The AR in bone marrow progenitor cells protects against short-term high-caloric diet-induced weight gain in male mice

in Journal of Molecular Endocrinology
Authors:
Varun S Venkatesh Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Victoria, Australia

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Patricia K Russell Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Victoria, Australia

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Barbara Fam White Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Victoria, Australia

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Michele V Clarke Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Victoria, Australia

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Suzanne Golub Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Victoria, Australia

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Salvatore Mangiofico Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Victoria, Australia

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Christian Haralambous Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Victoria, Australia

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Julie Lokan Department of Anatomical Pathology, Austin Health, Heidelberg, Victoria, Australia

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Sof Andrikopoulos Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Victoria, Australia

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Jeffrey D Zajac Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Victoria, Australia

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Rachel A Davey Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Victoria, Australia

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https://orcid.org/0000-0001-5121-0209

Correspondence should be addressed to R A Davey: r.davey@unimelb.edu.au
DOI:
https://doi.org/10.1530/JME-22-0038
Volume/Issue:
Volume 69: Issue 1
Article Type:
Research Article
Page Range:
269–283
Online Publication Date:
10 May 2022
Copyright:
© Society for Endocrinology 2022
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We previously identified a novel pathway of testosterone action via the androgen receptor (AR) in bone marrow mesenchymal precursor cells (BM-PCs) to negatively regulate fat mass and improve metabolic function in male mice. This was achieved using our PC-AR Gene Replacement mouse model in which the AR is only expressed in BM-PCs and deleted in all other tissues. We hypothesise that the markedly reduced fat mass and increased insulin sensitivity of PC-AR Gene Replacements will confer protection from diet-induced overweight and obesity. To test this, 6-week-old male PC-AR Gene Replacements and controls (WT, global-AR knockouts (KOs)) were fed a chow or high-caloric diet (HCD) for 8 or 18 weeks. Following 8 weeks (short-term) of HCD, WT and Global-ARKOs had markedly increased subcutaneous white adipose tissue (WAT) and retroperitoneal visceral adipose tissue (VAT) mass compared to chow-fed controls. In contrast, PC-AR Gene Replacements were resistant to WAT and VAT accumulation following short-term HCD feeding accompanied by fewer large adipocytes and upregulation of expression of the metabolic genes Acaca and Pnlpa2. Following long-term HCD feeding for 18 weeks, the PC-AR Gene Replacements were no longer resistant to increased WAT and VAT adiposity, however, maintained their improved whole-body insulin sensitivity with an increased rate of glucose disappearance and increased glucose uptake into subcutaneous WAT. In conclusion, the action of testosterone via the AR in BM-PCs to negatively regulate fat mass and improve metabolism confers resistance from short-term diet-induced weight gain and partial protection from long-term diet-induced obesity in male mice.

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Online ISSN:
1479-6813
Print ISSN:
0952-5041
Copyright:
© Society for Endocrinology 2022
Page(s):
15
Article Type:
Research Article
Received Date:
09 Mar 2022
Accepted Date:
31 Mar 2022
Print Publication Date:
01 Jul 2022
Online Publication Date:
10 May 2022
Keywords:
androgens; androgen receptors; adipose tissue; obesity; bone

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