Faculty Opinions recommendation of Role of dorsomedial hypothalamic neuropeptide Y in modulating food intake and energy balance.

CCK and leptin are anorectic hormones produced in the small intestine and white adipose tissue, respectively. Investigating how these hormones act together as an integrated anorectic signal is important for elucidating the mechanisms by which energy balance is maintained. We found here that coadministration of subthreshold CCK and leptin, which individually have no effect on feeding, dramatically reduced food intake in rats. Phosphorylation of AMP-activated protein kinase (AMPK) in the hypothalamus significantly decreased after coinjection of CCK and leptin. In addition, coadministration of these hormones significantly increased mRNA levels of anorectic cocaine- and amphetamine-regulated transcript (CART) and thyrotropin-releasing hormone (TRH) in the hypothalamus. The interactive effect of CCK and leptin on food intake was abolished by intracerebroventricular preadministration of the AMPK activator AICAR or anti-CART/anti-TRH antibodies. These findings indicate that coinjection of CCK and leptin reduces food intake via reduced AMPK phosphorylation and increased CART/TRH in the hypothalamus. Furthermore, by using midbrain-transected rats, we investigated the role of the neural pathway from the hindbrain to the hypothalamus in the interaction of CCK and leptin to reduce food intake. Food intake reduction induced by coinjection of CCK and leptin was blocked in midbrain-transected rats. Therefore, the neural pathway from hindbrain to hypothalamus plays an important role in transmitting the anorectic signals provided by coinjection of CCK and leptin. Our findings give further insight into the mechanisms of feeding and energy balance.

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The role of RFamide peptides in feeding

Journal of Endocrinology ◽

10.1677/joe-06-0069 ◽

2007 ◽

Vol 192 (1) ◽

pp. 3-15 ◽

Cited By ~ 81

Author(s):

David A Bechtold ◽

Simon M Luckman

Keyword(s):

Biological Activity ◽

Energy Balance ◽

Food Intake ◽

Energy Expenditure ◽

Feeding Behaviour ◽

Animal Kingdom ◽

Primary Function

In the three decades since FMRFamide was isolated from the clam Macrocallista nimbosa, the list of RFamide peptides has been steadily growing. These peptides occur widely across the animal kingdom, including five groups of RFamide peptides identified in mammals. Although there is tremendous diversity in structure and biological activity in the RFamides, the involvement of these peptides in the regulation of energy balance and feeding behaviour appears consistently through evolution. Even so, questions remain as to whether feeding-related actions represent a primary function of the RFamides, especially within mammals. However, as we will discuss here, the study of RFamide function is rapidly expanding and with it so is our understanding of how these peptides can influence food intake directly as well as related aspects of feeding behaviour and energy expenditure.

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A potent neuropeptide Y antagonist, 1229U91, suppressed spontaneous food intake in Zucker fatty rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1998.274.5.r1500 ◽

1998 ◽

Vol 274 (5) ◽

pp. R1500-R1504 ◽

Cited By ~ 3

Author(s):

A. Ishihara ◽

T. Tanaka ◽

A. Kanatani ◽

T. Fukami ◽

M. Ihara ◽

...

Keyword(s):

Food Intake ◽

Neuropeptide Y ◽

Feeding Behavior ◽

Physiological Role ◽

Abnormal Behavior ◽

Zucker Rats ◽

Intracerebroventricular Administration ◽

Feeding Suppression ◽

Npy Antagonist

Neuropeptide Y (NPY) is one of the most potent orexigenic substances known. 1229U91 was found to be a potent and selective NPY antagonist. To elucidate a physiological role of NPY in hyperphagia in obese animals, we studied the effect of 1229U91 on spontaneous food intake in obese and lean Zucker rats. The food intake of Zucker rats was suppressed by intracerebroventricular administration of 1229U91 more potently in obese than in lean animals without abnormal behavior (31.7 and 67.3% inhibition at doses of 10 and 30 μg, respectively, in Zucker fatty rats and 22.2% inhibition at 30 μg in lean rats). This compound markedly suppressed NPY-induced food intake at 30 μg but did not affect galanin-induced food intake, suggesting that the feeding suppression seen in Zucker fatty and lean rats is pharmacologically and behaviorally specific. These results suggest that NPY is involved in feeding behavior in Zucker fatty rats and that NPY contributes to feeding to a greater degree in Zucker fatty than in lean rats. The hyperphagia in Zucker fatty rats may be due to the abnormal overactivation of the NPYergic system.

