Melanocortin-4 Receptor Signalling: Importance for Weight Regulation and Obesity Treatment

被引：127

作者：

Kuehnen, Peter ^{[1
,2
,3
,4
]}

Krude, Heiko ^{[1
,2
,3
,4
]}

Biebermann, Heike ^{[1
,2
,3
,4
]}

机构：

[1] Charite Univ Med Berlin, Inst Expt Pediat Endocrinol, Augustenburger Pl 1, D-13353 Berlin, Germany

[2] Free Univ Berlin, Augustenburger Pl 1, D-13353 Berlin, Germany

[3] Humboldt Univ, Augustenburger Pl 1, D-13353 Berlin, Germany

[4] Berlin Inst Hlth, Augustenburger Pl 1, D-13353 Berlin, Germany

来源：

TRENDS IN MOLECULAR MEDICINE | 2019年 / 25卷 / 02期

关键词：

Y GASTRIC BYPASS; INTRACELLULAR FREE CALCIUM; BARIATRIC SURGERY; FRAMESHIFT MUTATION; SLEEVE GASTRECTOMY; METABOLIC-RATE; MC4R AGONIST; GENE; PREVALENCE; ACTIVATION;

D O I：

10.1016/j.molmed.2018.12.002

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The melanocortin-4 receptor (MC4R) - embedded in the leptin-melanocortin pathway - is activated by proopiomelanocortin (POMC)-derived neuropeptides such as alpha- and beta-melanocyte-stimulating hormone (MSH) and plays an important role in hypothalamic body-weight regulation. Accordingly, MC4R is a potential drug target to combat obesity. Previous attempts to develop MC4R agonists failed due to ineffectiveness or severe adverse events. Recently, a new generation of MC4R ligands was developed. Specifically, setmelanotide was found to be effective by inducing biased signalling of the MC4R and thereby reducing feelings of hunger and leading to substantial weight loss in patients with POMC or leptin receptor deficiency. This new potential pharmacological treatment option could be beneficial for further groups of obese patients with defects in the leptin-melanocortin signalling pathway.

引用

页码：136 / 148

页数：13

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