Effect of GLP-1 Receptor Agonists in the Cardiometabolic Complications in a Rat Model of Postmenopausal PCOS
Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and ovulatory dysfunction. Women with PCOS have an elevated prevalence of cardiometabolic risk factors that worsen after menopause. Liraglutide (Lira), a glucagon-like peptide-1 receptor agonist, has shown beneficial metabolic eff...
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| Veröffentlicht in: | Endocrinology (Philadelphia) 2019-12, Vol.160 (12), p.2787-2799 |
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| creator | Torres Fernandez, Edgar D Huffman, Alexandra M Syed, Maryam Romero, Damian G Yanes Cardozo, Licy L |
| description | Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and ovulatory dysfunction. Women with PCOS have an elevated prevalence of cardiometabolic risk factors that worsen after menopause. Liraglutide (Lira), a glucagon-like peptide-1 receptor agonist, has shown beneficial metabolic effects in small clinic trials in reproductive-age women with PCOS. We have shown that chronic hyperandrogenemia in an experimental model of postmenopausal PCOS is associated with an adverse cardiometabolic profile and upregulation of the intrarenal renin-angiotensin system (RAS). We analyzed the effect of Lira in the cardiometabolic profile, intrarenal RAS, and blood pressure (BP) in postmenopausal PCOS. Four-week-old female Sprague Dawley rats were treated with DHT or placebo for 17 months. Lira administration during the last 3 weeks caused a bigger reduction in food intake, body weight, fat mass, and homeostasis model assessment of insulin resistance index in PCOS than in control rats. Moreover, Lira improved dyslipidemia and elevated leptin levels in PCOS. In contrast, Lira decreased intrarenal expression of RAS components only in the control group. Lira transiently increased heart rate and decreased BP in control rats. However, Lira did not modify BP but increased heart rate in PCOS. The angiotensin-converting-enzyme inhibitor enalapril abolished the BP differences between PCOS and control rats. However, Lira coadministration with enalapril further reduced BP only in control rats. In summary, Lira has beneficial effects for several cardiometabolic risk factors in postmenopausal PCOS. However, hyperandrogenemia blunted the BP-lowering effect of Lira in postmenopausal PCOS. Androgen-induced activation of intrarenal RAS may play a major role mediating increases in BP in postmenopausal PCOS. |
| doi_str_mv | 10.1210/en.2019-00450 |
| format | Article |
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Women with PCOS have an elevated prevalence of cardiometabolic risk factors that worsen after menopause. Liraglutide (Lira), a glucagon-like peptide-1 receptor agonist, has shown beneficial metabolic effects in small clinic trials in reproductive-age women with PCOS. We have shown that chronic hyperandrogenemia in an experimental model of postmenopausal PCOS is associated with an adverse cardiometabolic profile and upregulation of the intrarenal renin-angiotensin system (RAS). We analyzed the effect of Lira in the cardiometabolic profile, intrarenal RAS, and blood pressure (BP) in postmenopausal PCOS. Four-week-old female Sprague Dawley rats were treated with DHT or placebo for 17 months. Lira administration during the last 3 weeks caused a bigger reduction in food intake, body weight, fat mass, and homeostasis model assessment of insulin resistance index in PCOS than in control rats. Moreover, Lira improved dyslipidemia and elevated leptin levels in PCOS. In contrast, Lira decreased intrarenal expression of RAS components only in the control group. Lira transiently increased heart rate and decreased BP in control rats. However, Lira did not modify BP but increased heart rate in PCOS. The angiotensin-converting-enzyme inhibitor enalapril abolished the BP differences between PCOS and control rats. However, Lira coadministration with enalapril further reduced BP only in control rats. In summary, Lira has beneficial effects for several cardiometabolic risk factors in postmenopausal PCOS. However, hyperandrogenemia blunted the BP-lowering effect of Lira in postmenopausal PCOS. Androgen-induced activation of intrarenal RAS may play a major role mediating increases in BP in postmenopausal PCOS.