Melanocortin pathways: suppressed and stimulated melanocortin-4 receptor (MC4R)

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11120%2F20%3A43920727" target="_blank" >RIV/00216208:11120/20:43920727 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00023761:_____/20:N0000026

Výsledek na webu

<a href="https://doi.org/10.33549/physiolres.934512" target="_blank" >https://doi.org/10.33549/physiolres.934512</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.33549/physiolres.934512" target="_blank" >10.33549/physiolres.934512</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Melanocortin pathways: suppressed and stimulated melanocortin-4 receptor (MC4R)

Popis výsledku v původním jazyce

Leptin-melanocortin pathway plays an essential role in the body weight regulation. Enhanced melanocortin signaling in the hypothalamus results in both decreased food intake and increased energy expenditure. The discovery of monogenic obesities with dysfunction of melanocortin-4 receptor (MC4R) greatly contributed to understanding of energy balance regulation. This review presents phenotypical characterization and prevalence of the MC4R gene mutations. Genome-wide association studies revealed that MC4R gene is significantly related not only to monogenic obesities but also to common obesity. An interaction of variants in the MC4R gene with fat mass and obesity associated (FTO) gene significantly increases the risk for obesity, particularly in adolescence. On the other hand, about 15 % of the MC4R gene variants result in a gain of function that protects against obesity and is associated with favorable metabolic profile. Long-term attempts to activate the MC4R have recently been finalized by a discovery of setmelanotide, a novel specific MC4R agonist that is devoid of untoward cardiovascular side-effects. The employment of specific MC4R agonists may open new horizons not only in the treatment of rare monogenic obesities but also in some common obesities where stimulation of MC4R could be achieved.

Název v anglickém jazyce

Melanocortin pathways: suppressed and stimulated melanocortin-4 receptor (MC4R)

Popis výsledku anglicky

Leptin-melanocortin pathway plays an essential role in the body weight regulation. Enhanced melanocortin signaling in the hypothalamus results in both decreased food intake and increased energy expenditure. The discovery of monogenic obesities with dysfunction of melanocortin-4 receptor (MC4R) greatly contributed to understanding of energy balance regulation. This review presents phenotypical characterization and prevalence of the MC4R gene mutations. Genome-wide association studies revealed that MC4R gene is significantly related not only to monogenic obesities but also to common obesity. An interaction of variants in the MC4R gene with fat mass and obesity associated (FTO) gene significantly increases the risk for obesity, particularly in adolescence. On the other hand, about 15 % of the MC4R gene variants result in a gain of function that protects against obesity and is associated with favorable metabolic profile. Long-term attempts to activate the MC4R have recently been finalized by a discovery of setmelanotide, a novel specific MC4R agonist that is devoid of untoward cardiovascular side-effects. The employment of specific MC4R agonists may open new horizons not only in the treatment of rare monogenic obesities but also in some common obesities where stimulation of MC4R could be achieved.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30202 - Endocrinology and metabolism (including diabetes, hormones)

Projekt

—

Návaznosti

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Physiological Research

ISSN

0862-8408

e-ISSN

—

Svazek periodika

69

Číslo periodika v rámci svazku

Suppl. 2

Stát vydavatele periodika

CZ - Česká republika

Počet stran výsledku

10

Strana od-do

"S245"-"S254"

Kód UT WoS článku

000581646000009

EID výsledku v databázi Scopus

2-s2.0-85094570401