y (NPY). In situ hybridization failed to detect altered CNS expression levels for proopiomelanocortin, Mc3r, Mc4r, or NPY mRNAs in Agrp−/− mice. As AgRP and the orexigenic peptide NPY are coexpressed in neurons of the arcuate nucleus, we generated AgRP and NPY double-knockout (Agrp−/− ;Npy−/− ) mice to determine whether NPY or AgRP plays a compensatory role in Agrp−/− or NPY-deficient (Npy−/− ) mice, respectively. Similarly to mice deficient in either AgRP or NPY, Agrp−/− ;Npy−/− mice suffer no obvious feeding or body weight deficits and maintain a normal response to starvation. Our results demonstrate that neither AgRP nor NPY is a critically required orexigenic factor, suggesting that other pathways capable of regulating energy homeostasis can compensate for the loss of both AgRP and NPY.

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Diet-derived nutrients mediate the inhibition of hypothalamic NPY neurons in the arcuate nucleus of mice during refeeding

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.91014.2008 ◽

2009 ◽

Vol 297 (1) ◽

pp. R100-R110 ◽

Cited By ~ 17

Author(s):

Csilla Becskei ◽

Thomas A. Lutz ◽

Thomas Riediger

Keyword(s):

Neuropeptide Y ◽

Arcuate Nucleus ◽

Peptide Yy ◽

Small Reduction ◽

Hypothalamic Arcuate Nucleus ◽

Ad Libitum ◽

Fos Expression

Fasting activates orexigenic neuropeptide Y neurons in the hypothalamic arcuate nucleus (ARC) of mice, which is reversed by 2 h refeeding with standard chow. Here, we investigated the contribution of diet-derived macronutrients and anorectic hormones to the reversal of the fasting-induced ARC activation during 2 h refeeding. Refeeding of 12-h-fasted mice with a cellulose-based, noncaloric mash induced only a small reduction in c-Fos expression. Refeeding with diets, containing carbohydrates, protein, or fat alone reversed it similar to chow; however, this effect depended on the amount of intake. The fasting-induced ARC activation was unchanged by subcutaneously injected amylin, CCK (both 20 μg/kg), insulin (0.2 U/kg and 0.05 U/kg) or leptin (2.6 mg/kg). Insulin and leptin had no effect on c-Fos expression in neuropeptide Y or proopiomelanocortin-containing ARC neurons. Interestingly, CCK but not amylin reduced the ghrelin-induced c-Fos expression in the ARC in ad libitum-fed mice, suggesting that CCK may inhibit orexigenic ARC neurons when acting together with other feeding-related signals. We conclude that all three macronutrients and also non-nutritive, ingestion-dependent signals contribute to an inhibition of orexigenic ARC neurons after refeeding. Similar to the previously demonstrated inhibitory in vivo action of peptide YY, CCK may be a postprandial mediator of ARC inhibition.

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Neuromedin B and Gastrin-Releasing Peptide Excite Arcuate Nucleus Neuropeptide Y Neurons in a Novel Transgenic Mouse Expressing Strong Renilla Green Fluorescent Protein in NPY Neurons

Journal of Neuroscience ◽

10.1523/jneurosci.3249-08.2009 ◽

2009 ◽

Vol 29 (14) ◽

pp. 4622-4639 ◽

Cited By ~ 125

Author(s):

A. N. van den Pol ◽

Y. Yao ◽

L.-Y. Fu ◽

K. Foo ◽

H. Huang ◽

...

Keyword(s):

Green Fluorescent Protein ◽

Neuropeptide Y ◽

Transgenic Mouse ◽

Arcuate Nucleus ◽

Fluorescent Protein ◽

Gastrin Releasing Peptide ◽

Neuromedin B ◽

Green Fluorescent

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Neuropeptide Y (NPY) -induced reductions in alcohol intake during continuous access and following alcohol deprivation are not altered by restraint stress in alcohol-preferring (P) rats

Pharmacology Biochemistry and Behavior ◽

10.1016/j.pbb.2010.10.002 ◽

2011 ◽

Vol 97 (3) ◽

pp. 453-461 ◽

Cited By ~ 13

Author(s):

Megan L. Bertholomey ◽

Angela N. Henderson ◽

Nancy E. Badia-Elder ◽

Robert B. Stewart

Keyword(s):

Neuropeptide Y ◽

Restraint Stress ◽

Alcohol Intake ◽

Continuous Access

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Dexamethasone rapidly increases hypothalamic neuropeptide Y secretion in adrenalectomized ob/ob mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1996.271.1.e151 ◽

1996 ◽

Vol 271 (1) ◽

pp. E151-E158 ◽

Cited By ~ 2

Author(s):

H. L. Chen ◽

D. R. Romsos

Keyword(s):

Neuropeptide Y ◽

Arcuate Nucleus ◽

Rapid Onset ◽

Brown Adipose ◽

Specific Enhancement ◽

Brown Adipose Tissue Thermogenesis ◽

The Central Nervous System ◽

Rapid Transport ◽

The Brain

A single intracerebroventricular injection of dexamethasone (DEX) rapidly (within 30 min) suppresses brown adipose tissue thermogenesis and increases plasma insulin concentrations in adrenal-ectomized (ADX) ob/ob mice but not in ADX lean mice. Intracerebroventricular neuropeptide Y (NPY) administered intracerebroventricularly causes these same metabolic changes within 30 min in both ob/ob and lean ADX mice. We therefore hypothesized that DEX exerts these rapid-onset metabolic actions in ob/ob mice via a phenotype-specific enhancement of NPY secretion within the central nervous system. In support of this hypothesis, DEX (a type II glucocorticoid receptor agonist) administered intracerebroventricularly selectively lowered NPY concentrations in the whole hypothalamus of ADX ob/ob mice by 35% and in the arcuate nucleus region by approximately 70% within 30 min but not in the brain stem or hippocampus or in any of these regions of lean mice. DEX also functioned in vitro to enhance depolarization-dependent release of NPY from hypothalamic blocks of ADX ob/ob mice but not of ADX lean mice. Thus DEX acts in the hypothalamus of ob/ob mice in a phenotype-specific manner to evoke rapid transport of NPY from cell bodies within the arcuate nucleus to terminal regions including the dorsomedial and ventromedial hypothalamic regions for release.

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