Loss of FXR Protects against Diet-Induced Obesity and Accelerates Liver Carcinogenesis in ob/ob Mice
Farnesoid X receptor (FXR) is known to play important regulatory roles in bile acid, lipid, and carbohydrate metabolism. Aged (>12 months old) Fxr−/− mice also develop spontaneous liver carcinomas. In this report, we used three mouse models to investigate the role of FXR deficiency in obesity. As...
Gespeichert in:
| Veröffentlicht in: | Molecular endocrinology (Baltimore, Md.) Md.), 2012-02, Vol.26 (2), p.272-280 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 280 |
|---|---|
| container_issue | 2 |
| container_start_page | 272 |
| container_title | Molecular endocrinology (Baltimore, Md.) |
| container_volume | 26 |
| creator | Zhang, Yanqiao Ge, Xuemei Heemstra, Lydia A Chen, Wei-Dong Xu, Jiesi Smith, Joseph L Ma, Huiyan Kasim, Neda Edwards, Peter A Novak, Colleen M |
| description | Farnesoid X receptor (FXR) is known to play important regulatory roles in bile acid, lipid, and carbohydrate metabolism. Aged (>12 months old) Fxr−/− mice also develop spontaneous liver carcinomas. In this report, we used three mouse models to investigate the role of FXR deficiency in obesity. As compared with low-density lipoprotein receptor (Ldlr) knockout (Ldlr−/−) mice, the Ldlr−/−Fxr−/− double-knockout mice were highly resistant to diet-induced obesity, which was associated with increased expression of genes involved in energy metabolism in the skeletal muscle and brown adipose tissue. Such a striking effect of FXR deficiency on obesity on an Ldlr−/− background led us to investigate whether FXR deficiency alone is sufficient to affect obesity. As compared with wild-type mice, Fxr−/− mice showed resistance to diet-induced weight gain. Interestingly, only female Fxr−/− mice showed significant resistance to diet-induced obesity, which was accompanied by increased energy expenditure in these mice. Finally, we determined the effect of FXR deficiency on obesity in a genetically obese and diabetic mouse model. We generated ob−/−Fxr−/− mice that were deficient in both Leptin and Fxr. On a chow diet, ob−/−Fxr−/− mice gained less body weight and had reduced body fat mass as compared with ob/ob mice. In addition, we observed liver carcinomas in 43% of young ( |
| doi_str_mv | 10.1210/me.2011-1157 |
| format | Article |
| fullrecord | <record><control><sourceid>oup_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3275160</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1210/me.2011-1157</oup_id><sourcerecordid>10.1210/me.2011-1157</sourcerecordid><originalsourceid>FETCH-LOGICAL-c525t-129e9408eaf064a1994d1975430bcc553e4af1c3bf96eb10bad7d915b76ec1853</originalsourceid><addsrcrecordid>eNp1kE1rGzEQQEVpaZy0t56Lbr1kE412tStdCsH5aMDFITSQm9DHrKtgS0ZaB_Lvs8ZOaCE56TBv3ohHyDdgJ8CBna7whDOACkB0H8gEVNNUSkH3kUyYlLKSkqkDcljKA2PQCAmfyQHnvAXJ2YT4WSqFpp5e3t_Sm5wGdEOhZmFCLAM9DzhU19FvHHo6t1jC8ERN9PTMOVxiNgMWOguPmOnUZBdiWmAcqUJDpMmeJkt_B4dfyKfeLAt-3b9H5O7y4s_0VzWbX11Pz2aVE1wMFXCFqmESTc_axoBSjQfViaZm1jkhamxMD662vWrRArPGd16BsF2LDqSoj8jPnXe9sSv0DuOQzVKvc1iZ_KSTCfr_SQx_9SI96pp3Alo2Co53ApfHLBn7111geltbr1Bva-tt7RH__u-9V_gl7wj82AFps35PVe1V9Y7E6JPLIeI6Yyn6IW1yHJu9_YFn2WmY5A</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Loss of FXR Protects against Diet-Induced Obesity and Accelerates Liver Carcinogenesis in ob/ob Mice</title><source>Oxford University Press Journals All Titles (1996-Current)</source><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><source>Journals@Ovid Complete</source><creator>Zhang, Yanqiao ; Ge, Xuemei ; Heemstra, Lydia A ; Chen, Wei-Dong ; Xu, Jiesi ; Smith, Joseph L ; Ma, Huiyan ; Kasim, Neda ; Edwards, Peter A ; Novak, Colleen M</creator><creatorcontrib>Zhang, Yanqiao ; Ge, Xuemei ; Heemstra, Lydia A ; Chen, Wei-Dong ; Xu, Jiesi ; Smith, Joseph L ; Ma, Huiyan ; Kasim, Neda ; Edwards, Peter A ; Novak, Colleen M</creatorcontrib><description>Farnesoid X receptor (FXR) is known to play important regulatory roles in bile acid, lipid, and carbohydrate metabolism. Aged (>12 months old) Fxr−/− mice also develop spontaneous liver carcinomas. In this report, we used three mouse models to investigate the role of FXR deficiency in obesity. As compared with low-density lipoprotein receptor (Ldlr) knockout (Ldlr−/−) mice, the Ldlr−/−Fxr−/− double-knockout mice were highly resistant to diet-induced obesity, which was associated with increased expression of genes involved in energy metabolism in the skeletal muscle and brown adipose tissue. Such a striking effect of FXR deficiency on obesity on an Ldlr−/− background led us to investigate whether FXR deficiency alone is sufficient to affect obesity. As compared with wild-type mice, Fxr−/− mice showed resistance to diet-induced weight gain. Interestingly, only female Fxr−/− mice showed significant resistance to diet-induced obesity, which was accompanied by increased energy expenditure in these mice. Finally, we determined the effect of FXR deficiency on obesity in a genetically obese and diabetic mouse model. We generated ob−/−Fxr−/− mice that were deficient in both Leptin and Fxr. On a chow diet, ob−/−Fxr−/− mice gained less body weight and had reduced body fat mass as compared with ob/ob mice. In addition, we observed liver carcinomas in 43% of young (<11 months old) Ob−/−Fxr−/− mice. Together these data indicate that loss of FXR prevents diet-induced or genetic obesity and accelerates liver carcinogenesis under diabetic conditions.</description><identifier>ISSN: 0888-8809</identifier><identifier>EISSN: 1944-9917</identifier><identifier>DOI: 10.1210/me.2011-1157</identifier><identifier>PMID: 22261820</identifier><language>eng</language><publisher>United States: Endocrine Society</publisher><subject>Adipose Tissue, Brown - pathology ; Adiposity - genetics ; Animals ; Carcinoma - etiology ; Carcinoma - genetics ; Cell Transformation, Neoplastic - genetics ; Diet, High-Fat - adverse effects ; Dietary Fats - metabolism ; Energy Metabolism - genetics ; Female ; Gene Knockout Techniques ; Glucose Intolerance - complications ; Glucose Intolerance - genetics ; Intestinal Absorption ; Leptin - deficiency ; Leptin - genetics ; Liver - pathology ; Liver Neoplasms - etiology ; Liver Neoplasms - genetics ; Male ; Mice ; Mice, Knockout ; Mice, Obese ; Muscle, Skeletal - metabolism ; Obesity - etiology ; Obesity - genetics ; Original Research ; Receptors, Cytoplasmic and Nuclear - deficiency ; Receptors, Cytoplasmic and Nuclear - genetics ; Sex Factors ; Weight Gain - genetics</subject><ispartof>Molecular endocrinology (Baltimore, Md.), 2012-02, Vol.26 (2), p.272-280</ispartof><rights>Copyright © 2012 by The Endocrine Society</rights><rights>Copyright © 2012 by The Endocrine Society 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c525t-129e9408eaf064a1994d1975430bcc553e4af1c3bf96eb10bad7d915b76ec1853</citedby><cites>FETCH-LOGICAL-c525t-129e9408eaf064a1994d1975430bcc553e4af1c3bf96eb10bad7d915b76ec1853</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22261820$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Yanqiao</creatorcontrib><creatorcontrib>Ge, Xuemei</creatorcontrib><creatorcontrib>Heemstra, Lydia A</creatorcontrib><creatorcontrib>Chen, Wei-Dong</creatorcontrib><creatorcontrib>Xu, Jiesi</creatorcontrib><creatorcontrib>Smith, Joseph L</creatorcontrib><creatorcontrib>Ma, Huiyan</creatorcontrib><creatorcontrib>Kasim, Neda</creatorcontrib><creatorcontrib>Edwards, Peter A</creatorcontrib><creatorcontrib>Novak, Colleen M</creatorcontrib><title>Loss of FXR Protects against Diet-Induced Obesity and Accelerates Liver Carcinogenesis in ob/ob Mice</title><title>Molecular endocrinology (Baltimore, Md.)