Chronic stress from adolescence to adulthood increases adiposity and anxiety in rats with decreased expression of Krtcap3
We previously identified Keratinocyte-associated protein 3, Krtcap3, as a novel adiposity gene, but subsequently found that its impact on adiposity may depend on environmental stress. To more thoroughly understand the connection between Krtcap3, adiposity, and stress, we exposed wild-type (WT) and K...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2024-01-01
|
| Series: | Frontiers in Genetics |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1247232/full |
| _version_ | 1797348621459390464 |
|---|---|
| author | Alexandria M. Szalanczy Mackenzie Fitzpatrick Angela Beeson Trangdai Bui Christina Dyson Seth Eller Julia Landry Christina Scott Michael Grzybowski Jason Klotz Aron M. Geurts Jeff L. Weiner Eva E. Redei Leah C. Solberg Woods |
| author_facet | Alexandria M. Szalanczy Mackenzie Fitzpatrick Angela Beeson Trangdai Bui Christina Dyson Seth Eller Julia Landry Christina Scott Michael Grzybowski Jason Klotz Aron M. Geurts Jeff L. Weiner Eva E. Redei Leah C. Solberg Woods |
| author_sort | Alexandria M. Szalanczy |
| collection | DOAJ |
| description | We previously identified Keratinocyte-associated protein 3, Krtcap3, as a novel adiposity gene, but subsequently found that its impact on adiposity may depend on environmental stress. To more thoroughly understand the connection between Krtcap3, adiposity, and stress, we exposed wild-type (WT) and Krtcap3 knock-out (KO) rats to chronic stress then measured adiposity and behavioral outcomes. We found that KO rats displayed lower basal stress than WT rats under control conditions and exhibited metabolic and behavioral responses to chronic stress exposure. Specifically, stress-exposed KO rats gained more weight, consumed more food when socially isolated, and displayed more anxiety-like behaviors relative to control KO rats. Meanwhile, there were minimal differences between control and stressed WT rats. At study conclusion stress-exposed KO rats had increased corticosterone (CORT) relative to control KO rats with no differences between WT rats. In addition, KO rats, independent of prior stress exposure, had an increased CORT response to removal of their cage-mate (psychosocial stress), which was only seen in WT rats when exposed to chronic stress. Finally, we found differences in expression of the glucocorticoid receptor, Nr3c1, in the pituitary and colon between control and stress-exposed KO rats that were not present in WT rats. These data support that Krtcap3 expression affects stress response, potentially via interactions with Nr3c1, with downstream effects on adiposity and behavior. Future work is necessary to more thoroughly understand the role of Krtcap3 in the stress response. |
| first_indexed | 2024-03-08T12:09:16Z |
| format | Article |
| id | doaj.art-ff93cd10e3234dcbb7a2173ff0636eba |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-03-08T12:09:16Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-ff93cd10e3234dcbb7a2173ff0636eba2024-01-23T04:17:04ZengFrontiers Media S.A.Frontiers in Genetics1664-80212024-01-011410.3389/fgene.2023.12472321247232Chronic stress from adolescence to adulthood increases adiposity and anxiety in rats with decreased expression of Krtcap3Alexandria M. Szalanczy0Mackenzie Fitzpatrick1Angela Beeson2Trangdai Bui3Christina Dyson4Seth Eller5Julia Landry6Christina Scott7Michael Grzybowski8Jason Klotz9Aron M. Geurts10Jeff L. Weiner11Eva E. Redei12Leah C. Solberg Woods13Department of Internal Medicine, School of Medicine, Wake Forest University, Winston Salem, NC, United StatesDepartment of Internal Medicine, School of Medicine, Wake Forest University, Winston Salem, NC, United StatesDepartment of Internal Medicine, School of Medicine, Wake Forest University, Winston Salem, NC, United StatesDepartment of Internal Medicine, School of Medicine, Wake Forest University, Winston Salem, NC, United StatesDepartment of Physiology and Pharmacology, School of Medicine, Wake Forest University, Winston Salem, NC, United StatesDepartment of Internal Medicine, School of Medicine, Wake Forest University, Winston Salem, NC, United StatesDepartment of Internal Medicine, School of Medicine, Wake Forest University, Winston Salem, NC, United StatesDepartment of Internal Medicine, School of Medicine, Wake Forest University, Winston Salem, NC, United StatesDepartment of Physiology, Medical College of Wisconsin, Milwaukee, WI, United StatesDepartment of Physiology, Medical College of Wisconsin, Milwaukee, WI, United StatesDepartment of Physiology, Medical College of Wisconsin, Milwaukee, WI, United StatesDepartment of Physiology and Pharmacology, School of Medicine, Wake Forest University, Winston Salem, NC, United StatesDepartment of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United StatesDepartment of Internal Medicine, School of Medicine, Wake