Protein‐coding mutation in Adcy3 increases adiposity and alters emotional behaviors sex‐dependently in rats
Fuente:
Wiley Open Access
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Artículo Open Access |
| Published: |
Wiley
2024
|
| Subjects: | |
| Online Access: | |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1867005028185669633 |
|---|---|
| author | Mackenzie K. Fitzpatrick Alexandria Szalanczy Angela Beeson Anusha Vora Christina Scott Michael Grzybowski Jason Klotz Nataley Der Rong Chen Aron M. Geurts Leah C. Solberg Woods |
| author_facet | Mackenzie K. Fitzpatrick Alexandria Szalanczy Angela Beeson Anusha Vora Christina Scott Michael Grzybowski Jason Klotz Nataley Der Rong Chen Aron M. Geurts Leah C. Solberg Woods Mackenzie K. Fitzpatrick Alexandria Szalanczy Angela Beeson Anusha Vora Christina Scott Michael Grzybowski Jason Klotz Nataley Der Rong Chen Aron M. Geurts Leah C. Solberg Woods |
| collection | Wiley Open Access |
| contents | Protein‐coding mutation in Adcy3 increases adiposity and alters emotional behaviors sex‐dependently in rats Mackenzie K. Fitzpatrick Alexandria Szalanczy Angela Beeson Anusha Vora Christina Scott Michael Grzybowski Jason Klotz Nataley Der Rong Chen Aron M. Geurts Leah C. Solberg Woods Obesity AbstractObjectiveAdenylate cyclase 3 (Adcy3) has been linked to both obesity and major depressive disorder. We identified a protein‐coding variant in the transmembrane (TM) helix of Adcy3 in rats; similar obesity variants have been identified in humans. This study investigates the role of a TM variant in adiposity and behavior.MethodsWe mutated the TM domain of Adcy3 (Adcy3mut/mut) and created a heterozygous knockout (Adcy3+/−) in Wistar Kyoto (WKY) rats. Wild‐type, Adcy3+/−, and Adcy3mut/mut rats were fed a high‐fat diet for 12 weeks. We measured body weight, fat mass, glucose tolerance, food intake, metabolism, emotion‐like behaviors, memory, and downstream proteins.ResultsAdcy3+/− and Adcy3mut/mut rats weighed more than wild‐type rats due to increased fat mass. There were key sex differences: adiposity was driven by increased food intake in males but by decreased energy expenditure in females. Adcy3mut/mut males displayed increased passive coping and decreased memory, whereas Adcy3mut/mut females displayed increased anxiety‐like behavior. Adcy3mut/mut males had decreased hypothalamic cAMP‐response element binding protein (CREB) signaling, with decreased phospho‐AMP‐activated protein kinase (p‐AMPK) signaling in both sexes.ConclusionsThe ADCY3 TM domain plays a role in protein function via p‐AMPK and CREB signaling. Adcy3 may contribute to the relationship between obesity and major depressive disorder, and sex influences the relationships between Adcy3, metabolism, and behavior. 10.1002/oby.24178 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| doi_str_mv | 10.1002/oby.24178 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_oby_24178 |
| institution | Wiley Open Access |
| license_str_mv | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| publishDate | 2024 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Protein‐coding mutation in Adcy3 increases adiposity and alters emotional behaviors sex‐dependently in rats Mackenzie K. Fitzpatrick Alexandria Szalanczy Angela Beeson Anusha Vora Christina Scott Michael Grzybowski Jason Klotz Nataley Der Rong Chen Aron M. Geurts Leah C. Solberg Woods Obesity Protein‐coding mutation in Adcy3 increases adiposity and alters emotional behaviors sex‐dependently in rats Mackenzie K. Fitzpatrick Alexandria Szalanczy Angela Beeson Anusha Vora Christina Scott Michael Grzybowski Jason Klotz Nataley Der Rong Chen Aron M. Geurts Leah C. Solberg Woods Obesity AbstractObjectiveAdenylate cyclase 3 (Adcy3) has been linked to both obesity and major depressive disorder. We identified a protein‐coding variant in the transmembrane (TM) helix of Adcy3 in rats; similar obesity variants have been identified in humans. This study investigates the role of a TM variant in adiposity and behavior.MethodsWe mutated the TM domain of Adcy3 (Adcy3mut/mut) and created a heterozygous knockout (Adcy3+/−) in Wistar Kyoto (WKY) rats. Wild‐type, Adcy3+/−, and Adcy3mut/mut rats were fed a high‐fat diet for 12 weeks. We measured body weight, fat mass, glucose tolerance, food intake, metabolism, emotion‐like behaviors, memory, and downstream proteins.ResultsAdcy3+/− and Adcy3mut/mut rats weighed more than wild‐type rats due to increased fat mass. There were key sex differences: adiposity was driven by increased food intake in males but by decreased energy expenditure in females. Adcy3mut/mut males displayed increased passive coping and decreased memory, whereas Adcy3mut/mut females displayed increased anxiety‐like behavior. Adcy3mut/mut males had decreased hypothalamic cAMP‐response element binding protein (CREB) signaling, with decreased phospho‐AMP‐activated protein kinase (p‐AMPK) signaling in both sexes.ConclusionsThe ADCY3 TM domain plays a role in protein function via p‐AMPK and CREB signaling. Adcy3 may contribute to the relationship between obesity and major depressive disorder, and sex influences the relationships between Adcy3, metabolism, and behavior. 10.1002/oby.24178 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| title | Protein‐coding mutation in Adcy3 increases adiposity and alters emotional behaviors sex‐dependently in rats |
| topic | Obesity |
| url | https://onlinelibrary.wiley.com/doi/10.1002/oby.24178 |