Interactions between glucagon like peptide 1 (GLP-1) and estrogens regulates lipid metabolism
[Display omitted] Obesity, characterized by excessive fat accumulation in white adipose tissue (WAT), is linked to numerous health issues, including insulin resistance (IR), and type 2 diabetes mellitus (DM2). The distribution of adipose tissue differs by sex, with men typically exhibiting android a...
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| Veröffentlicht in: | Biochemical pharmacology 2024-12, Vol.230 (Pt 3), p.116623, Article 116623 |
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| creator | Model, Jorge F.A. Normann, Rafaella S. Vogt, Éverton L. Dentz, Maiza Von de Amaral, Marjoriane Xu, Rui Bachvaroff, Tsvetan Spritzer, Poli Mara Chung, J. Sook Vinagre, Anapaula S. |
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Obesity, characterized by excessive fat accumulation in white adipose tissue (WAT), is linked to numerous health issues, including insulin resistance (IR), and type 2 diabetes mellitus (DM2). The distribution of adipose tissue differs by sex, with men typically exhibiting android adiposity and pre-menopausal women displaying gynecoid adiposity. After menopause, women have an increased risk of developing android-type obesity, IR, and DM2. Glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RAs) are important in treating obesity and DM2 by regulating insulin secretion, impacting glucose and lipid metabolism. GLP-1Rs are found in various tissues including the pancreas, brain, and adipose tissue. Studies suggest GLP-1RAs and estrogen replacement therapies have similar effects on tissues like the liver, central nervous system, and WAT, probably by converging pathways involving protein kinases.
To investigate these interactions, female rats underwent ovariectomy (OVR) to promote a state of estrogen deficiency. After 20 days, the rats were euthanized and the tissues were incubated with 10 μM of liraglutide, a GLP-1RA. Results showed significant changes in metabolic parameters: OVR increased lipid catabolism in perirenal WAT and basal lipolysis in subcutaneous WAT, while liraglutide treatment enhanced stimulated lipolysis in subcutaneous WAT. Liver responses included increased stimulated lipolysis with liraglutide. Transcriptome analysis revealed distinct gene expression patterns in WAT of OVR rats and those treated with GLP-1RA, highlighting pathways related to lipid and glucose metabolism. Functional enrichment analysis showed estrogen’s pivotal role in these pathways, influencing genes involved in lipid metabolism regulation.
Overall, the study underscores GLP-1RA acting directly on adipose tissues and highlights the complex interactions between GLP-1 and estrogen in regulating metabolism, suggesting potential synergistic therapeutic effects in treating metabolic disorders like obesity and DM2. |
| doi_str_mv | 10.1016/j.bcp.2024.116623 |
| format | Article |
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Obesity, characterized by excessive fat accumulation in white adipose tissue (WAT), is linked to numerous health issues, including insulin resistance (IR), and type 2 diabetes mellitus (DM2). The distribution of adipose tissue differs by sex, with men typically exhibiting android adiposity and pre-menopausal women displaying gynecoid adiposity. After menopause, women have an increased risk of developing android-type obesity, IR, and DM2. Glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RAs) are important in treating obesity and DM2 by regulating insulin secretion, impacting glucose and lipid metabolism. GLP-1Rs are found in various tissues including the pancreas, brain, and adipose tissue. Studies suggest GLP-1RAs and estrogen replacement therapies have similar effects on tissues like the liver, central nervous system, and WAT, probably by converging pathways involving protein kinases.
To investigate these interactions, female rats underwent ovariectomy (OVR) to promote a state of estrogen deficiency. After 20 days, the rats were euthanized and the tissues were incubated with 10 μM of liraglutide, a GLP-1RA. Results showed significant changes in metabolic parameters: OVR increased lipid catabolism in perirenal WAT and basal lipolysis in subcutaneous WAT, while liraglutide treatment enhanced stimulated lipolysis in subcutaneous WAT. Liver responses included increased stimulated lipolysis with liraglutide. Transcriptome analysis revealed distinct gene expression patterns in WAT of OVR rats and those treated with GLP-1RA, highlighting pathways related to lipid and glucose metabolism. Functional enrichment analysis showed estrogen’s pivotal role in these pathways, influencing genes involved in lipid metabolism regulation.
