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Changes in white adipose tissue gene expression in a randomized control trial of dieting obese men with lowered serum testosterone alone or in combination with testosterone treatment

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Abstract

Purpose

The aim of this study was to determine early weight loss-associated changes in subcutaneous abdominal white adipose tissue (WAT) gene expression in obese men with lowered serum testosterone by RNA next-generation sequencing.

Methods

Fourteen men, mean age (IQR) 51.6 years (43.4–54.5), BMI 38.3 kg/m2 (34.6–40.8) and total testosterone 8.4 nmol/L (7.5–9.5) provided subcutaneous WAT samples at baseline and after 2 weeks of a very low energy diet.

Results

Body weight loss was similar in participants receiving testosterone (n = 6), −5.27 kg [95% CI −6.17; −4.26], and placebo (n = 8), −4.57 kg [95% CI −6.10; −3.55], p = 0.86. In placebo-treated men, of the 14,410 genes expressed in subcutaneous WAT, four genes, Angiopoietin-like 4, Semaphorin 3 G, Neuropilin 2 and Angiopoietin 4, were upregulated (adjusted false discovery rate P < 0.05). In an exploratory analysis comparing men receiving testosterone and placebo, the most-upregulated gene in the testosterone group (exploratory p < 0.0005) was the neuropeptide y receptor 2.

Conclusions

In obese men, dieting is associated with upregulation of WAT-expressed Angiopoietin-like 4, a secreted protein that regulates lipid metabolism, Semaphorin 3 G, a proposed adipocyte differentiation factor and secreted adipokine, and its receptor Neuropilin 2, as well as Angiopoietin 4, a vascular integrity factor. In an exploratory analysis, testosterone was associated with the upregulation of neuropeptide y receptor 2, a receptor involved in appetite regulation. Further studies are needed to confirm these observations and their potential biological implications.

Trial registration

clinicaltrials.gov, Identifier NCT01616732, Registration date: June 8, 2012.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Author contributions

Study design: M.G., J.D.Z. Study conduct: M.N.T.F., M.G. Data collection: M.G., M.N.T.F., M.V.C. Data analysis: M.G., M.N.T.F., T.N., R.A.D. Data interpretation: M.G., M.N.T.F., R.D., A.S.C., J.D.Z., R.A.D. Drafting paper: M.G., M.N.T.F., R.A.D. Approving final version of the paper: all authors.

Funding

Bayer Pharma AG (Berlin, Germany) provided testosterone, placebo and financial support to conduct investigations, but had no role in trial design, data analysis or writing the paper.

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Authors and Affiliations

  1. Department of Medicine Austin Health, University of Melbourne, Heidelberg, Victoria, Australia

    Mathis Grossmann, Mark Ng Tang Fui, Tian Nie, Rudolf Hoermann, Michele V. Clarke, Ada S. Cheung, Jeffrey D. Zajac & Rachel A. Davey

  2. Department of Endocrinology, Austin Health, Heidelberg, Victoria, Australia

    Mathis Grossmann, Mark Ng Tang Fui, Michele V. Clarke, Ada S. Cheung & Jeffrey D. Zajac

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  1. Mathis Grossmann
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  2. Mark Ng Tang Fui
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Corresponding author

Correspondence to Rachel A. Davey.

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Conflict of interest

M.G. has received research funding from Bayer, Novartis, Weight Watchers, Lilly and speaker’s honoraria from Besins Health Care. M.N.T.F. has received research funding from Bayer Pharma. T.N., R.H., J.D.Z. and R.D. have nothing to disclose.

Consent to participate

All participants in the fat biopsy sub-study were required to sign an additional Participant Information and Consent Form (PICF) specifically dedicated to the fat biopsy sub-study explaining the purpose and risks of taking subcutaneous fat biopsies.

Ethics approval

Human Research Ethics Committee, Austin Health (HREC 2012/04495).

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Grossmann, M., Fui, M.N.T., Nie, T. et al. Changes in white adipose tissue gene expression in a randomized control trial of dieting obese men with lowered serum testosterone alone or in combination with testosterone treatment. Endocrine 73, 463–471 (2021). https://doi.org/10.1007/s12020-021-02722-0

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