Jorge F.A. Model , Rafaella S. Normann , Éverton L. Vogt , Maiza Von Dentz , Marjoriane de Amaral , Rui Xu , Tsvetan Bachvaroff , Poli Mara Spritzer , J. Sook Chung , Anapaula S. Vinagre
{"title":"胰高血糖素样肽 1（GLP-1）与雌激素之间的相互作用可调节脂质代谢。","authors":"Jorge F.A. Model , Rafaella S. Normann , Éverton L. Vogt , Maiza Von Dentz , Marjoriane de Amaral , Rui Xu , Tsvetan Bachvaroff , Poli Mara Spritzer , J. Sook Chung , Anapaula S. Vinagre","doi":"10.1016/j.bcp.2024.116623","DOIUrl":null,"url":null,"abstract":"<div><div>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.</div><div>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.</div><div>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.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"230 ","pages":"Article 116623"},"PeriodicalIF":5.3000,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Interactions between glucagon like peptide 1 (GLP-1) and estrogens regulates lipid metabolism\",\"authors\":\"Jorge F.A. Model , Rafaella S. Normann , Éverton L. Vogt , Maiza Von Dentz , Marjoriane de Amaral , Rui Xu , Tsvetan Bachvaroff , Poli Mara Spritzer , J. Sook Chung , Anapaula S. Vinagre\",\"doi\":\"10.1016/j.bcp.2024.116623\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>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.</div><div>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.</div><div>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.</div></div>\",\"PeriodicalId\":8806,\"journal\":{\"name\":\"Biochemical pharmacology\",\"volume\":\"230 \",\"pages\":\"Article 116623\"},\"PeriodicalIF\":5.3000,\"publicationDate\":\"2024-11-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biochemical pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0006295224006233\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochemical pharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0006295224006233","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Interactions between glucagon like peptide 1 (GLP-1) and estrogens regulates lipid metabolism
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.
期刊介绍：
Biochemical Pharmacology publishes original research findings, Commentaries and review articles related to the elucidation of cellular and tissue function(s) at the biochemical and molecular levels, the modification of cellular phenotype(s) by genetic, transcriptional/translational or drug/compound-induced modifications, as well as the pharmacodynamics and pharmacokinetics of xenobiotics and drugs, the latter including both small molecules and biologics.
The journal''s target audience includes scientists engaged in the identification and study of the mechanisms of action of xenobiotics, biologics and drugs and in the drug discovery and development process.
All areas of cellular biology and cellular, tissue/organ and whole animal pharmacology fall within the scope of the journal. Drug classes covered include anti-infectives, anti-inflammatory agents, chemotherapeutics, cardiovascular, endocrinological, immunological, metabolic, neurological and psychiatric drugs, as well as research on drug metabolism and kinetics. While medicinal chemistry is a topic of complimentary interest, manuscripts in this area must contain sufficient biological data to characterize pharmacologically the compounds reported. Submissions describing work focused predominately on chemical synthesis and molecular modeling will not be considered for review.
While particular emphasis is placed on reporting the results of molecular and biochemical studies, research involving the use of tissue and animal models of human pathophysiology and toxicology is of interest to the extent that it helps define drug mechanisms of action, safety and efficacy.
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