Hepatokine Pregnancy Zone Protein Governs the Diet‐Induced Thermogenesis Through Activating Brown Adipose Tissue
Intermittent fasting (IF), as a dietary intervention for weight loss, takes effects primarily through increasing energy expenditure. However, whether inter‐organ systems play a key role in IF remains unclear. Here, a novel hepatokine, pregnancy zone protein (PZP) is identified, which has significant...
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| Veröffentlicht in: | Advanced science 2021-11, Vol.8 (21), p.e2101991-n/a |
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| creator | Lin, Jun Jiang, Xiaoxiao Dong, Meng Liu, Xiaomeng Shen, Qiwei Huang, Yuanyuan Zhang, Hanlin Ye, Rongcai Zhou, Huiqiao Yan, Chunlong Yuan, Shouli Wu, Xiangnan Chen, Li Wang, Yanfang He, Min Tao, Yi Zhang, Zhaoyun Jin, Wanzhu |
| description | Intermittent fasting (IF), as a dietary intervention for weight loss, takes effects primarily through increasing energy expenditure. However, whether inter‐organ systems play a key role in IF remains unclear. Here, a novel hepatokine, pregnancy zone protein (PZP) is identified, which has significant induction during the refeeding stage of IF. Further, loss of function studies and protein therapeutic experiment in mice revealed that PZP promotes diet‐induced thermogenesis through activating brown adipose tissue (BAT). Mechanistically, circulating PZP can bind to cell surface glucose‐regulated protein of 78 kDa (GRP78) to promote uncoupling protein 1 (UCP1) expression via a p38 MAPK‐ATF2 signaling pathway in BAT. These studies illuminate a systemic regulation in which the IF promotes BAT thermogenesis through the endocrinal system and provide a novel potential target for treating obesity and related disorders.
This paper reports a novel hepatokine, pregnancy zone protein (PZP), which is significant induction by refeeding. Loss of function studies and protein therapeutic experiment in mice reveal that PZP promotes diet‐induced thermogenesis through activating brown adipose tissue (BAT) via p38 MAPK‐ATF2‐UCP1 signaling pathway in BAT. These studies provide a novel potential target for treating obesity and related disorders. |
| doi_str_mv | 10.1002/advs.202101991 |
| format | Article |
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This paper reports a novel hepatokine, pregnancy zone protein (PZP), which is significant induction by refeeding. Loss of function studies and protein therapeutic experiment in mice reveal that PZP promotes diet‐induced thermogenesis through activating brown adipose tissue (BAT) via p38 MAPK‐ATF2‐UCP1 signaling pathway in BAT. These studies provide a novel potential target for treating obesity and related disorders.</description><identifier>ISSN: 2198-3844</identifier><identifier>EISSN: 2198-3844</identifier><identifier>DOI: 10.1002/advs.202101991</identifier><identifier>PMID: 34514733</identifier><language>eng</language><publisher>Germany: John Wiley & Sons, Inc</publisher><subject>Adipose Tissue, Brown - metabolism ; Adult ; Animals ; Body fat ; Body mass index ; brown adipose tissue ; Cytochrome ; Diet, High-Fat ; Endoplasmic Reticulum Chaperone BiP - antagonists & inhibitors ; Endoplasmic Reticulum Chaperone BiP - genetics ; Endoplasmic Reticulum Chaperone BiP - metabolism ; Energy ; Female ; Food ; Gene expression ; Glucose Tolerance Test ; hepatokine ; Humans ; intermittent fasting ; Liver ; Male ; Metabolic disorders ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Middle Aged ; Obesity ; Obesity - metabolism ; Obesity - pathology ; Pregnancy Proteins - blood ; Pregnancy Proteins - genetics ; Pregnancy Proteins - metabolism ; Proteins ; RNA Interference ; RNA, Small Interfering - metabolism ; Signal Transduction ; Statistical analysis ; Thermogenesis ; Thermogenesis - physiology ; Uncoupling Protein 1 - deficiency ; Uncoupling Protein 1 - genetics ; Uncoupling Protein 1 - metabolism ; Weight control</subject><ispartof>Advanced science, 2021-11, Vol.8 (21), p.e2101991-n/a</ispartof><rights>2021 The Authors. Advanced Science published by Wiley‐VCH GmbH</rights><rights>2021 The Authors. Advanced Science published by Wiley-VCH GmbH.