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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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Autores principales: Szalanczy, Alexandria M., Goff, Emily, Seshie, Osborne, Deal, Aaron, Grzybowski, Michael, Klotz, Jason, Chuang Key, Chia-Chi, Geurts, Aron M., Solberg Woods, Leah C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9535360/
https://www.ncbi.nlm.nih.gov/pubmed/36212147
http://dx.doi.org/10.3389/fgene.2022.942574
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author Szalanczy, Alexandria M.
Goff, Emily
Seshie, Osborne
Deal, Aaron
Grzybowski, Michael
Klotz, Jason
Chuang Key, Chia-Chi
Geurts, Aron M.
Solberg Woods, Leah C.
author_facet Szalanczy, Alexandria M.
Goff, Emily
Seshie, Osborne
Deal, Aaron
Grzybowski, Michael
Klotz, Jason
Chuang Key, Chia-Chi
Geurts, Aron M.
Solberg Woods, Leah C.
author_sort Szalanczy, Alexandria M.
collection PubMed
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.
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spelling pubmed-95353602022-10-07 Keratinocyte-associated protein 3 plays a role in body weight and adiposity with differential effects in males and females Szalanczy, Alexandria M. Goff, Emily Seshie, Osborne Deal, Aaron Grzybowski, Michael Klotz, Jason Chuang Key, Chia-Chi Geurts, Aron M. Solberg Woods, Leah C. Front Genet Genetics 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. Frontiers Media S.A. 2022-09-21 /pmc/articles/PMC9535360/ /pubmed/36212147 http://dx.doi.org/10.3389/fgene.2022.942574 Text en Copyright © 2022 Szalanczy, Goff, Seshie, Deal, Grzybowski, Klotz, Chuang Key, Geurts and Solberg Woods. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Szalanczy, Alexandria M.
Goff, Emily
Seshie, Osborne
Deal, Aaron
Grzybowski, Michael
Klotz, Jason
Chuang Key, Chia-Chi
Geurts, Aron M.
Solberg Woods, Leah C.
Keratinocyte-associated protein 3 plays a role in body weight and adiposity with differential effects in males and females
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 Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9535360/
https://www.ncbi.nlm.nih.gov/pubmed/36212147
http://dx.doi.org/10.3389/fgene.2022.942574
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