Neurochemical phenotype of hypothalamic neurons  showing Fos expression 23 h after intracranial AgRP

Zheng, Huiyuan; Corkern, Michele; Crousillac, Scott; Patterson, Laurel M.; Phifer, Curtis B.; Berthoud, Hans‐Rudolf

doi:10.1152/ajpregu.00019.2002

Cited by 69 publications

(41 citation statements)

References 71 publications

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“…The observation that the pattern of fos expression differs between the acute and longer-term responses to intracerebroventricular AgRP was proposed as evidence that the short-term and long-term responses to AgRP have different mechanisms (22). It could also be evidence of the activation of neural circuits to counteract the long-term effects of AgRP as suggested by Berthoud and colleagues (57). The underlying mechanism(s) responsible for the prolonged responses to changes in melanocortin receptor modulation remain unclear.…”

Section: Discussionmentioning

confidence: 99%

Melanocortin activity in the amygdala controls appetite for dietary fat

Boghossian

Park

York

2010

American Journal of Physiology-Regulatory, Integrative and Comp

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The amygdala is rich in melanocortin 4 receptors. Because the reduction in dietary fat intake after enterostatin is injected in the central nucleus of the amygdala (CeA) is blocked by a melanocortin 4 receptor antagonist, we investigated the role of melanocortin activity in the CeA in regulating food intake and macronutrient choice. Sprague-Dawley rats, fitted with CeA cannulas, were fed either chow, a high-fat (HF) diet, or adapted to a two-choice HF or low-fat (LF) diet. Injections of the MC4R agonist melanotan II (MTII) in the CeA had a dose-dependent inhibitory effect on food intake that lasted for at least 24 h. This response was greater in rats fed a HF diet. The inverse agonist agouti-related protein (AgRP) and antagonist SHU-9119 increased food intake in a dose-dependent manner, with the hyperphagia lasting for 60 h. In rats adapted to a two-choice HF/LF diet, MTII decreased HF consumption but had no effect on LF consumption, resulting in a long-lasting decrease in total calorie intake (Ϫ35.5% after 24 h, P Ͻ 0.05). Total calorie intake increased in both AgRP-and SHU-9119-treated rats (32 and 109% after 24 h, respectively) as the result of increased intake of HF diet. There was no modification of LF consumption with AgRP treatment and a transient nonsignificant decrease with SHU-9119 treatment. Amygdala brain-derived neurotrophic factor expression was increased by AgRP in fed rats. These results identify the amygdala as a site of action for the melanocortin system to control food intake and dietary preferences.agouti-related protein; melanotan II; SHU-9119; brain derived neurotrophic factor, food intake FOR YEARS, HYPOTHALAMIC CENTERS have been considered as the major brain centers regulating food intake and/or macronutrient selection (45). The neural circuits involved in the regulation of feeding behavior are complex, and more recent studies implicate other parts of the brain in the regulation of ingestive behaviors. Areas such as the nucleus accumbens, the amygdala, the brain stem, and many others form together with the hypothalamic areas a complex circuitry regulating all levels of feeding behavior (6,8,55). Indeed, the paraventricular nucleus (PVN) is not essential for either neuropeptide Y (NPY)-induced feeding or the anorexic response to melanocortin activity (16) since both are evident in PVN-lesioned rats. Furthermore, the anorectic response to melanotan II (MTII) is evident in the dorsovagal complex of the brain stem (52,58).A number of neuropeptides and compounds are known to selectively affect macronutrient intake when administered centrally. For example, the orexigenic NPY (47, 48, 50) , norepinephrine (30, 50), or agouti-related protein (AgRP) (23) have been reported to induce specific selection of macronutrients. Enterostatin, a satiety factor secreted in the gastrointestinal tract and expressed also in the central nervous system, induces an immediate reduction in food intake and inhibits appetite specifically for dietary fat when injected peripherally or centrally (31,37,39).It has been hy...

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Section: Discussionmentioning

confidence: 99%

Melanocortin activity in the amygdala controls appetite for dietary fat

Boghossian

Park

York

2010

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Although NPY mRNA levels are reduced 6 h after refeeding, AgRP levels remain elevated (Swart et al 2002). This prolonged response results in a greater cumulative effect on food intake than NPY, and probably involves more diverse signalling pathways than the melanocortin pathway alone (Hagan et al 2000, Zheng et al 2002.…”

Section: Hypothalamic Neuropeptidesmentioning

confidence: 99%

Appetite control

Wynne¹,

Stanley²,

McGowan³

et al. 2005

Journal of Endocrinology

475

403

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Our understanding of the physiological systems that regulate food intake and body weight has increased immensely over the past decade. Brain centres, including the hypothalamus, brainstem and reward centres, signal via neuropeptides which regulate energy homeostasis. Insulin and hormones synthesized by adipose tissue reflect the long-term nutritional status of the body and are able to influence these circuits. Circulating gut hormones modulate these pathways acutely and result in appetite stimulation or satiety effects. This review discusses central neuronal networks and peripheral signals which contribute energy homeostasis, and how a loss of the homeostatic process may result in obesity. It also considers future therapeutic targets for the treatment of obesity.

