Estrogens Protect against High-Fat Diet-Induced Insulin Resistance and Glucose Intolerance in Mice
Although corroborating data indicate that estrogens influence glucose metabolism through the activation of the estrogen receptor α (ERα), it has not been established whether this pathway could represent an effective therapeutic target to fight against metabolic disturbances induced by a high-fat die...
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| description | Although corroborating data indicate that estrogens influence glucose metabolism through the activation of the estrogen receptor α (ERα), it has not been established whether this pathway could represent an effective therapeutic target to fight against metabolic disturbances induced by a high-fat diet (HFD). To this end, we first evaluated the influence of chronic 17β-estradiol (E2) administration in wild-type ovariectomized mice submitted to either a normal chow diet or a HFD. Whereas only a modest effect was observed in normal chow diet-fed mice, E2 administration exerted a protective effect against HFD-induced glucose intolerance, and this beneficial action was abolished in ERα-deficient mice. Furthermore, E2 treatment reduced HFD-induced insulin resistance by 50% during hyperinsulinemic euglycemic clamp studies and improved insulin signaling (Akt phosphorylation) in insulin-stimulated skeletal muscles. Unexpectedly, we found that E2 treatment enhanced cytokine (IL-6, TNF-α) and plasminogen activator inhibitor-1 mRNA expression induced by HFD in the liver and visceral adipose tissue. Interestingly, although the proinflammatory effect of E2 was abolished in visceral adipose tissue from chimeric mice grafted with bone marrow cells from ERα-deficient mice, the beneficial effect of the hormone on glucose tolerance was not altered, suggesting that the metabolic and inflammatory effects of estrogens can be dissociated. Eventually comparison of sham-operated with ovariectomized HFD-fed mice demonstrated that endogenous estrogens levels are sufficient to exert a full protective effect against insulin resistance and glucose intolerance. In conclusion, the regulation of the ERα pathway could represent an effective strategy to reduce the impact of high-fat diet-induced type 2 diabetes.
Despite a significant pro-inflammatory effect, estrogens protect from the occurrence of high-fat diet-induced insulin resistance and glucose intolerance through the activation of estrogen receptor α. |
| doi_str_mv | 10.1210/en.2008-0971 |
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Despite a significant pro-inflammatory effect, estrogens protect from the occurrence of high-fat diet-induced insulin resistance and glucose intolerance through the activation of estrogen receptor α.</description><identifier>ISSN: 0013-7227</identifier><identifier>EISSN: 1945-7170</identifier><identifier>DOI: 10.1210/en.2008-0971</identifier><identifier>PMID: 19164473</identifier><identifier>CODEN: ENDOAO</identifier><language>eng</language><publisher>Chevy Chase, MD: Endocrine Society</publisher><subject>17β-Estradiol ; Adipose tissue ; AKT protein ; Animals ; Biological and medical sciences ; Body fat ; Bone marrow ; Bone Marrow Cells ; Bone Marrow Cells - drug effects ; Bone Marrow Cells - metabolism ; Corrosion resistance ; Cytoprotection ; Cytoprotection - drug effects ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 2 ; Diabetes Mellitus, Type 2 - genetics ; Diabetes Mellitus, Type 2 - metabolism ; Diabetes. Impaired glucose tolerance ; Diet ; Diet, Atherogenic ; Dietary Fats ; Dietary Fats - pharmacology ; Drug Evaluation, Preclinical ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Estradiol ; Estradiol - administration & dosage ; Estradiol - pharmacology ; Estrogen Receptor alpha ; Estrogen Receptor alpha - genetics ; Estrogen Receptor alpha - physiology ; Estrogen receptors ; Estrogens ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; Fat