Adipocyte-specific deficiency of Nfe2l1 disrupts plasticity of white adipose tissues and metabolic homeostasis in mice
The maintenance of healthy adipose tissues is essential for efficient regulation of energy homeostasis. Nuclear factor-erythroid 2-related factor 1 (NFE2L1, also known as Nrf1), a CNC-bZIP protein, is a master regulator of the cellular adaptive response to stresses. To investigate the role of NFE2L1...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2018-09, Vol.503 (1), p.264-270 |
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| creator | Hou, Yongyong Liu, Zhiyuan Zuo, Zhuo Gao, Tianchang Fu, Jingqi Wang, Huihui Xu, Yuanyuan Liu, Dianxin Yamamoto, Masayuki Zhu, Beibei Zhang, Yiguo Andersen, Melvin E. Zhang, Qiang Pi, Jingbo |
| description | The maintenance of healthy adipose tissues is essential for efficient regulation of energy homeostasis. Nuclear factor-erythroid 2-related factor 1 (NFE2L1, also known as Nrf1), a CNC-bZIP protein, is a master regulator of the cellular adaptive response to stresses. To investigate the role of NFE2L1 in adipocytes, we bred a line of mice with adipocyte-specific Nfe2l1 knockout (Nfe2l1(f)-KO), and found that Nfe2l1(f)-KO mice exhibited a dramatically reduced subcutaneous adipose tissue (SAT) mass, insulin resistance, adipocyte hypertrophy, and severe adipose inflammation. Mechanistic studies revealed that Nfe2l1 deficiency may disturb the expression of lipolytic genes in adipocytes, leading to adipocyte hypertrophy followed by inflammation, pyroptosis, and insulin resistance. Our findings reveal a novel role for NFE2L1 in regulating adipose tissue plasticity and energy homeostasis.
•Nfe2l1(f)-KO mice exhibit diminished subcutaneous adipose tissues.•Nfe2l1(f)-KO mice show severe adipocyte hypertrophy and adipose inflammation.•Nfe2l1(f)-KO mice develop glucose intolerance and insulin resistance. |
| doi_str_mv | 10.1016/j.bbrc.2018.06.013 |
| format | Article |
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•Nfe2l1(f)-KO mice exhibit diminished subcutaneous adipose tissues.•Nfe2l1(f)-KO mice show severe adipocyte hypertrophy and adipose inflammation.•Nfe2l1(f)-KO mice develop glucose intolerance and insulin resistance.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2018.06.013</identifier><identifier>PMID: 29935181</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; Adipocytes - metabolism ; Adipocytes - pathology ; Adipose ; ADIPOSE TISSUE ; Adipose Tissue, White - cytology ; Adipose Tissue, White - metabolism ; Adipose Tissue, White - pathology ; Adiposity ; Animals ; Body Fat Distribution ; Energy Metabolism ; Gene Expression Regulation ; GLUCOSE ; HOMEOSTASIS ; Hypertrophy ; INFLAMMATION ; Inflammation - genetics ; Inflammation - metabolism ; Inflammation - pathology ; INSULIN ; Insulin Resistance ; Lipolysis ; Male ; MICE ; Mice, Knockout ; NF-E2-Related Factor 1 - genetics ; NFE2L1 ; Pyroptosis</subject><ispartof>Biochemical and biophysical research communications, 2018-09, Vol.503 (1), p.264-270</ispartof><rights>2018 Elsevier Inc.</rights><rights>Copyright © 2018 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c499t-49b3f56b70a5934ba5af84156e9cc2aa440f220f12abe161c79994c5253f86ed3</citedby><cites>FETCH-LOGICAL-c499t-49b3f56b70a5934ba5af84156e9cc2aa440f220f12abe161c79994c5253f86ed3</cites><orcidid>0000-0003-3871-428X ; 0000-0003-0227-8041 ; 0000-0003-2354-9453</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbrc.2018.06.013$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29935181$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/23105687$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Hou, Yongyong</creatorcontrib><creatorcontrib>Liu, Zhiyuan</creatorcontrib><creatorcontrib>Zuo, Zhuo</creatorcontrib><creatorcontrib>Gao, Tianchang</creatorcontrib><creatorcontrib>Fu, Jingqi</creatorcontrib><creatorcontrib>Wang, Huihui</creatorcontrib><creatorcontrib>Xu, Yuanyuan</creatorcontrib><creatorcontrib>Liu, Dianxin</creatorcontrib><creatorcontrib>Yamamoto, Masayuki</creatorcontrib><creatorcontrib>Zhu, Beibei</creatorcontrib><creatorcontrib>Zhang, Yiguo</creatorcontrib><creatorcontrib>Andersen, Melvin E.</creatorcontrib><creatorcontrib>Zhang, Qiang</creatorcontrib><creatorcontrib>Pi, Jingbo</creatorcontrib><title>Adipocyte-specific deficiency of Nfe2l1 disrupts plasticity of white adipose tissues and metabolic homeostasis in mice</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>The maintenance of healthy adipose tissues is essential for efficient regulation of energy homeostasis. Nuclear factor-erythroid 2-related factor 1 (NFE2L1, also known as Nrf1), a CNC-bZIP protein, is a master regulator of the cellular adaptive response to stresses. To investigate the role of NFE2L1 in adipocytes, we bred a line of mice with adipocyte-specific Nfe2l1 knockout (Nfe2l1(f)-KO), and found that Nfe2l1(f)-KO mice exhibited a dramatically reduced subcutaneous adipose tissue (SAT) mass, insulin resistance, adipocyte hypertrophy, and severe adipose inflammation. Mechanistic studies revealed that Nfe2l1 deficiency may disturb the expression of lipolytic genes in adipocytes, leading to adipocyte hypertrophy followed by inflammation, pyroptosis, and insulin resistance. Our findings reveal a novel role for NFE2L1 in regulating adipose tissue plasticity and energy homeostasis.
