Loss of Trim28 in muscle alters mitochondrial signalling but not systemic metabolism

in Journal of Endocrinology
Authors:
Emily J King Baker Heart & Diabetes Institute, Melbourne, Victoria, Australia
Central Clinical School, Monash University, Melbourne, Victoria, Australia

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Simon T Bond Baker Heart & Diabetes Institute, Melbourne, Victoria, Australia
Central Clinical School, Monash University, Melbourne, Victoria, Australia
Baker Department of Cardiometabolic Health, The University of Melbourne, Melbourne, Australia

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https://orcid.org/0000-0003-1551-8614
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Christine Yang Baker Heart & Diabetes Institute, Melbourne, Victoria, Australia

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Yingying Liu Baker Heart & Diabetes Institute, Melbourne, Victoria, Australia

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Anna C Calkin Baker Heart & Diabetes Institute, Melbourne, Victoria, Australia
Central Clinical School, Monash University, Melbourne, Victoria, Australia
Baker Department of Cardiometabolic Health, The University of Melbourne, Melbourne, Australia

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Darren C Henstridge Baker Heart & Diabetes Institute, Melbourne, Victoria, Australia
School of Health Sciences, University of Tasmania, Launceston, Tasmania, Australia

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https://orcid.org/0000-0003-4988-767X
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Brian G Drew Baker Heart & Diabetes Institute, Melbourne, Victoria, Australia
Central Clinical School, Monash University, Melbourne, Victoria, Australia
Baker Department of Cardiometabolic Health, The University of Melbourne, Melbourne, Australia

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https://orcid.org/0000-0002-7839-9467

Correspondence should be addressed to D Henstridge or B G Drew: darren.henstridge@utas.edu.au or brian.drew@baker.edu.au
DOI:
https://doi.org/10.1530/JOE-23-0210
Volume/Issue:
Volume 259: Issue 2
Article Type:
Research Article
Article ID:
e230210
Online Publication Date:
09 Oct 2023
Copyright:
© the author(s) 2023
Restricted access
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Type 2 diabetes mellitus (T2DM), a condition characterised by insulin resistance (IR) and skeletal muscle mitochondrial abnormalities, is a leading cause of death in developed societies. Much work has postulated that improving pathways linked to mitochondrial health, including autophagy, may be a potential avenue to prevent or treat T2DM. Given the recent data indicating a role for tripartite motif-containing 28 (TRIM28) in autophagy and mitochondrial pathways, we investigated whether muscle-specific deletion of TRIM28 might impact on obesity, glucose tolerance, and IR in mice. We studied two different muscle-specific (MCK-cre and ACTA1-cre-ERT2) TRIM28 knockout models, which were phenotyped during and after being fed a chow or high-fat diet (HFD). Whilst muscle-specific deletion of TRIM28 in both models demonstrated alterations in markers of mitochondrial activity and autophagy in skeletal muscle, we did not observe major impacts on the majority of metabolic measures in these mice. Specifically, we demonstrate that deletion of TRIM28 in skeletal muscle of mice during (MCK-cre) or post-development (ACTA1-cre-ERT2) does not prevent HFD-induced obesity or glucose intolerance. These findings are consistent with those reported previously in relation to autophagy and mitochondria in other cell types, and thus warrant further study into the biological role TRIM28 has in relation to mitochondrial function.

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© the author(s) 2023
Article ID:
e230210
Article Type:
Research Article
Received Date:
29 Jun 2023
Accepted Date:
19 Sep 2023
Print Publication Date:
01 Nov 2023
Online Publication Date:
09 Oct 2023
Keywords:
TRIM28; mitochondria; skeletal muscle; glucose tolerance; metabolism

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