TY - JOUR
T1 - Pubertal FGF21 deficit is central in the metabolic pathophysiology of an ovine model of polycystic ovary syndrome
AU - Siemienowicz, Katarzyna J
AU - Furmanska, Klaudia
AU - Filis, Panagiotis
AU - Talia, Chiara
AU - Thomas, Jennifer
AU - Fowler , Paul A
AU - Rae, Mick T
AU - Colin Duncan, W.
N1 - Acknowledgements
The authors wish to acknowledge Joan Docherty, John Hogg, Marjorie Thomson, Peter Tennant and James Nixon and the staff at the Marshall Building, University of Edinburgh for their excellent animal husbandry. Dr Kirsten Hogg, Dr Fiona Connolly, Dr Junko Nio443 Kobayashi, Dr Avi Lerner and Lyndsey Boswell helped with tissue collection.
Funding
This work was funded by Medical Research Council (MRC) project grants (G0500717; G0801807; G0802782; MR/P011535/1) and supported by the MRC Centre for Reproductive Health (MR/N022556/1).
PY - 2021/4/5
Y1 - 2021/4/5
N2 - 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.
AB - 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.
KW - polycystic ovaries syndrome
KW - Fibroblast Growth Factor 21 (FGF21)
KW - metabolism
KW - prenatal programming
KW - adrogens
KW - Polycystic ovary syndrome
KW - Androgens
KW - Fibroblast growth factor 21 (FGF21)
KW - Prenatal programming
KW - Metabolism
UR - http://www.scopus.com/inward/record.url?scp=85100622422&partnerID=8YFLogxK
U2 - 10.1016/j.mce.2021.111196
DO - 10.1016/j.mce.2021.111196
M3 - Article
C2 - 33556473
VL - 525
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
SN - 0303-7207
M1 - 111196
ER -
