Pubertal FGF21 deficit is central in the metabolic pathophysiology of an ovine model of polycystic ovary syndrome
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 clinica...
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Veröffentlicht in: | Molecular and cellular endocrinology 2021-04, Vol.525, p.111196, Article 111196 |
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description | 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 FGF21 signalling 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.
•Prenatal androgenization of female sheep is a model of Polycystic Ovary Syndrome.•Fibroblast Growth Factor 21 is an important metabolic hormone.•Adolescent prenatally androgenized sheep have decreased Fibroblast Growth Factor 21.•Their metabolic profile parallel studies on Fibroblast Growth Factor 21 deficiency.•Targeting this hormone in adolescence may be a therapy in Polycystic Ovary Syndrome. |
doi_str_mv | 10.1016/j.mce.2021.111196 |
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•Prenatal androgenization of female sheep is a model of Polycystic Ovary Syndrome.•Fibroblast Growth Factor 21 is an important metabolic hormone.•Adolescent prenatally androgenized sheep have decreased Fibroblast Growth Factor 21.•Their metabolic profile parallel studies on Fibroblast Growth Factor 21 deficiency.•Targeting this hormone in adolescence may be a therapy in Polycystic Ovary Syndrome.</description><identifier>ISSN: 0303-7207</identifier><identifier>ISSN: 1872-8057</identifier><identifier>EISSN: 1872-8057</identifier><identifier>DOI: 10.1016/j.mce.2021.111196</identifier><identifier>PMID: 33556473</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>Androgens ; Androgens - metabolism ; Animals ; Biomarkers - metabolism ; Chemokines - metabolism ; Disease Models, Animal ; Female ; Fibroblast growth factor 21 (FGF21) ; Fibroblast Growth Factors - deficiency ; Fibroblast Growth Factors - metabolism ; Gene Expression Regulation ; Inflammation - pathology ; Lipids - chemistry ; Liver - metabolism ; Liver - pathology ; Metabolism ; Oxidation-Reduction ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism ; Polycystic ovary syndrome ; Polycystic Ovary Syndrome - genetics ; Polycystic Ovary Syndrome - metabolism ; Polycystic Ovary Syndrome - physiopathology ; Prenatal programming ; Sex Characteristics ; Sexual Maturation ; Sheep ; Signal Transduction ; Subcutaneous Fat - metabolism ; Triglycerides - metabolism</subject><ispartof>Molecular and cellular endocrinology, 2021-04, Vol.525, p.111196, Article 111196</ispartof><rights>2021 Elsevier B.V.</rights><rights>Copyright © 2021 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c396t-d7731e20eedeffeaa0d6cb0d938d63b2d1c27cf19f1b18e043730943474c872f3</citedby><cites>FETCH-LOGICAL-c396t-d7731e20eedeffeaa0d6cb0d938d63b2d1c27cf19f1b18e043730943474c872f3</cites><orcidid>0000-0002-4121-9354 ; 0000-0002-4522-9672 ; 0000-0003-3143-7902</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.mce.2021.111196$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33556473$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Siemienowicz, Katarzyna J.</creatorcontrib><creatorcontrib>Furmanska, Klaudia</creatorcontrib><creatorcontrib>Filis, Panagiotis</creatorcontrib><creatorcontrib>Talia, Chiara</creatorcontrib><creatorcontrib>Thomas, Jennifer</creatorcontrib><creatorcontrib>Fowler, Paul A.</creatorcontrib><creatorcontrib>Rae, Mick T.</creatorcontrib><creatorcontrib>Duncan, W. Colin</creatorcontrib><title>Pubertal FGF21 deficit is central in the metabolic pathophysiology of an ovine model of polycystic ovary syndrome</title><title>Molecular and cellular endocrinology</title><addtitle>Mol Cell Endocrinol</addtitle><description>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 FGF21 signalling 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.