Overall, the study underscores GLP-1RA acting directly on adipose tissues and highlights the complex interactions between GLP-1 and estrogen in regulating metabolism, suggesting potential synergistic therapeutic effects in treating metabolic disorders like obesity and DM2.</description><identifier>ISSN: 0006-2952</identifier><identifier>ISSN: 1873-2968</identifier><identifier>EISSN: 1873-2968</identifier><identifier>DOI: 10.1016/j.bcp.2024.116623</identifier><identifier>PMID: 39542180</identifier><language>eng</language><publisher>England: Elsevier Inc</publisher><subject>Animals ; Estrogens ; Estrogens - metabolism ; Estrogens - pharmacology ; Female ; GLP-1 ; Glucagon-Like Peptide 1 - metabolism ; Incretins ; Lipid Metabolism - drug effects ; Lipid Metabolism - physiology ; Lipolysis - drug effects ; Liraglutide - pharmacology ; Menopause ; Ovariectomy ; Rats ; Rats, Sprague-Dawley</subject><ispartof>Biochemical pharmacology, 2024-12, Vol.230 (Pt 3), p.116623, Article 116623</ispartof><rights>2024 Elsevier Inc.</rights><rights>Copyright © 2024 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c235t-d6d26440651d92ba4609e8caf98d8bbd4875576b2b2649eb9f8e2b0a3f2ffe233</cites><orcidid>0000-0003-4573-0499</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006295224006233$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39542180$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Model, Jorge F.A.</creatorcontrib><creatorcontrib>Normann, Rafaella S.</creatorcontrib><creatorcontrib>Vogt, Éverton L.</creatorcontrib><creatorcontrib>Dentz, Maiza Von</creatorcontrib><creatorcontrib>de Amaral, Marjoriane</creatorcontrib><creatorcontrib>Xu, Rui</creatorcontrib><creatorcontrib>Bachvaroff, Tsvetan</creatorcontrib><creatorcontrib>Spritzer, Poli Mara</creatorcontrib><creatorcontrib>Chung, J. Sook</creatorcontrib><creatorcontrib>Vinagre, Anapaula S.</creatorcontrib><title>Interactions between glucagon like peptide 1 (GLP-1) and estrogens regulates lipid metabolism</title><title>Biochemical pharmacology</title><addtitle>Biochem Pharmacol</addtitle><description>[Display omitted]
Obesity, characterized by excessive fat accumulation in white adipose tissue (WAT), is linked to numerous health issues, including insulin resistance (IR), and type 2 diabetes mellitus (DM2). The distribution of adipose tissue differs by sex, with men typically exhibiting android adiposity and pre-menopausal women displaying gynecoid adiposity. After menopause, women have an increased risk of developing android-type obesity, IR, and DM2. Glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RAs) are important in treating obesity and DM2 by regulating insulin secretion, impacting glucose and lipid metabolism. GLP-1Rs are found in various tissues including the pancreas, brain, and adipose tissue. Studies suggest GLP-1RAs and estrogen replacement therapies have similar effects on tissues like the liver, central nervous system, and WAT, probably by converging pathways involving protein kinases.
To investigate these interactions, female rats underwent ovariectomy (OVR) to promote a state of estrogen deficiency. After 20 days, the rats were euthanized and the tissues were incubated with 10 μM of liraglutide, a GLP-1RA. Results showed significant changes in metabolic parameters: OVR increased lipid catabolism in perirenal WAT and basal lipolysis in subcutaneous WAT, while liraglutide treatment enhanced stimulated lipolysis in subcutaneous WAT. Liver responses included increased stimulated lipolysis with liraglutide. Transcriptome analysis revealed distinct gene expression patterns in WAT of OVR rats and those treated with GLP-1RA, highlighting pathways related to lipid and glucose metabolism. Functional enrichment analysis showed estrogen’s pivotal role in these pathways, influencing genes involved in lipid metabolism regulation.