•Nfe2l1(f)-KO mice exhibit diminished subcutaneous adipose tissues.•Nfe2l1(f)-KO mice show severe adipocyte hypertrophy and adipose inflammation.•Nfe2l1(f)-KO mice develop glucose intolerance and insulin resistance.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>Adipocytes - metabolism</subject><subject>Adipocytes - pathology</subject><subject>Adipose</subject><subject>ADIPOSE TISSUE</subject><subject>Adipose Tissue, White - cytology</subject><subject>Adipose Tissue, White - metabolism</subject><subject>Adipose Tissue, White - pathology</subject><subject>Adiposity</subject><subject>Animals</subject><subject>Body Fat Distribution</subject><subject>Energy Metabolism</subject><subject>Gene Expression Regulation</subject><subject>GLUCOSE</subject><subject>HOMEOSTASIS</subject><subject>Hypertrophy</subject><subject>INFLAMMATION</subject><subject>Inflammation - genetics</subject><subject>Inflammation - metabolism</subject><subject>Inflammation - pathology</subject><subject>INSULIN</subject><subject>Insulin Resistance</subject><subject>Lipolysis</subject><subject>Male</subject><subject>MICE</subject><subject>Mice, Knockout</subject><subject>NF-E2-Related Factor 1 - genetics</subject><subject>NFE2L1</subject><subject>Pyroptosis</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kT2P1DAQhi0E4paDP0CBLNHQJMw4sTeWaE4nvqQTNCDRWY4z1nqVxCH2Htp_j8MelDR2Mc-8fuWHsZcINQKqt8e671dXC8CuBlUDNo_YDkFDJRDax2wHAKoSGn9csWcpHQEQW6WfsiuhdSOxwx27vxnCEt05U5UWcsEHxwcqZ6DZnXn0_IsnMSIfQlpPS058GW3KZZ7_TH8dQiZut5BEPIeUTpS4nQc-UbZ9HEveIU4UU7YpJB5mPgVHz9kTb8dELx7ua_b9w_tvt5-qu68fP9_e3FWu1TpXre4bL1W_Byt10_ZWWt-1KBVp54S1bQteCPAobE-o0O211q2TQja-UzQ01-z1Jbe8H0wqrckdXJxnctmIBkGqbl-oNxdqWePP0j-bKSRH42hniqdkBMhOQodaFFRcULfGlFbyZlnDZNezQTCbFXM0mxWzWTGgTLFSll495J_6iYZ_K381FODdBaDyF_eB1q1qEUBDWLemQwz_y_8Np_ee1Q</recordid><startdate>20180903</startdate><enddate>20180903</enddate><creator>Hou, Yongyong</creator><creator>Liu, Zhiyuan</creator><creator>Zuo, Zhuo</creator><creator>Gao, Tianchang</creator><creator>Fu, Jingqi</creator><creator>Wang, Huihui</creator><creator>Xu, Yuanyuan</creator><creator>Liu, Dianxin</creator><creator>Yamamoto, Masayuki</creator><creator>Zhu, Beibei</creator><creator>Zhang, Yiguo</creator><creator>Andersen, Melvin E.</creator><creator>Zhang, Qiang</creator><creator>Pi, Jingbo</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><scope>OTOTI</scope><orcidid>https://orcid.org/0000-0003-3871-428X</orcidid><orcidid>https://orcid.org/0000-0003-0227-8041</orcidid><orcidid>https://orcid.org/0000-0003-2354-9453</orcidid></search><sort><creationdate>20180903</creationdate><title>Adipocyte-specific deficiency of Nfe2l1 disrupts plasticity of white adipose tissues and metabolic homeostasis in mice</title><author>Hou, Yongyong ; Liu, Zhiyuan ; Zuo, Zhuo ; Gao, Tianchang ; Fu, Jingqi ; Wang, Huihui ; Xu, Yuanyuan ; Liu, Dianxin ; Yamamoto, Masayuki ; Zhu, Beibei ; Zhang, Yiguo ; Andersen, Melvin E. ; Zhang, Qiang ; Pi, Jingbo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c499t-49b3f56b70a5934ba5af84156e9cc2aa440f220f12abe161c79994c5253f86ed3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>60 APPLIED LIFE SCIENCES</topic><topic>Adipocytes - metabolism</topic><topic>Adipocytes - pathology</topic><topic>Adipose</topic><topic>ADIPOSE TISSUE</topic><topic>Adipose Tissue, White - cytology</topic><topic>Adipose Tissue, White - metabolism</topic><topic>Adipose Tissue, White - pathology</topic><topic>Adiposity</topic><topic>Animals</topic><topic>Body Fat Distribution</topic><topic>Energy Metabolism</topic><topic>Gene Expression Regulation</topic><topic>GLUCOSE</topic><topic>HOMEOSTASIS</topic><topic>Hypertrophy</topic><topic>INFLAMMATION</topic><topic>Inflammation - genetics</topic><topic>Inflammation - metabolism</topic><topic>Inflammation - pathology</topic><topic>INSULIN</topic><topic>Insulin