•Prenatal androgenization of female sheep is a model of Polycystic Ovary Syndrome.•Fibroblast Growth Factor 21 is an important metabolic hormone.•Adolescent prenatally androgenized sheep have decreased Fibroblast Growth Factor 21.•Their metabolic profile parallel studies on Fibroblast Growth Factor 21 deficiency.•Targeting this hormone in adolescence may be a therapy in Polycystic Ovary Syndrome.</description><subject>Androgens</subject><subject>Androgens - metabolism</subject><subject>Animals</subject><subject>Biomarkers - metabolism</subject><subject>Chemokines - metabolism</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Fibroblast growth factor 21 (FGF21)</subject><subject>Fibroblast Growth Factors - deficiency</subject><subject>Fibroblast Growth Factors - metabolism</subject><subject>Gene Expression Regulation</subject><subject>Inflammation - pathology</subject><subject>Lipids - chemistry</subject><subject>Liver - metabolism</subject><subject>Liver - pathology</subject><subject>Metabolism</subject><subject>Oxidation-Reduction</subject><subject>Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism</subject><subject>Polycystic ovary syndrome</subject><subject>Polycystic Ovary Syndrome - genetics</subject><subject>Polycystic Ovary Syndrome - metabolism</subject><subject>Polycystic Ovary Syndrome - physiopathology</subject><subject>Prenatal programming</subject><subject>Sex Characteristics</subject><subject>Sexual Maturation</subject><subject>Sheep</subject><subject>Signal Transduction</subject><subject>Subcutaneous Fat - metabolism</subject><subject>Triglycerides - metabolism</subject><issn>0303-7207</issn><issn>1872-8057</issn><issn>1872-8057</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE9LwzAYh4Mobk4_gBfJ0Utn_nRNiycRN4WBHvQc0uSty2ibmmSDfnszph7NJZA8vx_v-yB0TcmcElrcbeedhjkjjM5pOlVxgqa0FCwryUKcoinhhGeCETFBFyFsCSFiwcpzNOF8sShywafo621Xg4-qxcvVklFsoLHaRmwD1tBHnz5sj-MGcAdR1a61Gg8qbtywGYN1rfscsWuw6rHb2z5RzkB7eBlcO-oxxMS7vfIjDmNvvOvgEp01qg1w9XPP0Mfy6f3xOVu_rl4eH9aZ5lURMyMEp8AIQBqpAaWIKXRNTMVLU_CaGaqZ0A2tGlrTEkjOBSdVznOR66Sg4TN0e-wdvPvaQYiys0FD26oe3C5IlpdC5AVNyRmiR1R7F4KHRg7edmloSYk8mJZbmUzLg2l5NJ0yNz_1u7oD85f4VZuA-yMAacm9BS-DttBrMNaDjtI4-0_9Nys1j3c</recordid><startdate>20210405</startdate><enddate>20210405</enddate><creator>Siemienowicz, Katarzyna J.</creator><creator>Furmanska, Klaudia</creator><creator>Filis, Panagiotis</creator><creator>Talia, Chiara</creator><creator>Thomas, Jennifer</creator><creator>Fowler, Paul A.</creator><creator>Rae, Mick T.</creator><creator>Duncan, W. Colin</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-4121-9354</orcidid><orcidid>https://orcid.org/0000-0002-4522-9672</orcidid><orcidid>https://orcid.org/0000-0003-3143-7902</orcidid></search><sort><creationdate>20210405</creationdate><title>Pubertal FGF21 deficit is central in the metabolic pathophysiology of an ovine model of polycystic ovary syndrome</title><author>Siemienowicz, Katarzyna J. ; Furmanska, Klaudia ; Filis, Panagiotis ; Talia, Chiara ; Thomas, Jennifer ; Fowler, Paul A. ; Rae, Mick T. ; Duncan, W. 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Colin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pubertal FGF21 deficit is central in the metabolic pathophysiology of an ovine model of polycystic ovary syndrome</atitle><jtitle>Molecular and cellular endocrinology</jtitle><addtitle>Mol Cell Endocrinol</addtitle><date>2021-04-05</date><risdate>2021</risdate><volume>525</volume><spage>111196</spage><pages>111196-</pages><artnum>111196</artnum><issn>0303-7207</issn><issn>1872-8057</issn><eissn>1872-8057</eissn><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 FGF21 signalling 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.
•Prenatal androgenization of female sheep is a model of Polycystic Ovary Syndrome.•Fibroblast Growth Factor 21 is an important metabolic hormone.•Adolescent prenatally androgenized sheep have decreased Fibroblast Growth Factor 21.•Their metabolic profile parallel studies on Fibroblast Growth Factor 21 deficiency.•Targeting this hormone in adolescence may be a therapy in Polycystic Ovary Syndrome.</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>33556473</pmid><doi>10.1016/j.mce.2021.111196</doi><orcidid>https://orcid.org/0000-0002-4121-9354</orcidid><orcidid>https://orcid.org/0000-0002-4522-9672</orcidid><orcidid>https://orcid.org/0000-0003-3143-7902</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Androgens Androgens - metabolism Animals Biomarkers - metabolism Chemokines - metabolism Disease Models, Animal Female Fibroblast growth factor 21 (FGF21) Fibroblast Growth Factors - deficiency Fibroblast Growth Factors - metabolism Gene Expression Regulation Inflammation - pathology Lipids - chemistry Liver - metabolism Liver - pathology Metabolism Oxidation-Reduction Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism Polycystic ovary syndrome Polycystic Ovary Syndrome - genetics Polycystic Ovary Syndrome - metabolism Polycystic Ovary Syndrome - physiopathology Prenatal programming Sex Characteristics Sexual Maturation Sheep Signal Transduction Subcutaneous Fat - metabolism Triglycerides - metabolism |
title | Pubertal FGF21 deficit is central in the metabolic pathophysiology of an ovine model of polycystic ovary syndrome |
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