</rights><rights>2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5290-83f1aa302cef8cf9e90220dff487b8bd8636261729cce540a36dbc121f3e99a33</citedby><cites>FETCH-LOGICAL-c5290-83f1aa302cef8cf9e90220dff487b8bd8636261729cce540a36dbc121f3e99a33</cites><orcidid>0000-0002-5860-2958</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8564441/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8564441/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,1411,2096,11541,27901,27902,45550,45551,46027,46451,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34514733$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lin, Jun</creatorcontrib><creatorcontrib>Jiang, Xiaoxiao</creatorcontrib><creatorcontrib>Dong, Meng</creatorcontrib><creatorcontrib>Liu, Xiaomeng</creatorcontrib><creatorcontrib>Shen, Qiwei</creatorcontrib><creatorcontrib>Huang, Yuanyuan</creatorcontrib><creatorcontrib>Zhang, Hanlin</creatorcontrib><creatorcontrib>Ye, Rongcai</creatorcontrib><creatorcontrib>Zhou, Huiqiao</creatorcontrib><creatorcontrib>Yan, Chunlong</creatorcontrib><creatorcontrib>Yuan, Shouli</creatorcontrib><creatorcontrib>Wu, Xiangnan</creatorcontrib><creatorcontrib>Chen, Li</creatorcontrib><creatorcontrib>Wang, Yanfang</creatorcontrib><creatorcontrib>He, Min</creatorcontrib><creatorcontrib>Tao, Yi</creatorcontrib><creatorcontrib>Zhang, Zhaoyun</creatorcontrib><creatorcontrib>Jin, Wanzhu</creatorcontrib><title>Hepatokine Pregnancy Zone Protein Governs the Diet‐Induced Thermogenesis Through Activating Brown Adipose Tissue</title><title>Advanced science</title><addtitle>Adv Sci (Weinh)</addtitle><description>Intermittent fasting (IF), as a dietary intervention for weight loss, takes effects primarily through increasing energy expenditure. However, whether inter‐organ systems play a key role in IF remains unclear. Here, a novel hepatokine, pregnancy zone protein (PZP) is identified, which has significant induction during the refeeding stage of IF. Further, loss of function studies and protein therapeutic experiment in mice revealed that PZP promotes diet‐induced thermogenesis through activating brown adipose tissue (BAT). Mechanistically, circulating PZP can bind to cell surface glucose‐regulated protein of 78 kDa (GRP78) to promote uncoupling protein 1 (UCP1) expression via a p38 MAPK‐ATF2 signaling pathway in BAT. These studies illuminate a systemic regulation in which the IF promotes BAT thermogenesis through the endocrinal system and provide a novel potential target for treating obesity and related disorders.
This paper reports a novel hepatokine, pregnancy zone protein (PZP), which is significant induction by refeeding. Loss of function studies and protein therapeutic experiment in mice reveal that PZP promotes diet‐induced thermogenesis through activating brown adipose tissue (BAT) via p38 MAPK‐ATF2‐UCP1 signaling pathway in BAT. These studies provide a novel potential target for treating obesity and related disorders.</description><subject>Adipose Tissue, Brown - metabolism</subject><subject>Adult</subject><subject>Animals</subject><subject>Body fat</subject><subject>Body mass index</subject><subject>brown adipose tissue</subject><subject>Cytochrome</subject><subject>Diet, High-Fat</subject><subject>Endoplasmic Reticulum Chaperone BiP - antagonists & inhibitors</subject><subject>Endoplasmic Reticulum Chaperone BiP - genetics</subject><subject>Endoplasmic Reticulum Chaperone BiP - metabolism</subject><subject>Energy</subject><subject>Female</subject><subject>Food</subject><subject>Gene expression</subject><subject>Glucose Tolerance Test</subject><subject>hepatokine</subject><subject>Humans</subject><subject>intermittent fasting</subject><subject>Liver</subject><subject>Male</subject><subject>Metabolic disorders</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Middle Aged</subject><subject>Obesity</subject><subject>Obesity - metabolism</subject><subject>Obesity - pathology</subject><subject>Pregnancy Proteins - blood</subject><subject>Pregnancy Proteins - genetics</subject><subject>Pregnancy Proteins - metabolism</subject><subject>Proteins</subject><subject>RNA Interference</subject><subject>RNA, Small Interfering - metabolism</subject><subject>Signal Transduction</subject><subject>Statistical