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“…AgRP acts as an antagonist at melanocortin-4 receptors and causes profound and prolonged hyperphagia; under some conditions the hyperphagia may be apparent for as long as 7 days after intracerebroventricular administration (15,38,50). Pharmacological characterization of the human agouti signaling peptide showed that, as expected, it behaves as a competitive antagonist of ␣-MSH and melanocortin receptors (48).…”

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confidence: 82%

“…The latter nucleus tends to be a site where feedinginhibitory inputs are processed (45,50). Thus urocortin and CRH injected into the paraventricular nucleus reduced feeding induced by food deprivation or by NPY (45).…”

mentioning

confidence: 99%

“…Thus simultaneous administration of the opioid antagonist naloxone blocks AgRP-induced hyperphagia, whereas naloxone given 24 h after AgRP does not block the established hyperphagia (15). Zheng et al (50) used double labeling to map neurons that were activated 1 day after intracerebroventricular AgRP. In the lateral hypothalamus, orexin neurons, but not those expressing CART or melanin-concentrating hormone, showed increased c-Fos immunoreactivity; in the arcuate nucleus, CART, but not NPY, neurons showed increased c-Fos labeling.…”

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confidence: 99%

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Peptides that regulate food intake

Cupples

2003

American Journal of Physiology-Regulatory, Integrative and Comp

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IN THIS ISSUE OF THE JOURNAL are published the first group of papers submitted to the Special Call for Papers on the subject "Peptides that Regulate Food Intake." These nine papers (7a, 32a, 37a, 37b, 41a, 42a, 43a, 46a, 49a) illustrate both the breadth and depth of the subject. They continue the contribution made by papers published in the American Journal of Physiology-Regulatory, Integrative and Comparative Physiology toward understanding of the regulation of food intake and body weight. What are these peptides? How do they act? How do they interact among themselves and with other control systems? These are all important questions addressed by recent publications in this journal and highlighted below.Leptin is secreted by adipocytes and signals fat content to neurons in the arcuate nucleus of the hypothalamus. Leptin inhibits release of the potent orexigens neuropeptide Y (NPY) and agouti-related peptide (AgRP), which are coexpressed in neurons of the arcuate nucleus of the hypothalamus. Leptin also increases release, from adjacent neurons, of anorexigens ␣-melanocyte stimulating hormone (␣-MSH) and cocaine-and amphetamine-regulated transcript (CART), which are also coexpressed (38). Food deprivation increases NPY and AgRP mRNA and decreases that of proopiomelanocortin (POMC) in the arcuate nucleus. These changes are largely reversed 6 h after refeeding (43), but not by leptin infusion or a palatable, noncaloric mash, indicating the importance of other postabsorptive factors (43). Zhang et al. (49) showed in several different fat depots of mice that leptin mRNA content varied directly with adipocyte volume, whereas messages for tumor necrosis factor-␣, insulin receptor, and glucocorticoid receptor were all independent of cell volume. Obesity induced by feeding rodents a high-fat or high-energy diet is associated with leptin resistance; leptin becomes less effective at reducing food intake. The leptin resistance caused by changing from chow to a high-fat diet occurred rapidly and was apparent before any change of body composition could take place (26), suggesting that dietary fat, per se, can induce leptin resistance. Importantly, in rats maintained on chow, leptin sensitivity predicts the development of diet-induced obesity when the animals are subsequently placed on a high-energy diet (24). Rats with the lowest leptin sensitivity become most obese. Changes in circulating leptin can be of varying importance in different models of weight loss. For example, lactating sheep are in negative energy balance despite hyperphagia. Here the reduction of plasma leptin appears to be a primary signal for the hyperphagia (42). In contrast, the weight loss induced by acute stress, although associated with reduced circulating leptin, is unchanged when plasma leptin is clamped high (17). In addition to its effects on food intake, leptin also has significant metabolic actions. With the use of different strains of db/db mice having profound leptin resistance due to absence of the long form of the leptin receptor, it was possi...

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Neurochemical phenotype of hypothalamic neurons showing Fos expression 23 h after intracranial AgRP

Cited by 69 publications

References 71 publications

Melanocortin activity in the amygdala controls appetite for dietary fat

Melanocortin activity in the amygdala controls appetite for dietary fat

Appetite control

Peptides that regulate food intake

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