metabolism ; Female ; Fundamental and applied biological sciences. Psychology ; Gene expression ; Glucose ; Glucose Intolerance ; Glucose Intolerance - etiology ; Glucose Intolerance - prevention & control ; Glucose metabolism ; Glucose tolerance ; Hepatocytes ; High fat diet ; Inflammation Mediators ; Inflammation Mediators - blood ; Inflammation Mediators - metabolism ; Insulin ; Insulin - metabolism ; Insulin Resistance ; Insulin Resistance - physiology ; Intolerance ; Medical sciences ; Metabolic rate ; Metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Muscle, Skeletal ; Muscle, Skeletal - drug effects ; Muscle, Skeletal - metabolism ; Muscles ; Ovariectomy ; Phosphorylation ; Plasminogen activator inhibitors ; Sex hormones ; Signal Transduction ; Signal Transduction - drug effects ; Skeletal muscle ; Therapeutic targets ; Tumor necrosis factor-α ; Vertebrates: endocrinology</subject><ispartof>Endocrinology (Philadelphia), 2009-05, Vol.150 (5), p.2109-2117</ispartof><rights>Copyright © 2009 by The Endocrine Society 2009</rights><rights>2009 INIST-CNRS</rights><rights>Copyright © 2009 by The Endocrine Society</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-73071a23fe180b8aee9d4ece59603353802d56c93721101cf791cbca09fb09483</citedby><cites>FETCH-LOGICAL-c526t-73071a23fe180b8aee9d4ece59603353802d56c93721101cf791cbca09fb09483</cites><orcidid>0000-0002-5362-3813</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21453229$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19164473$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://inserm.hal.science/inserm-00410271$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Riant, Elodie</creatorcontrib><creatorcontrib>Waget, Aurélie</creatorcontrib><creatorcontrib>Cogo, Haude</creatorcontrib><creatorcontrib>Arnal, Jean-François</creatorcontrib><creatorcontrib>Burcelin, Rémy</creatorcontrib><creatorcontrib>Gourdy, Pierre</creatorcontrib><title>Estrogens Protect against High-Fat Diet-Induced Insulin Resistance and Glucose Intolerance in Mice</title><title>Endocrinology (Philadelphia)</title><addtitle>Endocrinology</addtitle><description>Although corroborating data indicate that estrogens influence glucose metabolism through the activation of the estrogen receptor α (ERα), it has not been established whether this pathway could represent an effective therapeutic target to fight against metabolic disturbances induced by a high-fat diet (HFD). To this end, we first evaluated the influence of chronic 17β-estradiol (E2) administration in wild-type ovariectomized mice submitted to either a normal chow diet or a HFD. Whereas only a modest effect was observed in normal chow diet-fed mice, E2 administration exerted a protective effect against HFD-induced glucose intolerance, and this beneficial action was abolished in ERα-deficient mice. Furthermore, E2 treatment reduced HFD-induced insulin resistance by 50% during hyperinsulinemic euglycemic clamp studies and improved insulin signaling (Akt phosphorylation) in insulin-stimulated skeletal muscles. Unexpectedly, we found that E2 treatment enhanced cytokine (IL-6, TNF-α) and plasminogen activator inhibitor-1 mRNA expression induced by HFD in the liver and visceral adipose tissue. Interestingly, although the proinflammatory effect of E2 was abolished in visceral adipose tissue from chimeric mice grafted with bone marrow cells from ERα-deficient mice, the beneficial effect of the hormone on glucose tolerance was not altered, suggesting that the metabolic and inflammatory effects of estrogens can be dissociated. Eventually comparison of sham-operated with ovariectomized HFD-fed mice demonstrated that endogenous estrogens levels are sufficient to exert a full protective effect against insulin resistance and glucose intolerance. In conclusion, the regulation of the ERα pathway could represent an effective strategy to reduce the impact of high-fat diet-induced type 2 diabetes.