</description><identifier>ISSN: 1945-7170</identifier><identifier>ISSN: 0013-7227</identifier><identifier>EISSN: 1945-7170</identifier><identifier>DOI: 10.1210/en.2019-00450</identifier><identifier>PMID: 31593246</identifier><language>eng</language><publisher>United States: Oxford University Press</publisher><subject>Agonists ; Angiotensin-converting enzyme inhibitors ; Animals ; Blood pressure ; Blood Pressure - drug effects ; Body Composition - drug effects ; Body fat ; Body weight ; Body Weight - drug effects ; Complications ; Complications and side effects ; Disease Models, Animal ; Drug Evaluation, Preclinical ; Dyslipidemia ; Eating - drug effects ; Endocrinology ; Enzyme inhibitors ; Female ; Food intake ; Genetic aspects ; GLP-1 receptor agonists ; Glucagon ; Glucagon-like peptide 1 ; Glucagon-Like Peptide-1 Receptor - agonists ; Health aspects ; Health risks ; Heart rate ; Heart Rate - drug effects ; Homeostasis ; Hyperandrogenism - complications ; Hypertension ; Insulin ; Insulin Resistance ; Leptin ; Leptin - blood ; Lipids - blood ; Liraglutide - pharmacology ; Liraglutide - therapeutic use ; Menopause ; Metabolic Syndrome - etiology ; Metabolic Syndrome - prevention & control ; Peptide hormones ; Peptidyl-dipeptidase A ; Polycystic ovary syndrome ; Polycystic Ovary Syndrome - complications ; Post-menopause ; Postmenopause ; Random Allocation ; Rats, Sprague-Dawley ; Renin ; Renin-angiotensin system ; Renin-Angiotensin System - drug effects ; Risk analysis ; Risk factors ; Rodents ; Stein-Leventhal syndrome</subject><ispartof>Endocrinology (Philadelphia), 2019-12, Vol.160 (12), p.2787-2799</ispartof><rights>Copyright © 2019 Endocrine Society.</rights><rights>COPYRIGHT 2019 Oxford University Press</rights><rights>Copyright © 2019 Endocrine Society</rights><rights>Copyright © 2019 Endocrine Society 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c482t-5594373bffab3d5e6819ec085f9a903872c7e6c6dbc8ce1b13840fccd9e67aa23</citedby><cites>FETCH-LOGICAL-c482t-5594373bffab3d5e6819ec085f9a903872c7e6c6dbc8ce1b13840fccd9e67aa23</cites><orcidid>0000-0002-7295-1871 ; 0000-0002-8378-4394 ; 0000-0002-7268-9690</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31593246$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Torres Fernandez, Edgar D</creatorcontrib><creatorcontrib>Huffman, Alexandra M</creatorcontrib><creatorcontrib>Syed, Maryam</creatorcontrib><creatorcontrib>Romero, Damian G</creatorcontrib><creatorcontrib>Yanes Cardozo, Licy L</creatorcontrib><title>Effect of GLP-1 Receptor Agonists in the Cardiometabolic Complications in a Rat Model of Postmenopausal PCOS</title><title>Endocrinology (Philadelphia)</title><addtitle>Endocrinology</addtitle><description>Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and ovulatory dysfunction. Women with PCOS have an elevated prevalence of cardiometabolic risk factors that worsen after menopause. Liraglutide (Lira), a glucagon-like peptide-1 receptor agonist, has shown beneficial metabolic effects in small clinic trials in reproductive-age women with PCOS. We have shown that chronic hyperandrogenemia in an experimental model of postmenopausal PCOS is associated with an adverse cardiometabolic profile and upregulation of the intrarenal renin-angiotensin