| Authors |
Simeone CA, Wilkerson JL, Poss AM, Banks JA, Varre JV, Guevara JL, Hernandez EJ,
Gorsi B, Atkinson DL, Turapov T, Frodsham SG, Morales JCF, O'Neil K, Moore B,
Yandell M, Summers SA, Krolewski AS, Holland WL, Pezzolesi MG
|
| Submitted By |
Marcus Pezzolesi on 10/16/2023 |
| Status |
Published |
| Journal |
NPJ genomic medicine |
| Year |
2022 |
| Date Published |
7/1/2022 |
| Volume : Pages |
7 : 43 |
| PubMed Reference |
35869090 |
| Abstract |
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.
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