Despite a significant pro-inflammatory effect, estrogens protect from the occurrence of high-fat diet-induced insulin resistance and glucose intolerance through the activation of estrogen receptor α.</description><subject>17β-Estradiol</subject><subject>Adipose tissue</subject><subject>AKT protein</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Body fat</subject><subject>Bone marrow</subject><subject>Bone Marrow Cells</subject><subject>Bone Marrow Cells - drug effects</subject><subject>Bone Marrow Cells - metabolism</subject><subject>Corrosion resistance</subject><subject>Cytoprotection</subject><subject>Cytoprotection - drug effects</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Diabetes Mellitus, Type 2</subject><subject>Diabetes Mellitus, Type 2 - genetics</subject><subject>Diabetes Mellitus, Type 2 - metabolism</subject><subject>Diabetes. Impaired glucose tolerance</subject><subject>Diet</subject><subject>Diet, Atherogenic</subject><subject>Dietary Fats</subject><subject>Dietary Fats - pharmacology</subject><subject>Drug Evaluation, Preclinical</subject><subject>Endocrine pancreas. Apud cells (diseases)</subject><subject>Endocrinopathies</subject><subject>Estradiol</subject><subject>Estradiol - administration & dosage</subject><subject>Estradiol - pharmacology</subject><subject>Estrogen Receptor alpha</subject><subject>Estrogen Receptor alpha - genetics</subject><subject>Estrogen Receptor alpha - physiology</subject><subject>Estrogen receptors</subject><subject>Estrogens</subject><subject>Etiopathogenesis. Screening. Investigations. Target tissue resistance</subject><subject>Fat metabolism</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene expression</subject><subject>Glucose</subject><subject>Glucose Intolerance</subject><subject>Glucose Intolerance - etiology</subject><subject>Glucose Intolerance - prevention & control</subject><subject>Glucose metabolism</subject><subject>Glucose tolerance</subject><subject>Hepatocytes</subject><subject>High fat diet</subject><subject>Inflammation Mediators</subject><subject>Inflammation Mediators - blood</subject><subject>Inflammation Mediators - metabolism</subject><subject>Insulin</subject><subject>Insulin - metabolism</subject><subject>Insulin Resistance</subject><subject>Insulin Resistance - physiology</subject><subject>Intolerance</subject><subject>Medical sciences</subject><subject>Metabolic rate</subject><subject>Metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Muscle, Skeletal</subject><subject>Muscle, Skeletal - drug effects</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Muscles</subject><subject>Ovariectomy</subject><subject>Phosphorylation</subject><subject>Plasminogen activator inhibitors</subject><subject>Sex hormones</subject><subject>Signal Transduction</subject><subject>Signal Transduction - drug effects</subject><subject>Skeletal muscle</subject><subject>Therapeutic targets</subject><subject>Tumor necrosis factor-α</subject><subject>Vertebrates: endocrinology</subject><issn>0013-7227</issn><issn>1945-7170</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kVGL1DAUhYso7rj65rMURH2x671J2jSPy7q7MzCiiD6HNL2dzdJJxqQV_Pe2TtkB0aeQ3I97zsnJspcIF8gQPpC_YAB1AUrio2yFSpSFRAmPsxUA8kIyJs-yZyndT1chBH-anaHCSgjJV1lznYYYduRT_iWGgeyQm51xPg352u3uihsz5B8dDcXGt6OlNt_4NPbO518puTQYbyk3vs1v-9GGRNN4CD3FP-8T9clZep496Uyf6MVynmffb66_Xa2L7efbzdXltrAlq4ZCcpBoGO8Ia2hqQ6RaQZZKVQHnJa-BtWVlFZcMEdB2UqFtrAHVNaBEzc-z98e9d6bXh-j2Jv7SwTi9vtzqKRHFvQYQCEziT5zwt0f8EMOPkdKg9y5Z6nvjKYxJVxJLJkBN4Ou_wPswRj9F0Rw5lEpyxk7qNoaUInUPFhD0XJQmr-ei9FzUhL9alo7NntoTvDQzAW8WwCRr-m7-UpceOIainGRnd--OXBgP_5MsFkl-JMm3wUbn6RAppVOafxr9DfE3tZY</recordid><startdate>20090501</startdate><enddate>20090501</enddate><creator>Riant, Elodie</creator><creator>Waget, Aurélie</creator><creator>Cogo, Haude</creator><creator>Arnal, Jean-François</creator><creator>Burcelin, Rémy</creator><creator>Gourdy, Pierre</creator><general>Endocrine Society</general><general>Oxford University Press</general><scope>IQODW</scope><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>1XC</scope><orcidid>https://orcid.org/0000-0002-5362-3813</orcidid></search><sort><creationdate>20090501</creationdate><title>Estrogens