analysis</subject><subject>Thermogenesis</subject><subject>Thermogenesis - physiology</subject><subject>Uncoupling Protein 1 - deficiency</subject><subject>Uncoupling Protein 1 - genetics</subject><subject>Uncoupling Protein 1 - metabolism</subject><subject>Weight control</subject><issn>2198-3844</issn><issn>2198-3844</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><sourceid>DOA</sourceid><recordid>eNqFks1uEzEURi0EolXoliUaiQ2bBP_N2N4ghRbaSJVAIrBgYzn2nYnDxE7tmVTZ8Qg8I0_CpClRy4aVfe3j42vrQ-glwROCMX1r3DZPKKYEE6XIE3RKiZJjJjl_-mB-gs5yXmGMSckEJ_I5OmG8JFwwdorSFWxMF3_4AMXnBE0wwe6K7_GujB34UFzGLaSQi24JxYWH7vfPX7PgeguumC8hrWMDAbLPQ5Vi3yyLqe381nQ-NMX7FG9DMXV-EzMUc59zDy_Qs9q0Gc7uxxH6-vHD_PxqfP3pcnY-vR7bkio8lqwmxjBMLdTS1goUphS7uuZSLOTCyYpVtCKCKmuh5Niwyi0soaRmoJRhbIRmB6-LZqU3ya9N2ulovL5biKnRJnXetqAdFU7WlVDDPZwwtyiVE5KWChtRWyUH17uDa9Mv1uAshC6Z9pH08U7wS93ErZZlxfmgHKE394IUb3rInV77bKFtTYDYZ01LQSmhVbXv-_U_6Cr2KQxfNVCKYsyF3AsnB8qmmHOC-tgMwXqfDr1Phz6mYzjw6uETjvjfLAwAPwC3voXdf3R6evHtC1USsz_6CMfq</recordid><startdate>20211101</startdate><enddate>20211101</enddate><creator>Lin, Jun</creator><creator>Jiang, Xiaoxiao</creator><creator>Dong, Meng</creator><creator>Liu, Xiaomeng</creator><creator>Shen, Qiwei</creator><creator>Huang, Yuanyuan</creator><creator>Zhang, Hanlin</creator><creator>Ye, Rongcai</creator><creator>Zhou, Huiqiao</creator><creator>Yan, Chunlong</creator><creator>Yuan, Shouli</creator><creator>Wu, Xiangnan</creator><creator>Chen, Li</creator><creator>Wang, Yanfang</creator><creator>He, Min</creator><creator>Tao, Yi</creator><creator>Zhang, Zhaoyun</creator><creator>Jin, Wanzhu</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><general>Wiley</general><scope>24P</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>3V.</scope><scope>7XB</scope><scope>88I</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>M2O</scope><scope>M2P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-5860-2958</orcidid></search><sort><creationdate>20211101</creationdate><title>Hepatokine Pregnancy Zone Protein Governs the Diet‐Induced Thermogenesis Through Activating Brown Adipose Tissue</title><author>Lin, Jun ; Jiang, Xiaoxiao ; Dong, Meng ; Liu, Xiaomeng ; Shen, Qiwei ; Huang, Yuanyuan ; Zhang, Hanlin ; Ye, Rongcai ; Zhou, Huiqiao ; Yan, Chunlong ; Yuan, Shouli ; Wu, Xiangnan ; Chen, Li ; Wang, Yanfang ; He, Min ; Tao, Yi ; Zhang, Zhaoyun ; Jin, Wanzhu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5290-83f1aa302cef8cf9e90220dff487b8bd8636261729cce540a36dbc121f3e99a33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adipose Tissue, Brown - metabolism</topic><topic>Adult</topic><topic>Animals</topic><topic>Body fat</topic><topic>Body mass index</topic><topic>brown adipose tissue</topic><topic>Cytochrome</topic><topic>Diet, High-Fat</topic><topic>Endoplasmic Reticulum Chaperone BiP - antagonists & inhibitors</topic><topic>Endoplasmic Reticulum Chaperone BiP - genetics</topic><topic>Endoplasmic Reticulum Chaperone BiP - metabolism</topic><topic>Energy</topic><topic>Female</topic><topic>Food</topic><topic>Gene expression</topic><topic>Glucose Tolerance Test</topic><topic>hepatokine</topic><topic>Humans</topic><topic>intermittent fasting</topic><topic>Liver</topic><topic>Male</topic><topic>Metabolic disorders</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Middle Aged</topic><topic>Obesity</topic><topic>Obesity - metabolism</topic><topic>Obesity - pathology</topic><topic>Pregnancy Proteins - blood</topic><topic>Pregnancy Proteins - genetics</topic><topic>Pregnancy Proteins - metabolism</topic><topic>Proteins</topic><topic>RNA Interference</topic><topic>RNA, Small Interfering - metabolism</topic><topic>Signal Transduction</topic><topic>Statistical analysis</topic><topic>Thermogenesis</topic><topic>Thermogenesis - physiology</topic><topic>Uncoupling Protein 1 - deficiency</topic><topic>Uncoupling Protein 1 - genetics</topic><topic>Uncoupling Protein 1 - metabolism</topic><topic>Weight