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Effect of neuropeptide Y on ingestive behaviors in the rat

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1987.252.3.r599 ◽

1987 ◽

Vol 252 (3) ◽

pp. R599-R609 ◽

Cited By ~ 15

Author(s):

J. E. Morley ◽

A. S. Levine ◽

B. A. Gosnell ◽

J. Kneip ◽

M. Grace

Keyword(s):

Food Intake ◽

Neuropeptide Y ◽

Home Environment ◽

Active Sites ◽

High Protein Diet ◽

Glucose Levels ◽

Food And Water Intake ◽

Access To Food ◽

Ingestive Behaviors

Neuropeptide Y (NPY) is a potent stimulator of food and water intake in rats. NPY still increases food intake even after a 2-h delay in access to food after central injection. When two injections of NPY are given 2 h apart, the second injection produced a substantial increase in food intake. This suggests that tolerance to the NPY effect does not develop after a single injection of NPY. NPY increases moving and exploration in the absence of food when rats are in their home environment but not when tested in a novel environment. Following administration of NPY, rats preferred a high-carbohydrate diet over a high-fat or high-protein diet. Microinjections of NPY showed that active sites included the anterior ventromedial nucleus, paraventricular nucleus of the hypothalamus, and the posterior lateral hypothalamus. NPY was neither additive nor synergistic when coadministered with norepinephrine. Whereas norepinephrine-induced feeding was inhibited by adrenalectomy and vagotomy, these maneuvers had no effect on NPY-induced food intake. This provides further evidence that NPY does not exert its effects on food intake through an alpha-adrenergic mechanism. The effects of NPY on food intake were attenuated by peripherally administered bombesin and centrally administered corticotropin-releasing factor and calcitonin. Cholecystokinin failed to inhibit NPY-induced feeding. NPY did not alter circulating glucose levels. These studies provide further insights into the role of NPY as a stimulator of ingestive behaviors.

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Hypophagic effects of insulin are mediated via NPY1/NPY2 receptors in broiler cockerels

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2018-0470 ◽

2018 ◽

Vol 96 (12) ◽

pp. 1301-1307 ◽

Cited By ~ 2

Author(s):

Shiba Yousefvand ◽

Farshid Hamidi ◽

Morteza Zendehdel ◽

Abbas Parham

Keyword(s):

Blood Glucose ◽

Energy Balance ◽

Food Intake ◽

Control Group ◽

Control Solution ◽

Treatment Groups ◽

Insulin Control ◽

And Control ◽

Npy Receptors

Neuropeptide Y (NPY) plays a mediatory role in cerebral insulin function by maintaining energy balance. The current study was designed to determine the role of insulin in food intake and its interaction with NPY receptors in 8 experiments using broiler cockerels (4 treatment groups per experiment, except for experiment 8). Chicks received control solution or 2.5, 5, or 10 ng of insulin in experiment 1 and control solution or 1.25, 2.5, or 5 μg of receptor antagonists B5063, SF22, or SML0891 in experiments 2, 3, and 4 through intracerebroventricular (ICV) injection, respectively. In experiments 5, 6, and 7, chicks received ICV injection of B5063, SF22, SML0891, or co-injection of an antagonist + insulin, control solution, and insulin. In experiment 8, blood glucose was measured. Insulin, B5063, and SML0891 decreased food intake, while SF22 led to an increase in food intake. The hypophagic effect of insulin was also reinforced by injection of B560, but ICV injection of SF22 destroyed this hypophagic effect of insulin and increased food intake (p < 0.05). However, SML0891 had no effect on decreased food intake induced by insulin (p > 0.05). At 30 min postinjection, blood sugar in the control group was higher than that in the insulin group (p < 0.05). Therefore, the NPY1 and NPY2 receptors mediate the hypophagic effect of insulin in broiler cockerels.

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Intense exercise and food restriction cause similar hypothalamic neuropeptide Y increases in rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1993.264.2.e279 ◽

1993 ◽

Vol 264 (2) ◽

pp. E279-E284 ◽

Cited By ~ 18

Author(s):

D. E. Lewis ◽

L. Shellard ◽

D. G. Koeslag ◽

D. E. Boer ◽

H. D. McCarthy ◽

...

Keyword(s):