Protect against High-Fat Diet-Induced Insulin Resistance and Glucose Intolerance in Mice</title><author>Riant, Elodie ; Waget, Aurélie ; Cogo, Haude ; Arnal, Jean-François ; Burcelin, Rémy ; Gourdy, Pierre</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-73071a23fe180b8aee9d4ece59603353802d56c93721101cf791cbca09fb09483</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>17β-Estradiol</topic><topic>Adipose tissue</topic><topic>AKT protein</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Body fat</topic><topic>Bone marrow</topic><topic>Bone Marrow Cells</topic><topic>Bone Marrow Cells - drug effects</topic><topic>Bone Marrow Cells - metabolism</topic><topic>Corrosion resistance</topic><topic>Cytoprotection</topic><topic>Cytoprotection - drug effects</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>Diabetes Mellitus, Type 2</topic><topic>Diabetes Mellitus, Type 2 - genetics</topic><topic>Diabetes Mellitus, Type 2 - metabolism</topic><topic>Diabetes. Impaired glucose tolerance</topic><topic>Diet</topic><topic>Diet, Atherogenic</topic><topic>Dietary Fats</topic><topic>Dietary Fats - pharmacology</topic><topic>Drug Evaluation, Preclinical</topic><topic>Endocrine pancreas. Apud cells (diseases)</topic><topic>Endocrinopathies</topic><topic>Estradiol</topic><topic>Estradiol - administration & dosage</topic><topic>Estradiol - pharmacology</topic><topic>Estrogen Receptor alpha</topic><topic>Estrogen Receptor alpha - genetics</topic><topic>Estrogen Receptor alpha - physiology</topic><topic>Estrogen receptors</topic><topic>Estrogens</topic><topic>Etiopathogenesis. Screening. Investigations. Target tissue resistance</topic><topic>Fat metabolism</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene expression</topic><topic>Glucose</topic><topic>Glucose Intolerance</topic><topic>Glucose Intolerance - etiology</topic><topic>Glucose Intolerance - prevention & control</topic><topic>Glucose metabolism</topic><topic>Glucose tolerance</topic><topic>Hepatocytes</topic><topic>High fat diet</topic><topic>Inflammation Mediators</topic><topic>Inflammation Mediators - blood</topic><topic>Inflammation Mediators - metabolism</topic><topic>Insulin</topic><topic>Insulin - metabolism</topic><topic>Insulin Resistance</topic><topic>Insulin Resistance - physiology</topic><topic>Intolerance</topic><topic>Medical sciences</topic><topic>Metabolic rate</topic><topic>Metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Muscle, Skeletal</topic><topic>Muscle, Skeletal - drug effects</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Muscles</topic><topic>Ovariectomy</topic><topic>Phosphorylation</topic><topic>Plasminogen activator inhibitors</topic><topic>Sex hormones</topic><topic>Signal Transduction</topic><topic>Signal Transduction - drug effects</topic><topic>Skeletal muscle</topic><topic>Therapeutic targets</topic><topic>Tumor necrosis factor-α</topic><topic>Vertebrates: endocrinology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Riant, Elodie</creatorcontrib><creatorcontrib>Waget, Aurélie</creatorcontrib><creatorcontrib>Cogo, Haude</creatorcontrib><creatorcontrib>Arnal, Jean-François</creatorcontrib><creatorcontrib>Burcelin, Rémy</creatorcontrib><creatorcontrib>Gourdy, Pierre</creatorcontrib><collection>Pascal-Francis</collection><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>Hyper Article en Ligne (HAL)</collection><jtitle>Endocrinology (Philadelphia)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Riant, Elodie</au><au>Waget, Aurélie</au><au>Cogo, Haude</au><au>Arnal, Jean-François</au><au>Burcelin, Rémy</au><au>Gourdy, Pierre</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Estrogens Protect against High-Fat Diet-Induced Insulin Resistance and Glucose Intolerance in Mice</atitle><jtitle>Endocrinology (Philadelphia)</jtitle><addtitle>Endocrinology</addtitle><date>2009-05-01</date><risdate>2009</risdate><volume>150</volume><issue>5</issue><spage>2109</spage><epage>2117</epage><pages>2109-2117</pages><issn>0013-7227</issn><eissn>1945-7170</eissn><coden>ENDOAO</coden><abstract>Although corroborating data indicate that estrogens influence glucose metabolism through the activation of the estrogen