Genome-wide association studies have identified adenylyl cyclase type 5 (ADCY5) as
candidate gene for diabetes-related quantitative traits and an increased risk of type 2 diabetes. Mice
with a whole-body deletion of Adcy5 (Adcy5–/–) do not develop obesity, glucose intolerance and
insulin resistance, have improved cardiac function and increased longevity. Here, we investigated
Adcy5 knockout mice (Adcy5–/–) to test the hypothesis that changes in adipose tissue (AT) may
contribute to the reported healthier phenotype. In contrast to previous reports, we found that
deletion of Adcy5 did not confer any physiological or biochemical benefits. However, this unexpected
finding allowed us to investigate the effects of Adcy5 depletion on AT independently of lower body
weight and a metabolically healthier phenotype. Adcy5–/– mice exhibited an increased number
of smaller adipocytes, lower mean adipocyte size and a distinct AT gene expression pattern with
midline 1 (Mid1) as the most significantly downregulated gene compared to control mice. Our
Adcy5–/– model challenges previously described beneficial effects of Adcy5 deficiency and suggests
that targeting Adcy5 does not improve insulin sensitivity and may therefore limit the relevance of
ADCY5 as potential drug target.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:89409 |
| Date | 30 January 2024 |
| Creators | Dommel, Sebastian, Hoffmann, Anne, Berger, Claudia, Kern, Matthias, Klöting, Nora, Kannt, Aimo, Blüher, Matthias |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 4353 |
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