Pubertal FGF21 deficit is central in the metabolic pathophysiology of an ovine model of polycystic ovary syndrome

Katarzyna J Siemienowicz* (Corresponding Author), Klaudia Furmanska, Panagiotis Filis, Chiara Talia, Jennifer Thomas, Paul A Fowler , Mick T Rae, W. Colin Duncan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Polycystic ovary syndrome (PCOS), affecting over 10% of women, is associated with insulin resistance, obesity, dyslipidaemia, fatty liver and adipose tissue dysfunction. Its pathogenesis is poorly understood and consequently treatment remains suboptimal. Prenatally androgenized (PA) sheep, a clinically realistic model of PCOS, recapitulate the metabolic problems associated with PCOS. Fibroblast Growth Factor 21 (FGF21) is a metabolic hormone regulating lipid homeostasis, insulin sensitivity, energy balance and adipose tissue function. We therefore investigated the role of FGF21 in the metabolic phenotype of PA sheep. In adolescence PA sheep had decreased hepatic expression and circulating concentrations of FGF21. Adolescent PA sheep show decreased FGF21signalling in subcutaneous adipose tissue, increased hepatic triglyceride content, trend towards reduced fatty acid oxidation capacity and increased hepatic expression of inflammatory markers. These data parallel studies on FGF21 deficiency, suggesting that FGF21 therapy during adolescence may represent a treatment strategy to mitigate metabolic problems associated with PCOS.
Original languageEnglish
Article number111196
Number of pages12
JournalMolecular and Cellular Endocrinology
Volume525
Early online date6 Feb 2021
DOIs
Publication statusPublished - 5 Apr 2021

Keywords

  • polycystic ovaries syndrome
  • Fibroblast Growth Factor 21 (FGF21)
  • metabolism
  • prenatal programming
  • adrogens
  • Polycystic ovary syndrome
  • Androgens
  • Fibroblast growth factor 21 (FGF21)
  • Prenatal programming
  • Metabolism

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