Recent progress in genetics, epigenetics and metagenomics unveils the pathophysiology of human obesity

M Pigeyre, FT Yazdi, Y Kaur, D Meyre - Clinical science, 2016 - portlandpress.com
In high-, middle-and low-income countries, the rising prevalence of obesity is the underlying
cause of numerous health complications and increased mortality. Being a complex and …

[HTML][HTML] The hunger genes: pathways to obesity

AA Van der Klaauw, IS Farooqi - Cell, 2015 - cell.com
The global rise in the prevalence of obesity and associated co-morbidities such as type 2
diabetes, cardiovascular disease, and cancer represents a major public health concern. The …

[HTML][HTML] Polygenic prediction of weight and obesity trajectories from birth to adulthood

AV Khera, M Chaffin, KH Wade, S Zahid, J Brancale… - Cell, 2019 - cell.com
Severe obesity is a rapidly growing global health threat. Although often attributed to
unhealthy lifestyle choices or environmental factors, obesity is known to be heritable and …

[HTML][HTML] Evaluation of a melanocortin-4 receptor (MC4R) agonist (Setmelanotide) in MC4R deficiency

TH Collet, B Dubern, J Mokrosinski, H Connors… - Molecular …, 2017 - Elsevier
Abstract Objective Pro-opiomelanocortin (POMC)-derived peptides act on neurons
expressing the Melanocortin 4 receptor (MC4R) to reduce body weight. Setmelanotide is a …

The melanocortin-4 receptor: physiology, pharmacology, and pathophysiology

YX Tao - Endocrine reviews, 2010 - academic.oup.com
Abstract The melanocortin-4 receptor (MC4R) was cloned in 1993 by degenerate PCR;
however, its function was unknown. Subsequent studies suggest that the MC4R might be …

Structure reveals the activation mechanism of the MC4 receptor to initiate satiation signaling

H Israeli, O Degtjarik, F Fierro, V Chunilal, AK Gill… - Science, 2021 - science.org
Obesity is a global epidemic that causes morbidity and impaired quality of life. The
melanocortin receptor 4 (MC4R) is at the crux of appetite, energy homeostasis, and body …

From monogenic to polygenic obesity: recent advances

A Hinney, CIG Vogel, J Hebebrand - European child & adolescent …, 2010 - Springer
The heritability of obesity and body weight in general is high. A small number of confirmed
monogenic forms of obesity—the respective mutations are sufficient by themselves to cause …

Structures of active melanocortin-4 receptor–Gs-protein complexes with NDP-α-MSH and setmelanotide

NA Heyder, G Kleinau, D Speck, A Schmidt… - Cell Research, 2021 - nature.com
Abstract The melanocortin-4 receptor (MC4R), a hypothalamic master regulator of energy
homeostasis and appetite, is a class A G-protein-coupled receptor and a prime target for the …

The role of polygenic susceptibility to obesity among carriers of pathogenic mutations in MC4R in the UK Biobank population

N Chami, M Preuss, RW Walker, A Moscati… - PLoS …, 2020 - journals.plos.org
Background Melanocortin 4 receptor (MC4R) deficiency, caused by mutations in MC4R, is
the most common cause of monogenic forms of obesity. However, these mutations have …

Prevalence of melanocortin-4 receptor deficiency in Europeans and their age-dependent penetrance in multigenerational pedigrees

F Stutzmann, K Tan, V Vatin, C Dina, B Jouret… - Diabetes, 2008 - Am Diabetes Assoc
OBJECTIVE—Melanocortin-4 receptor (MC4R) deficiency is the most frequent genetic cause
of obesity. However, there is uncertainty regarding the degree of penetrance of this …