Forest University, Winston Salem, NC, United StatesWe previously identified Keratinocyte-associated protein 3, Krtcap3, as a novel adiposity gene, but subsequently found that its impact on adiposity may depend on environmental stress. To more thoroughly understand the connection between Krtcap3, adiposity, and stress, we exposed wild-type (WT) and Krtcap3 knock-out (KO) rats to chronic stress then measured adiposity and behavioral outcomes. We found that KO rats displayed lower basal stress than WT rats under control conditions and exhibited metabolic and behavioral responses to chronic stress exposure. Specifically, stress-exposed KO rats gained more weight, consumed more food when socially isolated, and displayed more anxiety-like behaviors relative to control KO rats. Meanwhile, there were minimal differences between control and stressed WT rats. At study conclusion stress-exposed KO rats had increased corticosterone (CORT) relative to control KO rats with no differences between WT rats. In addition, KO rats, independent of prior stress exposure, had an increased CORT response to removal of their cage-mate (psychosocial stress), which was only seen in WT rats when exposed to chronic stress. Finally, we found differences in expression of the glucocorticoid receptor, Nr3c1, in the pituitary and colon between control and stress-exposed KO rats that were not present in WT rats. These data support that Krtcap3 expression affects stress response, potentially via interactions with Nr3c1, with downstream effects on adiposity and behavior. Future work is necessary to more thoroughly understand the role of Krtcap3 in the stress response.https://www.frontiersin.org/articles/10.3389/fgene.2023.1247232/fullobesitystressHPA axisgeneticsbehavioranxiety |
| spellingShingle | Alexandria M. Szalanczy Mackenzie Fitzpatrick Angela Beeson Trangdai Bui Christina Dyson Seth Eller Julia Landry Christina Scott Michael Grzybowski Jason Klotz Aron M. Geurts Jeff L. Weiner Eva E. Redei Leah C. Solberg Woods Chronic stress from adolescence to adulthood increases adiposity and anxiety in rats with decreased expression of Krtcap3 Frontiers in Genetics obesity stress HPA axis genetics behavior anxiety |
| title | Chronic stress from adolescence to adulthood increases adiposity and anxiety in rats with decreased expression of Krtcap3 |
| title_full | Chronic stress from adolescence to adulthood increases adiposity and anxiety in rats with decreased expression of Krtcap3 |
| title_fullStr | Chronic stress from adolescence to adulthood increases adiposity and anxiety in rats with decreased expression of Krtcap3 |
| title_full_unstemmed | Chronic stress from adolescence to adulthood increases adiposity and anxiety in rats with decreased expression of Krtcap3 |
| title_short | Chronic stress from adolescence to adulthood increases adiposity and anxiety in rats with decreased expression of Krtcap3 |
| title_sort | chronic stress from adolescence to adulthood increases adiposity and anxiety in rats with decreased expression of krtcap3 |
| topic | obesity stress HPA axis genetics behavior anxiety |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1247232/full |
| work_keys_str_mv | AT alexandriamszalanczy chronicstressfromadolescencetoadulthoodincreasesadiposityandanxietyinratswithdecreasedexpressionofkrtcap3 AT mackenziefitzpatrick chronicstressfromadolescencetoadulthoodincreasesadiposityandanxietyinratswithdecreasedexpressionofkrtcap3 AT angelabeeson chronicstressfromadolescencetoadulthoodincreasesadiposityandanxietyinratswithdecreasedexpressionofkrtcap3 AT trangdaibui chronicstressfromadolescencetoadulthoodincreasesadiposityandanxietyinratswithdecreasedexpressionofkrtcap3 AT christinadyson chronicstressfromadolescencetoadulthoodincreasesadiposityandanxietyinratswithdecreasedexpressionofkrtcap3 AT setheller chronicstressfromadolescencetoadulthoodincreasesadiposityandanxietyinratswithdecreasedexpressionofkrtcap3 AT julialandry chronicstressfromadolescencetoadulthoodincreasesadiposityandanxietyinratswithdecreasedexpressionofkrtcap3 AT christinascott chronicstressfromadolescencetoadulthoodincreasesadiposityandanxietyinratswithdecreasedexpressionofkrtcap3 AT michaelgrzybowski chronicstressfromadolescencetoadulthoodincreasesadiposityandanxietyinratswithdecreasedexpressionofkrtcap3 AT jasonklotz chronicstressfromadolescencetoadulthoodincreasesadiposityandanxietyinratswithdecreasedexpressionofkrtcap3 AT aronmgeurts chronicstressfromadolescencetoadulthoodincreasesadiposityandanxietyinratswithdecreasedexpressionofkrtcap3 AT jefflweiner chronicstressfromadolescencetoadulthoodincreasesadiposityandanxietyinratswithdecreasedexpressionofkrtcap3 AT evaeredei chronicstressfromadolescencetoadulthoodincreasesadiposityandanxietyinratswithdecreasedexpressionofkrtcap3 AT leahcsolbergwoods chronicstressfromadolescencetoadulthoodincreasesadiposityandanxietyinratswithdecreasedexpressionofkrtcap3 |