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

Katarzyna  J Siemienowicz; Klaudia  Furmanska; Panagiotis Filis; Chiara Talia; Jennifer  Thomas; Paul A Fowler; Mick T Rae; W. Colin Duncan

doi:10.1016/j.mce.2021.111196

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 journal › Article › peer-review

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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 language	English
Article number	111196
Number of pages	12
Journal	Molecular and Cellular Endocrinology
Volume	525
Early online date	6 Feb 2021
DOIs	https://doi.org/10.1016/j.mce.2021.111196
Publication status	Published - 5 Apr 2021

Bibliographical note

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).

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Cite this

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

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.",

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author = "Siemienowicz, {Katarzyna J} and Klaudia Furmanska and Panagiotis Filis and Chiara Talia and Jennifer Thomas and Fowler, {Paul A} and Rae, {Mick T} and {Colin Duncan}, W.",

note = "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). ",

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AU - Siemienowicz, Katarzyna J

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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).

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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.

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

Abstract

Bibliographical note

Keywords

UN SDGs

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