Obesity-Associated GNAS Mutations and the Melanocortin Pathway.
Edson Mendes de OliveiraJulia M KeoghFleur TalbotElana HenningRachel AhmedAliki PerdikariRebecca BoundsNatalia WasilukVikram AyinampudiInês BarrosoJacek MokrosińskiDeepthi JyothishSharon LimSanjay GuptaMelanie KershawCristina MateiPraveen ParthaTabitha RandellAntoinette McAulayLouise C WilsonTim CheethamElizabeth C CrownePeter ClaytonDavid R FitzPatrickPublished in: The New England journal of medicine (2021)
Because pathogenic mutations may manifest with obesity alone, screening of children with severe obesity for GNAS deficiency may allow early diagnosis, improving clinical outcomes, and melanocortin agonists may aid in weight loss. GNAS mutations that are identified by means of unbiased genetic testing differentially affect GPCR signaling pathways that contribute to clinical heterogeneity. Monogenic diseases are clinically more variable than their classic descriptions suggest. (Funded by Wellcome and others.).
Keyphrases
- weight loss
- insulin resistance
- metabolic syndrome
- bariatric surgery
- high fat diet induced
- type diabetes
- roux en y gastric bypass
- weight gain
- gastric bypass
- signaling pathway
- glycemic control
- early onset
- adipose tissue
- single cell
- pi k akt
- cell proliferation
- oxidative stress
- induced apoptosis
- endoplasmic reticulum stress