Alterations in Adipose Tissue and Adipokines in Heterozygous APE1/Ref-1 Deficient Mice

Background The role of apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) in adipose tissue remains poorly understood. This study investigates adipose tissue dysfunction in heterozygous APE1/Ref-1 deficiency (APE1/Ref-1+/-) mice, focusing on changes in adipocyte physiology, oxidative s...

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Main Authors: Eun-Ok Lee, Hao Jin, Sungmin Kim, Hee Kyoung Joo, Yu Ran Lee, Soo Yeon An, Shuyu Piao, Kwon Ho Lee, Byeong Hwa Jeon
Format: Article
Language:English
Published: Korean Endocrine Society 2024-12-01
Series:Endocrinology and Metabolism
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Online Access:http://www.e-enm.org/upload/pdf/enm-2024-2061.pdf
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author Eun-Ok Lee
Hao Jin
Sungmin Kim
Hee Kyoung Joo
Yu Ran Lee
Soo Yeon An
Shuyu Piao
Kwon Ho Lee
Byeong Hwa Jeon
author_facet Eun-Ok Lee
Hao Jin
Sungmin Kim
Hee Kyoung Joo
Yu Ran Lee
Soo Yeon An
Shuyu Piao
Kwon Ho Lee
Byeong Hwa Jeon
author_sort Eun-Ok Lee
collection DOAJ
description Background The role of apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) in adipose tissue remains poorly understood. This study investigates adipose tissue dysfunction in heterozygous APE1/Ref-1 deficiency (APE1/Ref-1+/-) mice, focusing on changes in adipocyte physiology, oxidative stress, adipokine regulation, and adipose tissue distribution. Methods APE1/Ref-1 mRNA and protein levels in white adipose tissue (WAT) were measured in APE1/Ref-1+/- mice, compared to their wild-type (APE1/Ref-1+/+) controls. Oxidative stress was assessed by evaluating reactive oxygen species (ROS) levels. Histological and immunohistochemical analyses were conducted to observe adipocyte size and macrophage infiltration of WAT. Adipokine expression was measured, and micro-magnetic resonance imaging (MRI) was used to quantify abdominal fat volumes. Results APE1/Ref-1+/- mice exhibited significant reductions in APE1/Ref-1 mRNA and protein levels in WAT and liver tissue. These mice also showed elevated ROS levels, suggesting a regulatory role for APE1/Ref-1 in oxidative stress in WAT and liver. Histological and immunohistochemical analyses revealed hypertrophic adipocytes and macrophage infiltration in WAT, while Oil Red O staining demonstrated enhanced ectopic fat deposition in the liver of APE1/Ref-1+/- mice. These mice also displayed altered adipokine expression, with decreased adiponectin and increased leptin levels in the WAT, along with corresponding alterations in plasma levels. Despite no significant changes in overall body weight, microMRI assessments demonstrated a significant increase in visceral and subcutaneous abdominal fat volumes in APE1/Ref-1+/- mice. Conclusion APE1/Ref-1 is crucial in adipokine regulation and mitigating oxidative stress. These findings suggest its involvement in adipose tissue dysfunction, highlighting its potential impact on abdominal fat distribution and its implications for obesity and oxidative stress-related conditions.