Overall, the study underscores GLP-1RA acting directly on adipose tissues and highlights the complex interactions between GLP-1 and estrogen in regulating metabolism, suggesting potential synergistic therapeutic effects in treating metabolic disorders like obesity and DM2.</description><subject>Animals</subject><subject>Estrogens</subject><subject>Estrogens - metabolism</subject><subject>Estrogens - pharmacology</subject><subject>Female</subject><subject>GLP-1</subject><subject>Glucagon-Like Peptide 1 - metabolism</subject><subject>Incretins</subject><subject>Lipid Metabolism - drug effects</subject><subject>Lipid Metabolism - physiology</subject><subject>Lipolysis - drug effects</subject><subject>Liraglutide - pharmacology</subject><subject>Menopause</subject><subject>Ovariectomy</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><issn>0006-2952</issn><issn>1873-2968</issn><issn>1873-2968</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEtrGzEURkVJqF23P6CboKW7GEePGVlDVsG0qcGQLJJlEHrcMXLnFUnTkH9fGTtdZqUrON_HvQeh75SsKKHi-rAydlwxwsoVpUIw_gnNqVzzgtVCXqA5IUTkuWIz9CXGw_ErBf2MZryuSkYlmaPnbZ8gaJv80EdsIL0C9HjfTlbvhx63_g_gEcbkHWCKl3e7h4L-wLp3GGIKwx5yKsB-anWCmPHRO9xB0mZofey-ostGtxG-nd8Fevr183Hzu9jd3203t7vCMl6lwgnHRFkSUVFXM6NLQWqQVje1dNIYV8p1Va2FYSZjNZi6kcAM0bxhTQOM8wVannrHMLxMeTPV-WihbXUPwxQVp0xKJignGaUn1IYhxgCNGoPvdHhTlKijVXVQ2ao6WlUnqzlzda6fTAfuf-JdYwZuTgDkI_96CCpaD70F5wPYpNzgP6j_B6tgh04</recordid><startdate>202412</startdate><enddate>202412</enddate><creator>Model, Jorge F.A.</creator><creator>Normann, Rafaella S.</creator><creator>Vogt, Éverton L.</creator><creator>Dentz, Maiza Von</creator><creator>de Amaral, Marjoriane</creator><creator>Xu, Rui</creator><creator>Bachvaroff, Tsvetan</creator><creator>Spritzer, Poli Mara</creator><creator>Chung, J. Sook</creator><creator>Vinagre, Anapaula S.</creator><general>Elsevier Inc</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/0000-0003-4573-0499</orcidid></search><sort><creationdate>202412</creationdate><title>Interactions between glucagon like peptide 1 (GLP-1) and estrogens regulates lipid metabolism</title><author>Model, Jorge F.A. ; Normann, Rafaella S. ; Vogt, Éverton L. ; Dentz, Maiza Von ; de Amaral, Marjoriane ; Xu, Rui ; Bachvaroff, Tsvetan ; Spritzer, Poli Mara ; Chung, J. Sook ; Vinagre, Anapaula S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c235t-d6d26440651d92ba4609e8caf98d8bbd4875576b2b2649eb9f8e2b0a3f2ffe233</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Animals</topic><topic>Estrogens</topic><topic>Estrogens - metabolism</topic><topic>Estrogens - pharmacology</topic><topic>Female</topic><topic>GLP-1</topic><topic>Glucagon-Like Peptide 1 - metabolism</topic><topic>Incretins</topic><topic>Lipid Metabolism - drug effects</topic><topic>Lipid Metabolism - physiology</topic><topic>Lipolysis - drug effects</topic><topic>Liraglutide - pharmacology</topic><topic>Menopause</topic><topic>Ovariectomy</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Model, Jorge F.A.</creatorcontrib><creatorcontrib>Normann, Rafaella S.</creatorcontrib><creatorcontrib>Vogt, Éverton L.</creatorcontrib><creatorcontrib>Dentz, Maiza Von</creatorcontrib><creatorcontrib>de Amaral, Marjoriane</creatorcontrib><creatorcontrib>Xu, Rui</creatorcontrib><creatorcontrib>Bachvaroff, Tsvetan</creatorcontrib><creatorcontrib>Spritzer, Poli Mara</creatorcontrib><creatorcontrib>Chung, J. Sook</creatorcontrib><creatorcontrib>Vinagre, Anapaula S.