Food Intake ◽

Neuropeptide Y ◽

Energy Intake ◽

Wheel Running ◽

Large Diameter ◽

Negative Energy ◽

Increase Body Weight ◽

Hypothalamic Region ◽

Daily Energy

Neuropeptide Y (NPY) is a potent central appetite stimulant whose concentrations rise markedly in hypothalamic appetite-regulating regions in food-deprived rats. To determine whether increased energy expenditure also affects hypothalamic NPY, we studied the effects of intense physical exercise in rats (n = 10) running voluntarily on a large-diameter exercise wheel. Running was initiated by restricting food intake but stabilized at an average of 8 km/day when food intake was matched to that in 11 nonexercised, freely fed controls [23.9 +/- 1.9 (SE) g/day vs. 24.7 +/- 1.3 g/day; P > 0.5]. Running expended approximately 40% of daily energy intake, and weight gain was significantly inhibited. A separate group (n = 10) of nonexercised rats was food restricted (approximately 15 g/day) to match the weights of the exercised rats. The rats were killed after 40 days, when both experimental groups weighed 30% less than controls (P < 0.01). Hypothalamic NPY concentrations showed significant (P < 0.01) increases of 30–70% in specific regions (arcuate and dorsomedial nuclei and medial preoptic and lateral hypothalamic areas) in both the running and food-restricted groups, compared with controls. There were no significant differences between the two experimental groups in NPY concentrations in any hypothalamic region. These findings suggest that negative energy balance, whether caused by reduced energy intake or increased expenditure, increases hypothalamic NPYergic activity. As NPY acts on the hypothalamus to increase body weight, these data support the postulated homeostatic role of NPY in maintaining nutritional state.

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Activation of Central Neuropeptide Y Y1 Receptors Potently Stimulates Food Intake in Male Rhesus Monkeys*

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.84.10.5897 ◽

1999 ◽

Vol 84 (10) ◽

pp. 3781-3791

Author(s):

P. J. Larsen ◽

M. Tang-Christensen ◽

C. E. Stidsen ◽

K. Madsen ◽

M. S. Smith ◽

...

Keyword(s):

Food Intake ◽

Neuropeptide Y ◽

Rhesus Macaques ◽

Maximal Effect ◽

Central Administration ◽

Glucose Levels ◽

Blood Glucose Levels ◽

Y1 Receptors ◽

Male Rhesus

Abstract The orexigenic role of central neuropeptide Y (NPY) in nonhuman primates has been questioned. Therefore, we have studied the effect of central NPY on feeding in ad libitum-fed male rhesus macaques. NPY dose-dependently increased food intake, with the maximal effect obtained by 50 μg (960 min food intake ± sem, 104 ± 5 to 188 ± 11 g; vehicle vs. NPY; n = 6). Blood glucose levels were unaffected by intracerebroventricular administration of NPY, but animals receiving either 20 or 50 μg displayed increased plasma levels of insulin and cortisol at few time points. To assess the pharmacological specificity of this response, a novel Y1 antagonist,[ (Ile,Glu,Pro,Daba,Tyr, Arg,Leu,Arg,Tyr-NH2)2 cyclic (2,4′),(2′,4)-diamide] (Y1ANT), was synthesized. Receptor binding experiments demonstrated that Y1ANT preferentially binds to Y1 and Y4 receptors (pKi 10.12 ± 0.06 and 9.11 ± 0.05 nmol/L, respectively). Functional analysis revealed that Y1ANT is a Y1 antagonist and a partial Y4 agonist. Central administration of Y1ANT blocked NPY-induced feeding. In food-deprived monkeys, Y1ANT attenuated the feeding response. However, Y1ANT had no effect on food intake in satiated monkeys. Thus, endogenous NPY is likely to be involved in the regulation of food intake in the nonhuman primate, and this effect is at least partially mediated via Y1-like receptors.

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The role of photoperiod on the expression of hypothalamic genes regulating appetite in Chevrier’s field mouse (Apodemus chevrieri)

Animal Biology ◽

10.1163/15707563-00002460 ◽

2015 ◽

Vol 65 (1) ◽

pp. 45-56 ◽

Cited By ~ 2

Author(s):

Lin Zhang ◽

Fang Yang ◽

Jinhong Cai ◽

Chunmei Huang ◽

Zhengkun Wang ◽

...

Keyword(s):

Food Intake ◽

Neuropeptide Y ◽

Mrna Expression ◽

Physiological Role ◽

Field Mouse ◽

Related Protein ◽

Serum Leptin ◽

Significant Difference ◽

Agouti Related Protein

The hypothalamus and leptin play a key role in the regulation of food intake. The present study investigated the effects of 4 weeks of short- or long-photoperiod on serum leptin levels and food intake in relation to mRNA expression levels of neuropeptide Y, agouti-related protein, pro-opiomelanocortin, and cocaine- and amphetamine-regulated transcript in the hypothalamus of Chevrier’s field mouse (Apodemus chevrieri). There was a significant difference in body fat mass, food intake and neuropeptide Y mRNA expression between the two groups, but serum leptin level, agouti-related protein, pro-opiomelanocortin, and cocaine- and amphetamine-regulated transcript mRNA expression in the hypothalamus were not difference between the two groups. The elevation of neuropeptide Y mRNA regulated neuropeptides in the hypothalamus suggests a physiological role of neuroendocrine factors in food intake during the different photoperiod. We conclude that leptin may be involved in energy balance and body mass regulation.

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