Understanding melanocortin-4 receptor control of neuronal circuits: Toward novel therapeutics for obesity syndrome

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It is well known that melanocortin-4 receptors (MC4Rs) and central melanocortin pathways regulate food intake, energy expenditure, and glucose homeostasis. Importantly, MC4R deficiency is the most common monogenic cause of human obesity. Interestingly, MC4Rs expressed by distinct central nuclei are responsible for the different physiological function of MC4R stimulation. In addition, MC4Rs activate multiple intracellular and/or synaptic signaling molecules for the regulation of neuronal circuits. Therefore, MC4Rs and the downstream signal molecules are plausible targets for development of novel therapeutics against obesity and obesity-related metabolic disorders. In this review, we discuss recent findings on the neuronal circuits and signaling molecules that are responsible for MC4R control energy balance and autonomic function. Further, we review status of MC4R agonists as novel therapeutics for obesity syndrome. We believe that comprehensive understanding of signaling molecules involved in MC4R control of neuronal circuits will help to design MC4R agonists as safe and effective anti-obesity drugs.
Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
Issue Date
2018-03
Language
English
Article Type
Review
Keywords

AGOUTI-RELATED PROTEIN; IMMORTALIZED HYPOTHALAMIC NEURONS; INTRACELLULAR FREE CALCIUM; MITOGEN-ACTIVATED PROTEIN; MSH ANALOGS; IN-VITRO; PARAVENTRICULAR NUCLEUS; FUNCTIONAL SELECTIVITY; ENERGY-EXPENDITURE; PENILE ERECTION

Citation

PHARMACOLOGICAL RESEARCH, v.129, pp.10 - 19

ISSN
1043-6618
DOI
10.1016/j.phrs.2018.01.004
URI
http://hdl.handle.net/10203/240929
Appears in Collection
BS-Journal Papers(저널논문)
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