control</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lin, Jun</creatorcontrib><creatorcontrib>Jiang, Xiaoxiao</creatorcontrib><creatorcontrib>Dong, Meng</creatorcontrib><creatorcontrib>Liu, Xiaomeng</creatorcontrib><creatorcontrib>Shen, Qiwei</creatorcontrib><creatorcontrib>Huang, Yuanyuan</creatorcontrib><creatorcontrib>Zhang, Hanlin</creatorcontrib><creatorcontrib>Ye, Rongcai</creatorcontrib><creatorcontrib>Zhou, Huiqiao</creatorcontrib><creatorcontrib>Yan, Chunlong</creatorcontrib><creatorcontrib>Yuan, Shouli</creatorcontrib><creatorcontrib>Wu, Xiangnan</creatorcontrib><creatorcontrib>Chen, Li</creatorcontrib><creatorcontrib>Wang, Yanfang</creatorcontrib><creatorcontrib>He, Min</creatorcontrib><creatorcontrib>Tao, Yi</creatorcontrib><creatorcontrib>Zhang, Zhaoyun</creatorcontrib><creatorcontrib>Jin, Wanzhu</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>SciTech Premium Collection</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Advanced science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lin, Jun</au><au>Jiang, Xiaoxiao</au><au>Dong, Meng</au><au>Liu, Xiaomeng</au><au>Shen, Qiwei</au><au>Huang, Yuanyuan</au><au>Zhang, Hanlin</au><au>Ye, Rongcai</au><au>Zhou, Huiqiao</au><au>Yan, Chunlong</au><au>Yuan, Shouli</au><au>Wu, Xiangnan</au><au>Chen, Li</au><au>Wang, Yanfang</au><au>He, Min</au><au>Tao, Yi</au><au>Zhang, Zhaoyun</au><au>Jin, Wanzhu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hepatokine Pregnancy Zone Protein Governs the Diet‐Induced Thermogenesis Through Activating Brown Adipose Tissue</atitle><jtitle>Advanced science</jtitle><addtitle>Adv Sci (Weinh)</addtitle><date>2021-11-01</date><risdate>2021</risdate><volume>8</volume><issue>21</issue><spage>e2101991</spage><epage>n/a</epage><pages>e2101991-n/a</pages><issn>2198-3844</issn><eissn>2198-3844</eissn><abstract>Intermittent fasting (IF), as a dietary intervention for weight loss, takes effects primarily through increasing energy expenditure. However, whether inter‐organ systems play a key role in IF remains unclear. Here, a novel hepatokine, pregnancy zone protein (PZP) is identified, which has significant induction during the refeeding stage of IF. Further, loss of function studies and protein therapeutic experiment in mice revealed that PZP promotes diet‐induced thermogenesis through activating brown adipose tissue (BAT). Mechanistically, circulating PZP can bind to cell surface glucose‐regulated protein of 78 kDa (GRP78) to promote uncoupling protein 1 (UCP1) expression via a p38 MAPK‐ATF2 signaling pathway in BAT. These studies illuminate a systemic regulation in which the IF promotes BAT thermogenesis through the endocrinal system and provide a novel potential target for treating obesity and related disorders.
This paper reports a novel hepatokine, pregnancy zone protein (PZP), which is significant induction by refeeding. Loss of function studies and protein therapeutic experiment in mice reveal that PZP promotes diet‐induced thermogenesis through activating brown adipose tissue (BAT) via p38 MAPK‐ATF2‐UCP1 signaling pathway in BAT. These studies provide a novel potential target for treating obesity and related disorders.</abstract><cop>Germany</cop><pub>John Wiley & Sons, Inc</pub><pmid>34514733</pmid><doi>10.1002/advs.202101991</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0002-5860-2958</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adipose Tissue, Brown - metabolism Adult Animals Body fat Body mass index brown adipose tissue Cytochrome Diet, High-Fat Endoplasmic Reticulum Chaperone BiP - antagonists & inhibitors Endoplasmic Reticulum Chaperone BiP - genetics Endoplasmic Reticulum Chaperone BiP - metabolism Energy Female Food Gene expression Glucose Tolerance Test hepatokine Humans intermittent fasting Liver Male Metabolic disorders Mice Mice, Inbred C57BL Mice, Knockout Middle Aged Obesity Obesity - metabolism Obesity - pathology Pregnancy Proteins - blood Pregnancy Proteins - genetics Pregnancy Proteins - metabolism Proteins RNA Interference RNA, Small Interfering - metabolism Signal Transduction Statistical analysis Thermogenesis Thermogenesis - physiology Uncoupling Protein 1 - deficiency Uncoupling Protein 1 - genetics Uncoupling Protein 1 - metabolism Weight control |
| title | Hepatokine Pregnancy Zone Protein Governs the Diet‐Induced Thermogenesis Through Activating Brown Adipose Tissue |
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