Androgen reduces mitochondrial respiration in mouse brown adipocytes: a model for disordered energy balance in polycystic ovary syndrome

Lerner, A., Kewada, D., Ahmed, A., Hardy, K., Christian, M. ORCID: 0000-0002-1616-4179 and Franks, S., 2020. Androgen reduces mitochondrial respiration in mouse brown adipocytes: a model for disordered energy balance in polycystic ovary syndrome. International Journal of Molecular Sciences, 22 (1): 243. ISSN 1661-6596

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Abstract

Polycystic ovary syndrome (PCOS) is a common endocrinopathy that is associated with an adverse metabolic profile including reduced postprandial thermogenesis. Although abnormalities in adipose tissue function have been widely reported in women with PCOS, less is known about direct effects of androgen on white and, particularly, brown adipocytes. The purpose of this study was to investigate the effect of the nonaromatizable androgen dihydrotestosterone (DHT) on (1) lipid accumulation and expression of adipogenic markers in immortalized mouse brown adipose cell lines (IMBATs), (2) mitochondrial respiration in IMBATs, (3) mitochondrial DNA content and gene expression, (4) expression of brown adipose tissue (BAT) markers and thermogenic activation. In addition, we profiled the relative levels of 38 adipokines secreted from BAT explants and looked at androgen effects on adipokine gene expression in both IMBATs and immortalized mouse white adipose (IMWATs) cell lines. Androgen treatment inhibited IMBAT differentiation in a dose-dependent manner, reduced markers of adipogenesis, and attenuated the β-adrenoceptor-stimulated increase in uncoupling protein-1 (UCP1) expression. In explants of mouse interscapular BAT, androgen reduced expression of UCP1, peroxisome proliferator-activated receptor-γ coactivator-1 (PCG-1) and Cidea. Significantly, as well as affecting genes involved in thermogenesis in BAT, androgen treatment reduced mitochondrial respiration in IMBATs, as measured by the Seahorse XF method. The results of this study suggest a role for excess androgen in inhibiting brown adipogenesis, attenuating the activation of thermogenesis and reducing mitochondrial respiration in BAT. Together, these data provide a plausible molecular mechanism that may contribute to reduced postprandial thermogenesis and the tendency to obesity in women with PCOS.

Item Type: Journal article
Publication Title: International Journal of Molecular Sciences
Creators: Lerner, A., Kewada, D., Ahmed, A., Hardy, K., Christian, M. and Franks, S.
Publisher: MDPI
Date: 29 December 2020
Volume: 22
Number: 1
ISSN: 1661-6596
Identifiers:
NumberType
10.3390/ijms22010243DOI
1398041Other
Divisions: Schools > School of Science and Technology
Record created by: Jonathan Gallacher
Date Added: 11 Jan 2021 10:32
Last Modified: 11 Jan 2021 10:32
URI: http://irep.ntu.ac.uk/id/eprint/41992

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