Keratinocyte-associated protein 3 plays a role in body weight and adiposity with differential effects in males and females
Despite the obesity crisis in the United States, the underlying genetics are poorly understood. Our lab previously identified Keratinocyte-associated protein 3, Krtcap3, as a candidate gene for adiposity through a genome-wide association study in outbred rats, where increased liver expression of Krt...
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| Format: | Article |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.942574/full |
| _version_ | 1798000615300792320 |
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| author | Alexandria M. Szalanczy Emily Goff Osborne Seshie Aaron Deal Michael Grzybowski Jason Klotz Chia-Chi Chuang Key Aron M. Geurts Leah C. Solberg Woods |
| author_facet | Alexandria M. Szalanczy Emily Goff Osborne Seshie Aaron Deal Michael Grzybowski Jason Klotz Chia-Chi Chuang Key Aron M. Geurts Leah C. Solberg Woods |
| author_sort | Alexandria M. Szalanczy |
| collection | DOAJ |
| description | Despite the obesity crisis in the United States, the underlying genetics are poorly understood. Our lab previously identified Keratinocyte-associated protein 3, Krtcap3, as a candidate gene for adiposity through a genome-wide association study in outbred rats, where increased liver expression of Krtcap3 correlated with decreased fat mass. Here we seek to confirm that Krtcap3 expression affects adiposity traits. To do so, we developed an in vivo whole-body Krtcap3 knock-out (KO) rat model. Wild-type (WT) and KO rats were placed onto a high-fat (HFD) or low-fat diet (LFD) at 6 weeks of age and were maintained on diet for 13 weeks, followed by assessments of metabolic health. We hypothesized that Krtcap3-KO rats will have increased adiposity and a worsened metabolic phenotype relative to WT. We found that KO male and female rats have significantly increased body weight versus WT, with the largest effect in females on a HFD. KO females also ate more and had greater adiposity, but were more insulin sensitive than WT regardless of diet condition. Although KO males weighed more than WT under both diet conditions, there were no differences in eating behavior or fat mass. Interestingly, KO males on a HFD were more insulin resistant than WT. This study confirms that Krtcap3 plays a role in body weight regulation and demonstrates genotype- and sex-specific effects on food intake, adiposity, and insulin sensitivity. Future studies will seek to better understand these sex differences, the role of diet, and establish a mechanism for Krtcap3 in obesity. |
| first_indexed | 2024-04-11T11:23:10Z |
| format | Article |
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| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-11T11:23:10Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-da510ac2eda8434b98ad770e82d351b32022-12-22T04:26:38ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-09-011310.3389/fgene.2022.942574942574Keratinocyte-associated protein 3 plays a role in body weight and adiposity with differential effects in males and femalesAlexandria M. Szalanczy0Emily Goff1Osborne Seshie2Aaron Deal3Michael Grzybowski4Jason Klotz5Chia-Chi Chuang Key6Aron M. Geurts7Leah C. Solberg Woods8Department 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, Medical College of Wisconsin, Milwaukee, WI, United StatesDepartment of Physiology, Medical College of Wisconsin, Milwaukee, WI, 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 Internal Medicine, School of Medicine, Wake Forest University, Winston Salem, NC, United StatesDespite the obesity crisis in the United States, the underlying genetics are poorly understood. Our lab previously identified Keratinocyte-associated protein 3, Krtcap3, as a candidate gene for adiposity through a genome-wide association study in outbred rats, where increased liver expression of Krtcap3 correlated with decreased fat mass. Here we seek to confirm that Krtcap3 expression affects adiposity traits. To do so, we developed an in vivo whole-body Krtcap3 knock-out (KO) rat model. Wild-type (WT) and KO rats were placed onto a high-fat (HFD) or low-fat diet (LFD) at 6 weeks of age and were maintained on diet for 13 weeks, followed by assessments of metabolic health. We hypothesized that Krtcap3-KO rats will have increased adiposity and a worsened metabolic phenotype relative to WT. We found that KO male and female rats have significantly increased body weight versus WT, with the largest effect in females on a HFD. KO females also ate more and had greater adiposity, but were more insulin sensitive than WT regardless of diet condition. Although KO males weighed more than WT under both diet conditions, there were no differences in eating behavior or fat mass. Interestingly, KO males on a HFD were more insulin resistant than WT. This study confirms that Krtcap3 plays a role in body weight regulation and demonstrates genotype- and sex-specific effects on food intake, adiposity, and insulin sensitivity. Future studies will seek to better understand these sex differences, the role of diet, and establish a mechanism for Krtcap3 in obesity.https://www.frontiersin.org/articles/10.3389/fgene.2022.942574/fullobesitygeneticsrat modelfat masssex differences |
| spellingShingle | Alexandria M. Szalanczy Emily Goff Osborne Seshie Aaron Deal Michael Grzybowski Jason Klotz Chia-Chi Chuang Key Aron M. Geurts Leah C. Solberg Woods Keratinocyte-associated protein 3 plays a role in body weight and adiposity with differential effects in males and females Frontiers in Genetics obesity genetics rat model fat mass sex differences |
| title | Keratinocyte-associated protein 3 plays a role in body weight and adiposity with differential effects in males and females |
| title_full | Keratinocyte-associated protein 3 plays a role in body weight and adiposity with differential effects in males and females |
| title_fullStr | Keratinocyte-associated protein 3 plays a role in body weight and adiposity with differential effects in males and females |
| title_full_unstemmed | Keratinocyte-associated protein 3 plays a role in body weight and adiposity with differential effects in males and females |
| title_short | Keratinocyte-associated protein 3 plays a role in body weight and adiposity with differential effects in males and females |
| title_sort | keratinocyte associated protein 3 plays a role in body weight and adiposity with differential effects in males and females |
| topic | obesity genetics rat model fat mass sex differences |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.942574/full |
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