A dominant negative ADIPOQ mutation in a diabetic family with renal disease, hypoadiponectinemia, and hyperceramidemia.
Journal
NPJ genomic medicine
ISSN: 2056-7944
Titre abrégé: NPJ Genom Med
Pays: England
ID NLM: 101685193
Informations de publication
Date de publication:
22 Jul 2022
22 Jul 2022
Historique:
received:
11
11
2021
accepted:
06
07
2022
entrez:
22
7
2022
pubmed:
23
7
2022
medline:
23
7
2022
Statut:
epublish
Résumé
Adiponectin, encoded by ADIPOQ, is an insulin-sensitizing, anti-inflammatory, and renoprotective adipokine that activates receptors with intrinsic ceramidase activity. We identified a family harboring a 10-nucleotide deletion mutation in ADIPOQ that cosegregates with diabetes and end-stage renal disease. This mutation introduces a frameshift in exon 3, resulting in a premature termination codon that disrupts translation of adiponectin's globular domain. Subjects with the mutation had dramatically reduced circulating adiponectin and increased long-chain ceramides levels. Functional studies suggest that the mutated protein acts as a dominant negative through its interaction with non-mutated adiponectin, decreasing circulating adiponectin levels, and correlating with metabolic disease.
Identifiants
pubmed: 35869090
doi: 10.1038/s41525-022-00314-z
pii: 10.1038/s41525-022-00314-z
pmc: PMC9307825
doi:
Types de publication
Journal Article
Langues
eng
Pagination
43Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK115824
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002538
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK036836
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK131609
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK130296
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK128641
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK112826
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK122001
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK091317
Pays : United States
Informations de copyright
© 2022. The Author(s).
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