Abstract
Melanin-concentrating hormone (MCH) is a 19aa cyclic peptide exclusively expressed in the lateral hypothalamic area, which is an area of the brain involved in a large number of physiological functions and vital processes such as nutrient sensing, food intake, sleep-wake arousal, memory formation, and reproduction. However, the role of the lateral hypothalamic area in metabolic regulation stands out as the most relevant function. MCH regulates energy balance and glucose homeostasis by controlling food intake and peripheral lipid metabolism, energy expenditure, locomotor activity and brown adipose tissue thermogenesis. However, the MCH control of energy balance is a complex mechanism that involves the interaction of several neuroendocrine systems. The aim of the present work is to describe the current knowledge of the crosstalk of MCH with different endocrine factors. We also provide our view about the possible use of melanin-concentrating hormone receptor antagonists for the treatment of metabolic complications. In light of the data provided here and based on its actions and function, we believe that the MCH system emerges as an important target for the treatment of obesity and its comorbidities.
Highlights
Both Melanin-concentrating hormone (MCH) and leptin stimulate sexual behavior, and it has been shown that the effect of leptin on luteinizing hormone (LH) release is mediated by MCH [83]
The hypothalamic pituitary adrenal (HPA) axis is a neuroendocrine pathway that is activated by stress and comprised of three endocrine components: (1) the corticotrophinreleasing factor (CRH) that resides within the paraventricular nucleus (PVN), (2) adrenocorticotropic hormone (ACTH) that is released from the anterior pituitary, and (3) cortisol and corticosterone which are the main glucocorticoids secreted by human and rodent adrenal glands, respectively [94]
The most effective and sustainable approach to decrease body weight and to improve glucose metabolism is bariatric surgery; its invasiveness and side effects limits the access of this approach to obese patients in the general population
Summary
Melanin-concentrating hormone (MCH) was first isolated in 1983 in the pituitary of chum salmon (Oncorhynchus keta), and its name comes from the ability of this hormone to control skin pigmentation [1,2,3]. Subsequent studies have determined that MCH is expressed in the lateral hypothalamic area (LHA) and incertohypothalamic area of mammals, two important anatomic areas in the regulation of feeding behavior and energy conservation [4,5,6]. The Pmch gene yields other pro-MCH neuropeptides, such as neuropeptide-glutamic-isoleucine and neuropeptide-glycine-glutamic acid [4,9]. The function of these peptides remains elusive, but they seem to be devoid of metabolic effect [10,11,12]. It is important to note that in pharmacological models, altered feeding behavior is the main cause of the metabolic actions of MCH signaling. MCH neurons are mostly inhibitory and glutamatergic [13,32], a subset was reported to be gamma aminobutyric acid (GABA)-ergic [32,33]
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