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series Endocrinology and Metabolism
spelling doaj-art-448410dd18034060aa87e8aa0ea34f352025-01-03T05:15:26ZengKorean Endocrine SocietyEndocrinology and Metabolism2093-596X2093-59782024-12-0139693294510.3803/EnM.2024.20612553Alterations in Adipose Tissue and Adipokines in Heterozygous APE1/Ref-1 Deficient MiceEun-Ok Lee0Hao Jin1Sungmin Kim2Hee Kyoung Joo3Yu Ran Lee4Soo Yeon An5Shuyu Piao6Kwon Ho Lee7Byeong Hwa Jeon8 Research Institute of Medical Sciences, Chungnam National University College of Medicine, Daejeon, Korea Department of Physiology, Chungnam National University College of Medicine, Daejeon, Korea Department of Physiology, Chungnam National University College of Medicine, Daejeon, Korea Research Institute of Medical Sciences, Chungnam National University College of Medicine, Daejeon, Korea Research Institute of Medical Sciences, Chungnam National University College of Medicine, Daejeon, Korea Department of Medical Science, Chungnam National University College of Medicine, Daejeon, Korea Research Institute of Medical Sciences, Chungnam National University College of Medicine, Daejeon, Korea Department of Physical Therapy, Joongbu University, Geumsan, Korea Research Institute of Medical Sciences, Chungnam National University College of Medicine, Daejeon, KoreaBackground The role of apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) in adipose tissue remains poorly understood. This study investigates adipose tissue dysfunction in heterozygous APE1/Ref-1 deficiency (APE1/Ref-1+/-) mice, focusing on changes in adipocyte physiology, oxidative stress, adipokine regulation, and adipose tissue distribution. Methods APE1/Ref-1 mRNA and protein levels in white adipose tissue (WAT) were measured in APE1/Ref-1+/- mice, compared to their wild-type (APE1/Ref-1+/+) controls. Oxidative stress was assessed by evaluating reactive oxygen species (ROS) levels. Histological and immunohistochemical analyses were conducted to observe adipocyte size and macrophage infiltration of WAT. Adipokine expression was measured, and micro-magnetic resonance imaging (MRI) was used to quantify abdominal fat volumes. Results APE1/Ref-1+/- mice exhibited significant reductions in APE1/Ref-1 mRNA and protein levels in WAT and liver tissue. These mice also showed elevated ROS levels, suggesting a regulatory role for APE1/Ref-1 in oxidative stress in WAT and liver. Histological and immunohistochemical analyses revealed hypertrophic adipocytes and macrophage infiltration in WAT, while Oil Red O staining demonstrated enhanced ectopic fat deposition in the liver of APE1/Ref-1+/- mice. These mice also displayed altered adipokine expression, with decreased adiponectin and increased leptin levels in the WAT, along with corresponding alterations in plasma levels. Despite no significant changes in overall body weight, microMRI assessments demonstrated a significant increase in visceral and subcutaneous abdominal fat volumes in APE1/Ref-1+/- mice. Conclusion APE1/Ref-1 is crucial in adipokine regulation and mitigating oxidative stress. These findings suggest its involvement in adipose tissue dysfunction, highlighting its potential impact on abdominal fat distribution and its implications for obesity and oxidative stress-related conditions.http://www.e-enm.org/upload/pdf/enm-2024-2061.pdfabdominal fat distributionadipokine expressionadipose tissue dysfunctionape1/ref-1oxidative stress
spellingShingle Eun-Ok Lee
Hao Jin
Sungmin Kim
Hee Kyoung Joo
Yu Ran Lee
Soo Yeon An
Shuyu Piao
Kwon Ho Lee
Byeong Hwa Jeon
Alterations in Adipose Tissue and Adipokines in Heterozygous APE1/Ref-1 Deficient Mice
Endocrinology and Metabolism
abdominal fat distribution
adipokine expression
adipose tissue dysfunction
ape1/ref-1
oxidative stress
title Alterations in Adipose Tissue and Adipokines in Heterozygous APE1/Ref-1 Deficient Mice
title_full Alterations in Adipose Tissue and Adipokines in Heterozygous APE1/Ref-1 Deficient Mice
title_fullStr Alterations in Adipose Tissue and Adipokines in Heterozygous APE1/Ref-1 Deficient Mice
title_full_unstemmed Alterations in Adipose Tissue and Adipokines in Heterozygous APE1/Ref-1 Deficient Mice
title_short Alterations in Adipose Tissue and Adipokines in Heterozygous APE1/Ref-1 Deficient Mice
title_sort alterations in adipose tissue and adipokines in heterozygous ape1 ref 1 deficient mice
topic abdominal fat distribution
adipokine expression
adipose tissue dysfunction
ape1/ref-1
oxidative stress
url http://www.e-enm.org/upload/pdf/enm-2024-2061.pdf
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