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Endocrine
08, 2021;73 (2): 463-471.

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.

Mathis Grossmann, Mark Ng Tang Fui, Tian Nie, Rudolf Hoermann, Michele V Clarke, Ada S Cheung, Jeffrey D Zajac, Rachel A Davey
Author Information
  1. Mathis Grossmann: Department of Medicine Austin Health, University of Melbourne, Heidelberg, Victoria, Australia. ORCID
  2. Mark Ng Tang Fui: Department of Medicine Austin Health, University of Melbourne, Heidelberg, Victoria, Australia. ORCID
  3. Tian Nie: Department of Medicine Austin Health, University of Melbourne, Heidelberg, Victoria, Australia. ORCID
  4. Rudolf Hoermann: Department of Medicine Austin Health, University of Melbourne, Heidelberg, Victoria, Australia. ORCID
  5. Michele V Clarke: Department of Medicine Austin Health, University of Melbourne, Heidelberg, Victoria, Australia.
  6. Ada S Cheung: Department of Medicine Austin Health, University of Melbourne, Heidelberg, Victoria, Australia. ORCID
  7. Jeffrey D Zajac: Department of Medicine Austin Health, University of Melbourne, Heidelberg, Victoria, Australia. ORCID
  8. Rachel A Davey: Department of Medicine Austin Health, University of Melbourne, Heidelberg, Victoria, Australia. r.davey@unimelb.edu.au. ORCID
PMID: 33864607 DOI: 10.1007/s12020-021-02722-0

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/m (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.

Keywords

Gene expression Obesity Testosterone White adipose tissue

Associated Data

ClinicalTrials.gov | NCT01616732

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MeSH Term

Abdominal Fat
Adipose Tissue, White
Child, Preschool
Gene Expression
Humans
Infant
Male
Obesity
Testosterone

Chemicals

Testosterone
Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't
Article has an altmetric score of 1

Word Cloud

Created with Highcharts 10.0.0testosteronemen24receptorsubcutaneousadiposetissueWATgeneexpressionobese8exploratoryweightwhiteloweredserum5receiving[95%CI-6-4placebogenesAngiopoietin-likeSemaphorin3 GNeuropilinAngiopoietinanalysisneuropeptideydietingassociatedupregulationsecretedfactorPURPOSE:aimstudydetermineearlyloss-associatedchangesabdominalRNAnext-generationsequencingMETHODS:FourteenmeanageIQR516years434-54BMI383 kg/m346-40total4 nmol/L75-9providedsamplesbaselineweekslowenergydietRESULTS:Bodylosssimilarparticipantsn = 6-527 kg1726]n = 857 kg10-355]p = 086placebo-treated14410expressedfourupregulatedadjustedfalsediscoveryrateP < 005comparingmost-upregulatedgroupp < 00005CONCLUSIONS:WAT-expressedproteinregulateslipidmetabolismproposedadipocytedifferentiationadipokinewellvascularintegrityinvolvedappetiteregulationstudiesneededconfirmobservationspotentialbiologicalimplicationsTRIALREGISTRATION:clinicaltrialsgovIdentifierNCT01616732Registrationdate:June2012ChangesrandomizedcontroltrialalonecombinationtreatmentGeneObesityTestosteroneWhite

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