RT Journal Article
T1 Mistranslation Drives Alterations in Protein Levels and the Effects of a Synonymous Variant at the Fibroblast Growth Factor 21 Locus.
A1 Bayoumi, Ali
A1 Elsayed, Asmaa
A1 Han, Shuanglin
A1 Petta, Salvatore
A1 Adams, Leon A
A1 Aller, Rocio
A1 Khan, Anis
A1 García-Monzón, Carmelo
A1 Arias-Loste, María Teresa
A1 Miele, Luca
A1 Latchoumanin, Olivier
A1 Alenizi, Shafi
A1 Gallego-Durán, Rocio
A1 Fischer, Janett
A1 Berg, Thomas
A1 Craxì, Antonio
A1 Metwally, Mayada
A1 Qiao, Liang
A1 Liddle, Christopher
A1 Yki-Järvinen, Hannele
A1 Bugianesi, Elisabetta
A1 Romero-Gomez, Manuel
A1 George, Jacob
A1 Eslam, Mohammed
K1 fibroblast growth factor 21
K1 genetics
K1 metabolic
K1 metabolic associated fatty liver disease
AB Fibroblast growth factor 21 (FGF21) is a liver-derived hormone with pleiotropic beneficial effects on metabolism. Paradoxically, FGF21 levels are elevated in metabolic diseases. Interventions that restore metabolic homeostasis reduce FGF21. Whether abnormalities in FGF21 secretion or resistance in peripheral tissues is the initiating factor in altering FGF21 levels and function in humans is unknown. A genetic approach is used to help resolve this paradox. The authors demonstrate that the primary event in dysmetabolic phenotypes is the elevation of FGF21 secretion. The latter is regulated by translational reprogramming in a genotype- and context-dependent manner. To relate the findings to tissues outcomes, the minor (A) allele of rs838133 is shown to be associated with increased hepatic inflammation in patients with metabolic associated fatty liver disease. The results here highlight a dominant role for translation of the FGF21 protein to explain variations in blood levels that is at least partially inherited. These results provide a framework for translational reprogramming of FGF21 to treat metabolic diseases.
YR 2021
FD 2021-05-01
LK http://hdl.handle.net/10668/18013
UL http://hdl.handle.net/10668/18013
LA en
DS RISalud
RD Apr 7, 2025