</title><addtitle>Mol Endocrinol</addtitle><description>Farnesoid X receptor (FXR) is known to play important regulatory roles in bile acid, lipid, and carbohydrate metabolism. Aged (>12 months old) Fxr−/− mice also develop spontaneous liver carcinomas. In this report, we used three mouse models to investigate the role of FXR deficiency in obesity. As compared with low-density lipoprotein receptor (Ldlr) knockout (Ldlr−/−) mice, the Ldlr−/−Fxr−/− double-knockout mice were highly resistant to diet-induced obesity, which was associated with increased expression of genes involved in energy metabolism in the skeletal muscle and brown adipose tissue. Such a striking effect of FXR deficiency on obesity on an Ldlr−/− background led us to investigate whether FXR deficiency alone is sufficient to affect obesity. As compared with wild-type mice, Fxr−/− mice showed resistance to diet-induced weight gain. Interestingly, only female Fxr−/− mice showed significant resistance to diet-induced obesity, which was accompanied by increased energy expenditure in these mice. Finally, we determined the effect of FXR deficiency on obesity in a genetically obese and diabetic mouse model. We generated ob−/−Fxr−/− mice that were deficient in both Leptin and Fxr. On a chow diet, ob−/−Fxr−/− mice gained less body weight and had reduced body fat mass as compared with ob/ob mice. In addition, we observed liver carcinomas in 43% of young (<11 months old) Ob−/−Fxr−/− mice. Together these data indicate that loss of FXR prevents diet-induced or genetic obesity and accelerates liver carcinogenesis under diabetic conditions.</description><subject>Adipose Tissue, Brown - pathology</subject><subject>Adiposity - genetics</subject><subject>Animals</subject><subject>Carcinoma - etiology</subject><subject>Carcinoma - genetics</subject><subject>Cell Transformation, Neoplastic - genetics</subject><subject>Diet, High-Fat - adverse effects</subject><subject>Dietary Fats - metabolism</subject><subject>Energy Metabolism - genetics</subject><subject>Female</subject><subject>Gene Knockout Techniques</subject><subject>Glucose Intolerance - complications</subject><subject>Glucose Intolerance - genetics</subject><subject>Intestinal Absorption</subject><subject>Leptin - deficiency</subject><subject>Leptin - genetics</subject><subject>Liver - pathology</subject><subject>Liver Neoplasms - etiology</subject><subject>Liver Neoplasms - genetics</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Mice, Obese</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Obesity - etiology</subject><subject>Obesity - genetics</subject><subject>Original Research</subject><subject>Receptors, Cytoplasmic and Nuclear - deficiency</subject><subject>Receptors, Cytoplasmic and Nuclear - genetics</subject><subject>Sex Factors</subject><subject>Weight Gain - genetics</subject><issn>0888-8809</issn><issn>1944-9917</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kE1rGzEQQEVpaZy0t56Lbr1kE412tStdCsH5aMDFITSQm9DHrKtgS0ZaB_Lvs8ZOaCE56TBv3ohHyDdgJ8CBna7whDOACkB0H8gEVNNUSkH3kUyYlLKSkqkDcljKA2PQCAmfyQHnvAXJ2YT4WSqFpp5e3t_Sm5wGdEOhZmFCLAM9DzhU19FvHHo6t1jC8ERN9PTMOVxiNgMWOguPmOnUZBdiWmAcqUJDpMmeJkt_B4dfyKfeLAt-3b9H5O7y4s_0VzWbX11Pz2aVE1wMFXCFqmESTc_axoBSjQfViaZm1jkhamxMD662vWrRArPGd16BsF2LDqSoj8jPnXe9sSv0DuOQzVKvc1iZ_KSTCfr_SQx_9SI96pp3Alo2Co53ApfHLBn7111geltbr1Bva-tt7RH__u-9V_gl7wj82AFps35PVe1V9Y7E6JPLIeI6Yyn6IW1yHJu9_YFn2WmY5A</recordid><startdate>20120201</startdate><enddate>20120201</enddate><creator>Zhang, Yanqiao</creator><creator>Ge, Xuemei</creator><creator>Heemstra, Lydia A</creator><creator>Chen, Wei-Dong</creator><creator>Xu, Jiesi</creator><creator>Smith, Joseph L</creator><creator>Ma, Huiyan</creator><creator>Kasim, Neda</creator><creator>Edwards, Peter A</creator><creator>Novak, Colleen M</creator><general>Endocrine Society</general><general>Oxford University Press</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>5PM</scope></search><sort><creationdate>20120201</creationdate><title>Loss of FXR Protects against Diet-Induced Obesity and Accelerates Liver Carcinogenesis in ob/ob Mice</title><author>Zhang, Yanqiao ; Ge, Xuemei ; Heemstra, Lydia A ; Chen, Wei-Dong ; Xu, Jiesi ; Smith, Joseph L ; Ma, Huiyan ; Kasim, Neda ; Edwards, Peter A ; Novak, Colleen M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c525t-129e9408eaf064a1994d1975430bcc553e4af1c3bf96eb10bad7d915b76ec1853</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adipose Tissue, Brown - pathology</topic><topic>Adiposity - genetics</topic><topic>Animals</topic><topic>Carcinoma - etiology</topic><topic>Carcinoma - genetics</topic><topic>Cell Transformation, Neoplastic - genetics</topic><topic>Diet, High-Fat - adverse effects</topic><topic>Dietary Fats - metabolism</topic><topic>Energy Metabolism - genetics</topic><topic>Female</topic><topic>Gene Knockout Techniques</topic><topic>Glucose Intolerance - complications</topic><topic>Glucose Intolerance - genetics</topic><topic>Intestinal Absorption</topic><topic>Leptin - deficiency</topic><topic>Leptin - genetics</topic><topic>Liver - pathology</topic><topic>Liver Neoplasms - etiology</topic><topic>Liver Neoplasms - genetics</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Mice, Obese</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Obesity - etiology</topic><topic>Obesity - genetics</topic><topic>Original Research</topic><topic>Receptors, Cytoplasmic and Nuclear - deficiency</topic><topic>Receptors, Cytoplasmic and Nuclear - genetics</topic><topic>Sex Factors</topic><topic>Weight Gain - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Yanqiao</creatorcontrib><creatorcontrib>Ge, Xuemei</creatorcontrib><creatorcontrib>Heemstra, Lydia A</creatorcontrib><creatorcontrib>Chen, Wei-Dong</creatorcontrib><creatorcontrib>Xu, Jiesi</creatorcontrib><creatorcontrib>Smith, Joseph L</creatorcontrib><creatorcontrib>Ma, Huiyan</creatorcontrib><creatorcontrib>Kasim, Neda</creatorcontrib><creatorcontrib>Edwards, Peter A</creatorcontrib><creatorcontrib>Novak, Colleen M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular endocrinology (Baltimore, Md.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Yanqiao</au><au>Ge, Xuemei</au><au>Heemstra, Lydia A</au><au>Chen, Wei-Dong</au><au>Xu, Jiesi</au><au>Smith, Joseph L</au><au>Ma, Huiyan</au><au>Kasim, Neda</au><au>Edwards, Peter A</au><au>Novak, Colleen M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Loss of FXR Protects against Diet-Induced Obesity and Accelerates Liver Carcinogenesis in ob/ob Mice</atitle><jtitle>Molecular endocrinology (Baltimore, Md.)