A role for melanin-concentrating hormone in the central regulation of feeding behaviour

Qu, Daqing; Ludwig, David S.; Gammeltoft, Steen; Piper, Megan; Pelleymounter, Mary Ann; Cullen, Mary Jane; Mathes, Wendy Foulds; Przypek, Jeanne; Kanarek, Robin B.; Maratos–Flier, Eleftheria

doi:10.1038/380243a0

Cited by 1,232 publications

(511 citation statements)

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“…121 One of the unique features of both sets of neurons is that they provide monosynaptic projections to a variety of CNS sites including the cerebral cortex, amygdala, and the spinal cord. [118][119][120][121] Similarly, a broad distribution of the receptors that bind these peptides has also been reported. [122][123][124][125] MCH stimulates feeding behavior when administered centrally.…”

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confidence: 86%

“…66 As noted, the LHA has long been considered to play an essential role in regulating food intake. Recently, two orexigenic peptides produced by discrete populations of LHA neurons in rodents and humans refocused attention on the LHA: melanin-concentrating hormone (MCH) [118][119][120] and the orexins (ORX, also called hypocretins). 121 One of the unique features of both sets of neurons is that they provide monosynaptic projections to a variety of CNS sites including the cerebral cortex, amygdala, and the spinal cord.…”

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confidence: 99%

“…[122][123][124][125] MCH stimulates feeding behavior when administered centrally. 119 Levels of MCH mRNA are increased during fasting when leptin levels rapidly fall. Importantly, mice lacking MCH are hypophagic and lean despite lowered levels of POMC mRNA and leptin, 120 whereas mice overexpressing MCH are obese and hyperleptinemic.…”

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confidence: 99%

“…133 Finally, as noted, the distribution of MCH-and ORXpositive terminals is widespread not only in subcortical regions but also in cortical regions. [118][119][120][121]133 This unique hypothalamo-cortical innervation pattern implicates both peptides in regulating complex cognitive function. This concept is worth noting when attempting to link sites regulating body weight homeostasis and those involved in several psychiatric disorders.…”

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confidence: 99%

“…199 Acetylcholine has also been indicated to influence MCH signaling; for example, a cholinergic agonist carbachol increases MCH mRNA expression in hypothalamic slices. 200 MCH is, as stressed, an established regulator of energy balance [118][119][120]126,127 and is produced at the LHA that receives leptin and melanocortinergic signals. 66,71,72 Notably, a subset of MCH neurons coexpresses the M3 muscarinic acetylcholine receptor (M3Ach-R), and M3Ach-R À/À mice are hypophagic despite extremely low levels of serum leptin.…”

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confidence: 99%

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Body weight is regulated by the brain: a link between feeding and emotion

2005

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Regulated energy homeostasis is fundamental for maintaining life. Unfortunately, this critical process is affected in a high number of mentally ill patients. Eating disorders such as anorexia nervosa are prevalent in modern societies. Impaired appetite and weight loss are common in patients with depression. In addition, the use of neuroleptics frequently produces obesity and diabetes mellitus. However, the neural mechanisms underlying the pathophysiology of these behavioral and metabolic conditions are largely unknown. In this review, we first concentrate on the established brain machinery of food intake and body weight, especially on the melanocortin and neuropeptide Y (NPY) systems as illustration. These systems play a critical role in receiving and processing critical peripheral metabolic cues such as leptin and ghrelin. It is also notable that both systems modulate emotion and motivated behavior as well. Secondly, we discuss the significance and potential promise of multidisciplinary molecular and neuroanatomic techniques that will likely increase the understanding of brain circuitries coordinating energy homeostasis and emotion. Finally, we introduce several lines of evidence suggesting a link between the melanocortin/NPY systems and several neurotransmitter systems on which many of the psychotropic agents exert their influence. Maintaining energy homeostasis is fundamental for survival. However, obesity due to over-nutrition is an increasing worldwide public health problem. 1 In psychiatric practice, on the other hand, impaired appetite is one of the crucial issues. Anorexia and weight loss are common, for example, in patients suffering from depression. Eating disorders are medically intractable and life threatening. In addition, the so-called 'atypical' antipsychotic agents, currently and widely used to treat psychoses, often induce hyperphagia, obesity, and diabetes mellitus. [2][3][4] In the past decade, fortunately, there has been remarkable progress in understanding the molecular mechanisms of food intake and body weight. This is due in large part to increased research activity towards combating the rising incidences of obesity and associated metabolic disorders. As a result, it is now established that the central nervous system (CNS) senses and processes peripheral metabolic cues including leptin 5 and ghrelin, 6,7 resulting in coordinated energy homeostasis. However, the pathophysiology of the disequilibrium between energy intake and expenditure in psychiatric disorders remains largely unknown. Nevertheless, evidence suggests that several CNS systems regulating energy balance may be dysregulated in patients with mental illnesses, for example, eating disorders, and drug addiction. [8][9][10][11][12][13][14] In the current review, we will illustrate the neuroanatomic and molecular genetic aspects of the melanocortin and neuropeptide Y (NPY) systems residing in the CNS downstream of leptin and ghrelin, to discuss the neural bases of feeding, metabolism, and emotion. Additionally, we point the reader to...

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