system (RAS). We analyzed the effect of Lira in the cardiometabolic profile, intrarenal RAS, and blood pressure (BP) in postmenopausal PCOS. Four-week-old female Sprague Dawley rats were treated with DHT or placebo for 17 months. Lira administration during the last 3 weeks caused a bigger reduction in food intake, body weight, fat mass, and homeostasis model assessment of insulin resistance index in PCOS than in control rats. Moreover, Lira improved dyslipidemia and elevated leptin levels in PCOS. In contrast, Lira decreased intrarenal expression of RAS components only in the control group. Lira transiently increased heart rate and decreased BP in control rats. However, Lira did not modify BP but increased heart rate in PCOS. The angiotensin-converting-enzyme inhibitor enalapril abolished the BP differences between PCOS and control rats. However, Lira coadministration with enalapril further reduced BP only in control rats. In summary, Lira has beneficial effects for several cardiometabolic risk factors in postmenopausal PCOS. However, hyperandrogenemia blunted the BP-lowering effect of Lira in postmenopausal PCOS. Androgen-induced activation of intrarenal RAS may play a major role mediating increases in BP in postmenopausal PCOS.</description><subject>Agonists</subject><subject>Angiotensin-converting enzyme inhibitors</subject><subject>Animals</subject><subject>Blood pressure</subject><subject>Blood Pressure - drug effects</subject><subject>Body Composition - drug effects</subject><subject>Body fat</subject><subject>Body weight</subject><subject>Body Weight - drug effects</subject><subject>Complications</subject><subject>Complications and side effects</subject><subject>Disease Models, Animal</subject><subject>Drug Evaluation, Preclinical</subject><subject>Dyslipidemia</subject><subject>Eating - drug effects</subject><subject>Endocrinology</subject><subject>Enzyme inhibitors</subject><subject>Female</subject><subject>Food intake</subject><subject>Genetic aspects</subject><subject>GLP-1 receptor agonists</subject><subject>Glucagon</subject><subject>Glucagon-like peptide 1</subject><subject>Glucagon-Like Peptide-1 Receptor - agonists</subject><subject>Health aspects</subject><subject>Health risks</subject><subject>Heart rate</subject><subject>Heart Rate - drug effects</subject><subject>Homeostasis</subject><subject>Hyperandrogenism - complications</subject><subject>Hypertension</subject><subject>Insulin</subject><subject>Insulin Resistance</subject><subject>Leptin</subject><subject>Leptin - blood</subject><subject>Lipids - blood</subject><subject>Liraglutide - pharmacology</subject><subject>Liraglutide - therapeutic use</subject><subject>Menopause</subject><subject>Metabolic Syndrome - etiology</subject><subject>Metabolic Syndrome - prevention & control</subject><subject>Peptide hormones</subject><subject>Peptidyl-dipeptidase A</subject><subject>Polycystic ovary syndrome</subject><subject>Polycystic Ovary Syndrome - complications</subject><subject>Post-menopause</subject><subject>Postmenopause</subject><subject>Random Allocation</subject><subject>Rats, Sprague-Dawley</subject><subject>Renin</subject><subject>Renin-angiotensin system</subject><subject>Renin-Angiotensin System - drug effects</subject><subject>Risk analysis</subject><subject>Risk factors</subject><subject>Rodents</subject><subject>Stein-Leventhal syndrome</subject><issn>1945-7170</issn><issn>0013-7227</issn><issn>1945-7170</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkk1v1DAQhiMEoh9w5IosceGSxZ9JfEFaRW1BWtRVgbPlOOOtq8QOtoPEvydpS2kRmsOMxs-8o7HeonhD8IZQgj-A31BMZIkxF_hZcUwkF2VNavz8UX1UnKR0gzHhnLOXxREjQjLKq-NiOLMWTEbBoovdviToCgxMOUS0PQTvUk7IeZSvAbU69i6MkHUXBmdQG8ZpyTq74G8hja50Rl9CD8Mqtw8pj-DDpOekB7RvL7--Kl5YPSR4fZ9Pi-_nZ9_aT-Xu8uJzu92Vhjc0l0JIzmrWWas71guoGiLB4EZYqSVmTU1NDZWp-s40BkhHWMOxNaaXUNVaU3ZafLzTneZuhN6Az1EPaopu1PGXCtqppy_eXatD-KmqhgpBqkXg_b1ADD9mSFmNLhkYBu0hzElRhimvKRbrrnf_oDdhjn45b6EqQUldc_yXOugBlPM2LHvNKqq2FRFcYin4Qm3-Qy3Rw-hM8GDd0n8yUN4NmBhSimAfbiRYrfZQ4NVqD3Vrj4V_-_hjHug_fmC_AdTCtBU</recordid><startdate>20191201</startdate><enddate>20191201</enddate><creator>Torres