Mitochondrial respiration in thoracic perivascular adipose tissue of diabetic mice

in Journal of Endocrinology
Authors:
Aryane Cruz Oliveira Pinho Center for Neuroscience and Cell Biology (CNC), Faculty of Medicine, University of Coimbra, Rua Larga, Coimbra, Portugal
Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, Calçada Martim de Freitas, Coimbra, Portugal

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Diana Santos Center for Neuroscience and Cell Biology (CNC), Faculty of Medicine, University of Coimbra, Rua Larga, Coimbra, Portugal
Institute for Interdisciplinary Research, University of Coimbra, Casa Costa Alemão, Rua Dom Francisco de Lemos, Coimbra, Portugal

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Inês Baldeiras Center for Neuroscience and Cell Biology (CNC), Faculty of Medicine, University of Coimbra, Rua Larga, Coimbra, Portugal

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Ana Burgeiro Center for Neuroscience and Cell Biology (CNC), Faculty of Medicine, University of Coimbra, Rua Larga, Coimbra, Portugal

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Emelindo C Leal Center for Neuroscience and Cell Biology (CNC), Faculty of Medicine, University of Coimbra, Rua Larga, Coimbra, Portugal
Institute for Interdisciplinary Research, University of Coimbra, Casa Costa Alemão, Rua Dom Francisco de Lemos, Coimbra, Portugal

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Eugenia Carvalho Center for Neuroscience and Cell Biology (CNC), Faculty of Medicine, University of Coimbra, Rua Larga, Coimbra, Portugal
Institute for Interdisciplinary Research, University of Coimbra, Casa Costa Alemão, Rua Dom Francisco de Lemos, Coimbra, Portugal
APDP-Portuguese Diabetes Association, Lisbon, Portugal

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Correspondence should be addressed to A C O Pinho or E Carvalho: aryanepinho@cnc.uc.pt or ecarvalh@cnc.uc.pt
DOI:
https://doi.org/10.1530/JOE-21-0446
Volume/Issue:
Volume 254: Issue 3
Article Type:
Research Article
Page Range:
169–184
Online Publication Date:
12 Aug 2022
Copyright:
© Society for Endocrinology 2022
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Introduction

Thoracic perivascular adipose tissue (tPVAT) has a phenotype resembling brown AT. Dysfunctional tPVAT appears to be linked to vascular dysfunction.

Methods

We evaluated uncoupling protein 1 (UCP1) expression by Western blot, oxidative stress by measuring lipid peroxidation, the antioxidant capacity by HPLC and spectrophotometry, and mitochondrial respiration by high-resolution respirometry (HRR) in tPVAT, compared to inguinal white AT (iWAT), obtained from non-diabetic (NDM) and streptozocin-induced diabetic (STZ-DM) mice. Mitochondrial respiration was assessed by HRR using protocol 1: complex I and II oxidative phosphorylation (OXPHOS) and protocol 2: fatty acid oxidation (FAO) OXPHOS. OXPHOS capacity in tPVAT was also evaluated after UCP1 inhibition by guanosine 5'-diphosphate (GDP).

Results

UCP1 expression was higher in tPVAT when compared with iWAT in both NDM and STZ-DM mice. The malondialdehyde concentration was elevated in tPVAT from STZ-DM compared to NDM mice. Glutathione peroxidase and reductase activities, as well as reduced glutathione levels, were not different between tPVAT from NDM and STZ-DM mice but were lower compared to iWAT of STZ-DM mice. OXPHOS capacity of tPVAT was significantly decreased after UCP1 inhibition by GDP in protocol 1. While there were no differences in the OXPHOS capacity between NDM and STZ-DM mice in protocol 1, it was increased in STZ-DM compared to NDM mice in protocol 2. Moreover, complex II- and FAO-linked respiration were elevated in STZ-DM mice under UCP1 inhibition.

Conclusions

Pharmacological therapies could be targeted to modulate UCP1 activity with a significant impact in the uncoupling of mitochondrial bioenergetics in tPVAT.

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© Society for Endocrinology 2022
Page(s):
16
Article Type:
Research Article
Received Date:
26 May 2022
Accepted Date:
14 Jun 2022
Print Publication Date:
01 Sep 2022
Online Publication Date:
12 Aug 2022
Keywords:
thoracic perivascular adipose tissue; mitochondrial respiration; uncoupling protein-1; diabetes

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