</jtitle><addtitle>Mol Endocrinol</addtitle><date>2012-02-01</date><risdate>2012</risdate><volume>26</volume><issue>2</issue><spage>272</spage><epage>280</epage><pages>272-280</pages><issn>0888-8809</issn><eissn>1944-9917</eissn><abstract>Farnesoid X receptor (FXR) is known to play important regulatory roles in bile acid, lipid, and carbohydrate metabolism. Aged (>12 months old) Fxr−/− mice also develop spontaneous liver carcinomas. In this report, we used three mouse models to investigate the role of FXR deficiency in obesity. As compared with low-density lipoprotein receptor (Ldlr) knockout (Ldlr−/−) mice, the Ldlr−/−Fxr−/− double-knockout mice were highly resistant to diet-induced obesity, which was associated with increased expression of genes involved in energy metabolism in the skeletal muscle and brown adipose tissue. Such a striking effect of FXR deficiency on obesity on an Ldlr−/− background led us to investigate whether FXR deficiency alone is sufficient to affect obesity. As compared with wild-type mice, Fxr−/− mice showed resistance to diet-induced weight gain. Interestingly, only female Fxr−/− mice showed significant resistance to diet-induced obesity, which was accompanied by increased energy expenditure in these mice. Finally, we determined the effect of FXR deficiency on obesity in a genetically obese and diabetic mouse model. We generated ob−/−Fxr−/− mice that were deficient in both Leptin and Fxr. On a chow diet, ob−/−Fxr−/− mice gained less body weight and had reduced body fat mass as compared with ob/ob mice. In addition, we observed liver carcinomas in 43% of young (<11 months old) Ob−/−Fxr−/− mice. Together these data indicate that loss of FXR prevents diet-induced or genetic obesity and accelerates liver carcinogenesis under diabetic conditions.</abstract><cop>United States</cop><pub>Endocrine Society</pub><pmid>22261820</pmid><doi>10.1210/me.2011-1157</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0888-8809 |
| ispartof | Molecular endocrinology (Baltimore, Md.), 2012-02, Vol.26 (2), p.272-280 |
| issn | 0888-8809 1944-9917 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3275160 |
| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection; Journals@Ovid Complete |
| subjects | Adipose Tissue, Brown - pathology Adiposity - genetics Animals Carcinoma - etiology Carcinoma - genetics Cell Transformation, Neoplastic - genetics Diet, High-Fat - adverse effects Dietary Fats - metabolism Energy Metabolism - genetics Female Gene Knockout Techniques Glucose Intolerance - complications Glucose Intolerance - genetics Intestinal Absorption Leptin - deficiency Leptin - genetics Liver - pathology Liver Neoplasms - etiology Liver Neoplasms - genetics Male Mice Mice, Knockout Mice, Obese Muscle, Skeletal - metabolism Obesity - etiology Obesity - genetics Original Research Receptors, Cytoplasmic and Nuclear - deficiency Receptors, Cytoplasmic and Nuclear - genetics Sex Factors Weight Gain - genetics |
| title | Loss of FXR Protects against Diet-Induced Obesity and Accelerates Liver Carcinogenesis in ob/ob Mice |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T01%3A43%3A31IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-oup_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Loss%20of%20FXR%20Protects%20against%20Diet-Induced%20Obesity%20and%20Accelerates%20Liver%20Carcinogenesis%20in%20ob/ob%20Mice&rft.jtitle=Molecular%20endocrinology%20(Baltimore,%20Md.)&rft.au=Zhang,%20Yanqiao&rft.date=2012-02-01&rft.volume=26&rft.issue=2&rft.spage=272&rft.epage=280&rft.pages=272-280&rft.issn=0888-8809&rft.eissn=1944-9917&rft_id=info:doi/10.1210/me.2011-1157&rft_dat=%3Coup_pubme%3E10.1210/me.2011-1157%3C/oup_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/22261820&rft_oup_id=10.1210/me.2011-1157&rfr_iscdi=true |