Fernandez, Edgar D</creator><creator>Huffman, Alexandra M</creator><creator>Syed, Maryam</creator><creator>Romero, Damian G</creator><creator>Yanes Cardozo, Licy L</creator><general>Oxford University Press</general><general>Endocrine Society</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>7QG</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-7295-1871</orcidid><orcidid>https://orcid.org/0000-0002-8378-4394</orcidid><orcidid>https://orcid.org/0000-0002-7268-9690</orcidid></search><sort><creationdate>20191201</creationdate><title>Effect of GLP-1 Receptor Agonists in the Cardiometabolic Complications in a Rat Model of Postmenopausal PCOS</title><author>Torres Fernandez, Edgar D ; Huffman, Alexandra M ; Syed, Maryam ; Romero, Damian G ; Yanes Cardozo, Licy L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c482t-5594373bffab3d5e6819ec085f9a903872c7e6c6dbc8ce1b13840fccd9e67aa23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Agonists</topic><topic>Angiotensin-converting enzyme inhibitors</topic><topic>Animals</topic><topic>Blood pressure</topic><topic>Blood Pressure - drug effects</topic><topic>Body Composition - drug effects</topic><topic>Body fat</topic><topic>Body weight</topic><topic>Body Weight - drug effects</topic><topic>Complications</topic><topic>Complications and side effects</topic><topic>Disease Models, Animal</topic><topic>Drug Evaluation, Preclinical</topic><topic>Dyslipidemia</topic><topic>Eating - drug effects</topic><topic>Endocrinology</topic><topic>Enzyme inhibitors</topic><topic>Female</topic><topic>Food intake</topic><topic>Genetic aspects</topic><topic>GLP-1 receptor agonists</topic><topic>Glucagon</topic><topic>Glucagon-like peptide 1</topic><topic>Glucagon-Like Peptide-1 Receptor - agonists</topic><topic>Health aspects</topic><topic>Health risks</topic><topic>Heart rate</topic><topic>Heart Rate - drug effects</topic><topic>Homeostasis</topic><topic>Hyperandrogenism - complications</topic><topic>Hypertension</topic><topic>Insulin</topic><topic>Insulin Resistance</topic><topic>Leptin</topic><topic>Leptin - blood</topic><topic>Lipids - blood</topic><topic>Liraglutide - pharmacology</topic><topic>Liraglutide - therapeutic use</topic><topic>Menopause</topic><topic>Metabolic Syndrome - etiology</topic><topic>Metabolic Syndrome - prevention & control</topic><topic>Peptide hormones</topic><topic>Peptidyl-dipeptidase A</topic><topic>Polycystic ovary syndrome</topic><topic>Polycystic Ovary Syndrome - complications</topic><topic>Post-menopause</topic><topic>Postmenopause</topic><topic>Random Allocation</topic><topic>Rats, Sprague-Dawley</topic><topic>Renin</topic><topic>Renin-angiotensin system</topic><topic>Renin-Angiotensin System - drug effects</topic><topic>Risk analysis</topic><topic>Risk factors</topic><topic>Rodents</topic><topic>Stein-Leventhal syndrome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Torres Fernandez, Edgar D</creatorcontrib><creatorcontrib>Huffman, Alexandra M</creatorcontrib><creatorcontrib>Syed, Maryam</creatorcontrib><creatorcontrib>Romero, Damian G</creatorcontrib><creatorcontrib>Yanes Cardozo, Licy L</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Endocrinology (Philadelphia)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Torres Fernandez, Edgar D</au><au>Huffman, Alexandra M</au><au>Syed, Maryam</au><au>Romero, Damian G</au><au>Yanes Cardozo, Licy L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of GLP-1 Receptor Agonists in the Cardiometabolic