Melanocortin mediated inhibition of feeding behavior in rats

Murphy, Beth Ann; Nunes, Christian N.; Ronan, John; Harper, Claude; Beall, M.J; Hanaway, Michael J.; Fairhurst, Anna‐Marie; Ploeg, Lex H.T. Van der; Maclntyre, D. E.; Mellin, T.N.

doi:10.1016/s0143-4179(98)90077-4

Cited by 102 publications

(64 citation statements)

References 37 publications

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“…A prominent role for the MC 4 R was highlighted by MC 4 R knockout mice, which exhibited maturity-onset obesity, overeating, hyperinsulinemia, and increased linear growth (Huszar et al 1997). The role of the MC 4 R in body weight regulation was further confirmed by pharmacologic studies showing that MC 4 R agonists suppress food intake and antagonists increase food intake (Kask et al 1998a;Murphy et al 1998;Skuladottir et al 1999). These studies led ultimately to the discovery of mutations in the melanocortin system in obese humans (Krude et al 1998).…”

Section: Animal Models Of Obesitymentioning

confidence: 99%

Relevance of animal models to human eating disorders and obesity

2008

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Background and rationale This review addresses the role animal models play in contributing to our knowledge about the eating disorders anorexia nervosa (AN) and bulimia nervosa (BN) and obesity. Objectives Explore the usefulness of animal models in complex biobehavioral familial conditions, such as AN, BN, and obesity, that involve interactions among genetic, physiologic, psychological, and cultural factors. Results and conclusionsThe most promising animal model to mimic AN is the activity-based anorexia rodent model leading to pathological weight loss. The paradigm incorporates reward elements of the drive for activity in the presence of an appetite and allows the use of genetically modified animals. For BN, the sham-feeding preparation in rodents equipped with a gastric fistula appears to be best suited to reproduce the postprandial emesis and the defects in satiety. Animal models that incorporate genes linked to behavior and mood may clarify biobehavioral processes underlying AN and BN. By contrast, a relative abundance of animal models has contributed to our understanding of human obesity. Both environmental and genetic determinants of obesity have been modeled in rodents. Here, we consider single gene mutant obesity models, along with models of obesigenic environmental conditions. The contributions of animal models to obesity research are illustrated by their utility for identifying genes linked to human obesity, for elucidating the pathways that regulate body weight and for the identification of potential therapeutic targets. The utility of these models may be further improved by exploring the impact of experimental manipulations on the behavioral determinants of energy balance.

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Section: Animal Models Of Obesitymentioning

confidence: 99%

Relevance of animal models to human eating disorders and obesity

2008

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“…Feed intake may be regulated primarily by NPY, proopiomelanocortin and AGRP, with leptin being the primary peripheral signal regulating the activity of these peptides. Recent evidence suggests that the melanocortin system, specifically signaling emanating from MC4-R, is a major pathway in regulating feeding behavior (Murphy et al 1998, Cone 1999. In the present study, administration of an MC3/4-R agonist, NDP-…”

Section: Discussionmentioning

confidence: 67%

The role of melanocortin-3 and -4 receptor in regulating appetite, energy homeostasis and neuroendocrine function in the pig

Barb¹,

Robertson²,

Barrett³

et al. 2004

Journal of Endocrinology

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A recently discovered class of receptors, melanocortin-3 and -4 receptor (MC3/4-R), are located within the brain and modulate feed intake in rodents. Stimulation of the receptor (agonist) inhibits feed intake whereas blockade (antagonist) of the receptor increases intake. Our knowledge of factors regulating voluntary feed intake in humans and domestic animals is very limited. i.c.v. administration of an MC3/4-R agonist, NDP-MSH, suppressed (P,0·05) feed intake compared with controls at 12, 24, 48 and 72 h after treatment in growing pigs. Fed pigs were more responsive to the MC3/4-R agonist then fasted animals. However, i.c.v. treatment with MC3/4-R antagonist, SHU9119, failed to stimulate intake. The failure of MC3/4-R antagonist to stimulate feed intake suggests involvement of other brain hormone(s) which antagonize the action of SHU9119 at the MC3/4-R, blocking its stimulatory effect on intake. Treatment with NDP-MSH or SHU9119, across a wide dose range, failed to affect LH and GH secretion, except for the 10 µg dose of NDP-MSH, which exhibited both a stimulatory and an inhibitory effect on GH secretion in fasted animals. Treatment with agouti-related peptide, a natural brain hormone that blocks the MC3/4R, failed to stimulate feed intake. These results do not support the idea that endogenous melanocortin pays a critical role in regulating feed intake and pituitary hormone secretion in the pig. SHU9119 blocked the NDP-MSH-induced increase in cAMP in HEK293 cells expressing the porcine MC4-R sequence without the missense mutation. The EC 50 and IC 50 values were similar to the human MC4-R, confirming that SHU9119 is a pig MC4-R antagonist. However, pigs were heterozygous for an MC4-R gene missense mutation. It is possible that the MC4-R mutation alters function and this may explain the failure to demonstrate MC3/4-R involvement in modulating feeding behavior and LH and GH secretion in the pig.

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“…This possibility was confirmed by findings that ICV administration MTII can reduce or increase eating, respectively [242][243][244]. MTII reduced intake of scheduled glucose meals and of overnight spontaneous pellet intake [245].…”

Section: Pomc Neuronsmentioning

confidence: 68%

Neuroendocrine control of satiation

Asarian¹,

Bächler

2014

Hormone Molecular Biology and Clinical Investigation

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Abstract:Eating is a simple behavior with complex functions. The unconscious neuroendocrine process that stops eating and brings a meal to its end is called satiation. Energy homeostasis is mediated accomplished through the control of meal size via satiation. It involves neural integrations of phasic negative-feedback signals related to ingested food and tonic signals, such as those related to adipose tissue mass. Energy homeostasis is accomplished through adjustments in meal size brought about by changes in these satiation signals. The best understood meal-derived satiation signals arise from gastrointestinal nutrient sensing. Gastrointestinal hormones secreted during the meal, including cholecystokinin, glucagon-like peptide 1, and PYY, mediate most of these. Other physiological signals arise from activation of metabolic-sensing neurons, mainly in the hypothalamus and caudal brainstem. We review both classes of satiation signal and their integration in the brain, including their processing by melanocortin, neuropeptide Y/agouti-related peptide, serotonin, noradrenaline, and oxytocin neurons. Our review is not comprehensive; rather, we discuss only what we consider the best-understood mechanisms of satiation, with a special focus on normally operating physiological mechanisms.

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Melanocortin mediated inhibition of feeding behavior in rats

Cited by 102 publications

References 37 publications

Relevance of animal models to human eating disorders and obesity

Relevance of animal models to human eating disorders and obesity

The role of melanocortin-3 and -4 receptor in regulating appetite, energy homeostasis and neuroendocrine function in the pig

Neuroendocrine control of satiation

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