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Dommel, S.* ; Hoffmann, A. ; Berger, C.* ; Kern, M. ; Klöting, N. ; Kannt, A.* ; Blüher, M.

Effects of whole-body adenylyl cyclase 5 (Adcy5) deficiency on systemic insulin sensitivity and adipose tissue.

Int. J. Mol. Sci. 22:4353 (2021)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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 con-tribute 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 find-ing 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 mid-line 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. –/– –/– –/– –/–
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Adcy5 Knockout ; Adipocyte Size ; Gene Expression ; Insulin Resistance ; Metabolism ; Running Activity; Diet-induced Obesity; Calorie Restriction; Skeletal-muscle; Life-span; Mice; Protects; Disruption; Receptor; Type-5; Homeostasis
Sprache englisch
Veröffentlichungsjahr 2021
HGF-Berichtsjahr 2021
ISSN (print) / ISBN 1661-6596
e-ISSN 1422-0067
Quellenangaben Band: 22, Heft: 9, Seiten: , Artikelnummer: 4353 Supplement: ,
Verlag MDPI
Verlagsort Basel
Begutachtungsstatus Peer reviewed
Institut(e) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
POF Topic(s) 30201 - Metabolic Health
Forschungsfeld(er) Helmholtz Diabetes Center
PSP-Element(e) G-506501-001
G-506500-001
Förderungen
Deutsche Forschungsgemeinschaft (DFG, German Research foundation)
Scopus ID 85104391306
PubMed ID 33919448
Erfassungsdatum 2021-04-30