Pro-Opiomelanocortin and Melanocortin Receptor 3 and 4 Mutations in Genetic Obesity

YANIK T., Durhan S. T.

Biomolecules, cilt.15, sa.2, 2025 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Derleme
  • Cilt numarası: 15 Sayı: 2
  • Basım Tarihi: 2025
  • Doi Numarası: 10.3390/biom15020209
  • Dergi Adı: Biomolecules
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, Food Science & Technology Abstracts, MEDLINE, Veterinary Science Database, Directory of Open Access Journals
  • Anahtar Kelimeler: genetic obesity, melanocortin receptors, pro-opiomelanocortin
  • Orta Doğu Teknik Üniversitesi Adresli: Evet

Özet

Genetic obesity results from loss-of-function mutations, including those affecting the leptin–melanocortin system, which regulates body weight. Pro-opiomelanocortin (POMC)-derived neurohormones act as ligands for melanocortin receptors (MCRs), regulating the leptin–melanocortin pathway through protein–protein interactions. Loss-of-function mutations in the genes encoding POMC, MC3R, and MC4R can lead to the dysregulation of energy expenditure and feeding balance, early-onset obesity, and developmental dysregulation. Recent studies have identified new genetic regulatory mechanisms and potential biomarker regions for the POMC gene and MC4R secondary messenger pathway associated with obesity. Recent advances in crystal structure studies have enhanced our understanding of the protein interactions in this pathway. This narrative review focuses on recent developments in two key areas related to POMC regulation and the leptin–melanocortin pathway: (1) genetic variations in and functions of POMC, and (2) MC3R and MC4R variants that lead to genetic obesity in humans. Understanding these novel mutations in POMC and MC4R/MC3R, as well as their structural and intracellular mechanisms, may help identify strategies for the treatment and diagnosis of obesity, particularly childhood obesity.