Complications in a Rat Model of Postmenopausal PCOS</atitle><jtitle>Endocrinology (Philadelphia)</jtitle><addtitle>Endocrinology</addtitle><date>2019-12-01</date><risdate>2019</risdate><volume>160</volume><issue>12</issue><spage>2787</spage><epage>2799</epage><pages>2787-2799</pages><issn>1945-7170</issn><issn>0013-7227</issn><eissn>1945-7170</eissn><abstract>Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and ovulatory dysfunction. Women with PCOS have an elevated prevalence of cardiometabolic risk factors that worsen after menopause. Liraglutide (Lira), a glucagon-like peptide-1 receptor agonist, has shown beneficial metabolic effects in small clinic trials in reproductive-age women with PCOS. We have shown that chronic hyperandrogenemia in an experimental model of postmenopausal PCOS is associated with an adverse cardiometabolic profile and upregulation of the intrarenal renin-angiotensin system (RAS). We analyzed the effect of Lira in the cardiometabolic profile, intrarenal RAS, and blood pressure (BP) in postmenopausal PCOS. Four-week-old female Sprague Dawley rats were treated with DHT or placebo for 17 months. Lira administration during the last 3 weeks caused a bigger reduction in food intake, body weight, fat mass, and homeostasis model assessment of insulin resistance index in PCOS than in control rats. Moreover, Lira improved dyslipidemia and elevated leptin levels in PCOS. In contrast, Lira decreased intrarenal expression of RAS components only in the control group. Lira transiently increased heart rate and decreased BP in control rats. However, Lira did not modify BP but increased heart rate in PCOS. The angiotensin-converting-enzyme inhibitor enalapril abolished the BP differences between PCOS and control rats. However, Lira coadministration with enalapril further reduced BP only in control rats. In summary, Lira has beneficial effects for several cardiometabolic risk factors in postmenopausal PCOS. However, hyperandrogenemia blunted the BP-lowering effect of Lira in postmenopausal PCOS. Androgen-induced activation of intrarenal RAS may play a major role mediating increases in BP in postmenopausal PCOS.</abstract><cop>United States</cop><pub>Oxford University Press</pub><pmid>31593246</pmid><doi>10.1210/en.2019-00450</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-7295-1871</orcidid><orcidid>https://orcid.org/0000-0002-8378-4394</orcidid><orcidid>https://orcid.org/0000-0002-7268-9690</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Agonists Angiotensin-converting enzyme inhibitors Animals Blood pressure Blood Pressure - drug effects Body Composition - drug effects Body fat Body weight Body Weight - drug effects Complications Complications and side effects Disease Models, Animal Drug Evaluation, Preclinical Dyslipidemia Eating - drug effects Endocrinology Enzyme inhibitors Female Food intake Genetic aspects GLP-1 receptor agonists Glucagon Glucagon-like peptide 1 Glucagon-Like Peptide-1 Receptor - agonists Health aspects Health risks Heart rate Heart Rate - drug effects Homeostasis Hyperandrogenism - complications Hypertension Insulin Insulin Resistance Leptin Leptin - blood Lipids - blood Liraglutide - pharmacology Liraglutide - therapeutic use Menopause Metabolic Syndrome - etiology Metabolic Syndrome - prevention & control Peptide hormones Peptidyl-dipeptidase A Polycystic ovary syndrome Polycystic Ovary Syndrome - complications Post-menopause Postmenopause Random Allocation Rats, Sprague-Dawley Renin Renin-angiotensin system Renin-Angiotensin System - drug effects Risk analysis Risk factors Rodents Stein-Leventhal syndrome |
| title | Effect of GLP-1 Receptor Agonists in the Cardiometabolic Complications in a Rat Model of Postmenopausal PCOS |
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