Resistance</topic><topic>Lipolysis</topic><topic>Male</topic><topic>MICE</topic><topic>Mice, Knockout</topic><topic>NF-E2-Related Factor 1 - genetics</topic><topic>NFE2L1</topic><topic>Pyroptosis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hou, Yongyong</creatorcontrib><creatorcontrib>Liu, Zhiyuan</creatorcontrib><creatorcontrib>Zuo, Zhuo</creatorcontrib><creatorcontrib>Gao, Tianchang</creatorcontrib><creatorcontrib>Fu, Jingqi</creatorcontrib><creatorcontrib>Wang, Huihui</creatorcontrib><creatorcontrib>Xu, Yuanyuan</creatorcontrib><creatorcontrib>Liu, Dianxin</creatorcontrib><creatorcontrib>Yamamoto, Masayuki</creatorcontrib><creatorcontrib>Zhu, Beibei</creatorcontrib><creatorcontrib>Zhang, Yiguo</creatorcontrib><creatorcontrib>Andersen, Melvin E.</creatorcontrib><creatorcontrib>Zhang, Qiang</creatorcontrib><creatorcontrib>Pi, Jingbo</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><collection>OSTI.GOV</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hou, Yongyong</au><au>Liu, Zhiyuan</au><au>Zuo, Zhuo</au><au>Gao, Tianchang</au><au>Fu, Jingqi</au><au>Wang, Huihui</au><au>Xu, Yuanyuan</au><au>Liu, Dianxin</au><au>Yamamoto, Masayuki</au><au>Zhu, Beibei</au><au>Zhang, Yiguo</au><au>Andersen, Melvin E.</au><au>Zhang, Qiang</au><au>Pi, Jingbo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Adipocyte-specific deficiency of Nfe2l1 disrupts plasticity of white adipose tissues and metabolic homeostasis in mice</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2018-09-03</date><risdate>2018</risdate><volume>503</volume><issue>1</issue><spage>264</spage><epage>270</epage><pages>264-270</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>The maintenance of healthy adipose tissues is essential for efficient regulation of energy homeostasis. Nuclear factor-erythroid 2-related factor 1 (NFE2L1, also known as Nrf1), a CNC-bZIP protein, is a master regulator of the cellular adaptive response to stresses. To investigate the role of NFE2L1 in adipocytes, we bred a line of mice with adipocyte-specific Nfe2l1 knockout (Nfe2l1(f)-KO), and found that Nfe2l1(f)-KO mice exhibited a dramatically reduced subcutaneous adipose tissue (SAT) mass, insulin resistance, adipocyte hypertrophy, and severe adipose inflammation. Mechanistic studies revealed that Nfe2l1 deficiency may disturb the expression of lipolytic genes in adipocytes, leading to adipocyte hypertrophy followed by inflammation, pyroptosis, and insulin resistance. Our findings reveal a novel role for NFE2L1 in regulating adipose tissue plasticity and energy homeostasis.
•Nfe2l1(f)-KO mice exhibit diminished subcutaneous adipose tissues.•Nfe2l1(f)-KO mice show severe adipocyte hypertrophy and adipose inflammation.•Nfe2l1(f)-KO mice develop glucose intolerance and insulin resistance.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>29935181</pmid><doi>10.1016/j.bbrc.2018.06.013</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0003-3871-428X</orcidid><orcidid>https://orcid.org/0000-0003-0227-8041</orcidid><orcidid>https://orcid.org/0000-0003-2354-9453</orcidid></addata></record> |
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| subjects | 60 APPLIED LIFE SCIENCES Adipocytes - metabolism Adipocytes - pathology Adipose ADIPOSE TISSUE Adipose Tissue, White - cytology Adipose Tissue, White - metabolism Adipose Tissue, White - pathology Adiposity Animals Body Fat Distribution Energy Metabolism Gene Expression Regulation GLUCOSE HOMEOSTASIS Hypertrophy INFLAMMATION Inflammation - genetics Inflammation - metabolism Inflammation - pathology INSULIN Insulin Resistance Lipolysis Male MICE Mice, Knockout NF-E2-Related Factor 1 - genetics NFE2L1 Pyroptosis |
| title | Adipocyte-specific deficiency of Nfe2l1 disrupts plasticity of white adipose tissues and metabolic homeostasis in mice |
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