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Model, Jorge F.A.</au><au>Normann, Rafaella S.</au><au>Vogt, Éverton L.</au><au>Dentz, Maiza Von</au><au>de Amaral, Marjoriane</au><au>Xu, Rui</au><au>Bachvaroff, Tsvetan</au><au>Spritzer, Poli Mara</au><au>Chung, J. Sook</au><au>Vinagre, Anapaula S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interactions between glucagon like peptide 1 (GLP-1) and estrogens regulates lipid metabolism</atitle><jtitle>Biochemical pharmacology</jtitle><addtitle>Biochem Pharmacol</addtitle><date>2024-12</date><risdate>2024</risdate><volume>230</volume><issue>Pt 3</issue><spage>116623</spage><pages>116623-</pages><artnum>116623</artnum><issn>0006-2952</issn><issn>1873-2968</issn><eissn>1873-2968</eissn><abstract>[Display omitted]
Obesity, characterized by excessive fat accumulation in white adipose tissue (WAT), is linked to numerous health issues, including insulin resistance (IR), and type 2 diabetes mellitus (DM2). The distribution of adipose tissue differs by sex, with men typically exhibiting android adiposity and pre-menopausal women displaying gynecoid adiposity. After menopause, women have an increased risk of developing android-type obesity, IR, and DM2. Glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RAs) are important in treating obesity and DM2 by regulating insulin secretion, impacting glucose and lipid metabolism. GLP-1Rs are found in various tissues including the pancreas, brain, and adipose tissue. Studies suggest GLP-1RAs and estrogen replacement therapies have similar effects on tissues like the liver, central nervous system, and WAT, probably by converging pathways involving protein kinases.
To investigate these interactions, female rats underwent ovariectomy (OVR) to promote a state of estrogen deficiency. After 20 days, the rats were euthanized and the tissues were incubated with 10 μM of liraglutide, a GLP-1RA. Results showed significant changes in metabolic parameters: OVR increased lipid catabolism in perirenal WAT and basal lipolysis in subcutaneous WAT, while liraglutide treatment enhanced stimulated lipolysis in subcutaneous WAT. Liver responses included increased stimulated lipolysis with liraglutide. Transcriptome analysis revealed distinct gene expression patterns in WAT of OVR rats and those treated with GLP-1RA, highlighting pathways related to lipid and glucose metabolism. Functional enrichment analysis showed estrogen’s pivotal role in these pathways, influencing genes involved in lipid metabolism regulation.
Overall, the study underscores GLP-1RA acting directly on adipose tissues and highlights the complex interactions between GLP-1 and estrogen in regulating metabolism, suggesting potential synergistic therapeutic effects in treating metabolic disorders like obesity and DM2.</abstract><cop>England</cop><pub>Elsevier Inc</pub><pmid>39542180</pmid><doi>10.1016/j.bcp.2024.116623</doi><orcidid>https://orcid.org/0000-0003-4573-0499</orcidid></addata></record> |
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| subjects | Animals Estrogens Estrogens - metabolism Estrogens - pharmacology Female GLP-1 Glucagon-Like Peptide 1 - metabolism Incretins Lipid Metabolism - drug effects Lipid Metabolism - physiology Lipolysis - drug effects Liraglutide - pharmacology Menopause Ovariectomy Rats Rats, Sprague-Dawley |
| title | Interactions between glucagon like peptide 1 (GLP-1) and estrogens regulates lipid metabolism |
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