Overexpression of Mitochondrial Catalase within Adipose Tissue Does Not Confer Systemic Metabolic Protection against Diet-Induced Obesity
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Published:2023-05-22
Issue:5
Volume:12
Page:1137
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ISSN:2076-3921
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Container-title:Antioxidants
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language:en
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Short-container-title:Antioxidants
Author:
Croft Amanda J.12, Kelly Conagh23ORCID, Chen Dongqing23, Haw Tatt Jhong12ORCID, Sverdlov Aaron L.124ORCID, Ngo Doan T. M.23
Affiliation:
1. School of Medicine and Public Health, University of Newcastle, Callaghan, NSW 2308, Australia 2. Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia 3. School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW 2308, Australia 4. Hunter New England Local Health District, Newcastle, NSW 2267, Australia
Abstract
Obesity is associated with significant metabolic co-morbidities, such as diabetes, hypertension, and dyslipidaemia, as well as a range of cardiovascular diseases, all of which lead to increased hospitalisations, morbidity, and mortality. Adipose tissue dysfunction caused by chronic nutrient stress can result in oxidative stress, mitochondrial dysfunction, inflammation, hypoxia, and insulin resistance. Thus, we hypothesised that reducing adipose tissue oxidative stress via adipose tissue-targeted overexpression of the antioxidant mitochondrial catalase (mCAT) may improve systemic metabolic function. We crossed mCAT (floxed) and Adipoq-Cre mice to generate mice overexpressing catalase with a mitochondrial targeting sequence predominantly in adipose tissue, designated AdipoQ-mCAT. Under normal diet conditions, the AdipoQ-mCAT transgenic mice demonstrated increased weight gain, adipocyte remodelling, and metabolic dysfunction compared to the wild-type mice. Under obesogenic dietary conditions (16 weeks of high fat/high sucrose feeding), the AdipoQ-mCAT mice did not result in incremental impairment of adipose structure and function but in fact, were protected from further metabolic impairment compared to the obese wild-type mice. While AdipoQ-mCAT overexpression was unable to improve systemic metabolic function per se, our results highlight the critical role of physiological H2O2 signalling in metabolism and adipose tissue function.
Funder
Heart Foundation of Australia Future Leader Fellowship NSW Ministry of Health EMC Fellowship (Australia) and the Heart Foundation of Australia Future Leader Fellowship Vice Chancellor’s HDR Training Scholarship, University of Newcastle Hunter Cancer Research Alliance PhD Scholarship for Translational Cancer Research UNRSC Central Scholarship, University of Newcastle NSW Ministry of Health Cardiovascular Research Capacity Program Early-Mid Career Researcher Grant John Hunter Hospital Charitable Trust Grants
Subject
Cell Biology,Clinical Biochemistry,Molecular Biology,Biochemistry,Physiology
Reference59 articles.
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