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Kaikaew K, Grefhorst A, Steenbergen J, et al. Sex difference in the mouse BAT transcriptome reveals a role of progesterone. J Mol Endocrinol. 2021;66(2):97-113doi: 10.1530/JME-20-0210.
Kaikaew, K., Grefhorst, A., Steenbergen, J., Swagemakers, S. M. A., McLuskey, A., & Visser, J. A. (2021). Sex difference in the mouse BAT transcriptome reveals a role of progesterone. Journal of molecular endocrinology, 66(2), 97-113. https://doi.org/10.1530/JME-20-0210
Kaikaew, Kasiphak, et al. "Sex difference in the mouse BAT transcriptome reveals a role of progesterone." Journal of molecular endocrinology vol. 66,2 (2021): 97-113. doi: https://doi.org/10.1530/JME-20-0210
Kaikaew K, Grefhorst A, Steenbergen J, Swagemakers SMA, McLuskey A, Visser JA. Sex difference in the mouse BAT transcriptome reveals a role of progesterone. J Mol Endocrinol. 2021 Feb;66(2):97-113. doi: 10.1530/JME-20-0210. PMID: 33263559.
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J Mol Endocrinol. 2021 Feb;66(2):97-113. doi: 10.1530/JME-20-0210.

Sex difference in the mouse BAT transcriptome reveals a role of progesterone.

Journal of molecular endocrinology

Kasiphak Kaikaew, Aldo Grefhorst, Jacobie Steenbergen, Sigrid M A Swagemakers, Anke McLuskey, Jenny A Visser

Affiliations

  1. Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
  2. Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
  3. Department of Experimental Vascular Medicine, Amsterdam University Medical Centers, Location AMC, Amsterdam, the Netherlands.
  4. Department of Pathology and Clinical Bioinformatics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.

PMID: 33263559 DOI: 10.1530/JME-20-0210

Abstract

Brown adipose tissue (BAT) is a metabolically active organ that exhibits sex-differential features, that is, being generally more abundant and active in females than in males. Although sex steroids, particularly estrogens, have been shown to regulate BAT thermogenic function, the underlying molecular mechanisms contributing to sexual dimorphism in basal BAT activity have not been elucidated. Therefore, we assessed the transcriptome of interscapular BAT of male and female C57BL/6J mice by RNA sequencing and identified 295 genes showing ≥2-fold differential expression (adjusted P < 0.05). In silico functional annotation clustering suggested an enrichment of genes encoding proteins involved in cell-cell contact, interaction, and adhesion. Ovariectomy reduced the expression of these genes in female BAT toward a male pattern whereas orchiectomy had marginal effects on the transcriptional pattern, indicating a prominent role of female gonadal hormones in this sex-differential expression pattern. Progesterone was identified as a possible upstream regulator of the sex-differentially expressed genes. Studying the direct effects of progesterone in vitro in primary adipocytes showed that progesterone significantly altered the transcription of several of the identified genes, possibly via the glucocorticoid receptor. In conclusion, this study reveals a sexually dimorphic transcription profile in murine BAT at general housing conditions and demonstrates a role for progesterone in the regulation of the interscapular BAT transcriptome.

Keywords: RNA sequencing; brown adipose tissue; gonadal steroid hormones; primary cell culture; sex characteristics

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