receptor α (ERα), it has not been established whether this pathway could represent an effective therapeutic target to fight against metabolic disturbances induced by a high-fat diet (HFD). To this end, we first evaluated the influence of chronic 17β-estradiol (E2) administration in wild-type ovariectomized mice submitted to either a normal chow diet or a HFD. Whereas only a modest effect was observed in normal chow diet-fed mice, E2 administration exerted a protective effect against HFD-induced glucose intolerance, and this beneficial action was abolished in ERα-deficient mice. Furthermore, E2 treatment reduced HFD-induced insulin resistance by 50% during hyperinsulinemic euglycemic clamp studies and improved insulin signaling (Akt phosphorylation) in insulin-stimulated skeletal muscles. Unexpectedly, we found that E2 treatment enhanced cytokine (IL-6, TNF-α) and plasminogen activator inhibitor-1 mRNA expression induced by HFD in the liver and visceral adipose tissue. Interestingly, although the proinflammatory effect of E2 was abolished in visceral adipose tissue from chimeric mice grafted with bone marrow cells from ERα-deficient mice, the beneficial effect of the hormone on glucose tolerance was not altered, suggesting that the metabolic and inflammatory effects of estrogens can be dissociated. Eventually comparison of sham-operated with ovariectomized HFD-fed mice demonstrated that endogenous estrogens levels are sufficient to exert a full protective effect against insulin resistance and glucose intolerance. In conclusion, the regulation of the ERα pathway could represent an effective strategy to reduce the impact of high-fat diet-induced type 2 diabetes.
Despite a significant pro-inflammatory effect, estrogens protect from the occurrence of high-fat diet-induced insulin resistance and glucose intolerance through the activation of estrogen receptor α.</abstract><cop>Chevy Chase, MD</cop><pub>Endocrine Society</pub><pmid>19164473</pmid><doi>10.1210/en.2008-0971</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-5362-3813</orcidid></addata></record> |
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| issn | 0013-7227 1945-7170 |
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| recordid | cdi_hal_primary_oai_HAL_inserm_00410271v1 |
| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | 17β-Estradiol Adipose tissue AKT protein Animals Biological and medical sciences Body fat Bone marrow Bone Marrow Cells Bone Marrow Cells - drug effects Bone Marrow Cells - metabolism Corrosion resistance Cytoprotection Cytoprotection - drug effects Diabetes mellitus (non-insulin dependent) Diabetes Mellitus, Type 2 Diabetes Mellitus, Type 2 - genetics Diabetes Mellitus, Type 2 - metabolism Diabetes. Impaired glucose tolerance Diet Diet, Atherogenic Dietary Fats Dietary Fats - pharmacology Drug Evaluation, Preclinical Endocrine pancreas. Apud cells (diseases) Endocrinopathies Estradiol Estradiol - administration & dosage Estradiol - pharmacology Estrogen Receptor alpha Estrogen Receptor alpha - genetics Estrogen Receptor alpha - physiology Estrogen receptors Estrogens Etiopathogenesis. Screening. Investigations. Target tissue resistance Fat metabolism Female Fundamental and applied biological sciences. Psychology Gene expression Glucose Glucose Intolerance Glucose Intolerance - etiology Glucose Intolerance - prevention & control Glucose metabolism Glucose tolerance Hepatocytes High fat diet Inflammation Mediators Inflammation Mediators - blood Inflammation Mediators - metabolism Insulin Insulin - metabolism Insulin Resistance Insulin Resistance - physiology Intolerance Medical sciences Metabolic rate Metabolism Mice Mice, Inbred C57BL Mice, Knockout Muscle, Skeletal Muscle, Skeletal - drug effects Muscle, Skeletal - metabolism Muscles Ovariectomy Phosphorylation Plasminogen activator inhibitors Sex hormones Signal Transduction Signal Transduction - drug effects Skeletal muscle Therapeutic targets Tumor necrosis factor-α Vertebrates: endocrinology |
| title | Estrogens Protect against High-Fat Diet-Induced Insulin Resistance and Glucose Intolerance in Mice |
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