Prolactin improves hepatic steatosis via CD36 pathway
[Display omitted] •Circulating prolactin levels are negatively associated with the development of NAFLD.•Prolactin receptor expression is decreased in livers of obese patients in the presence of NAFLD.•Prolactin/prolactin receptor improved hepatic steatosis via suppression of hepatic CD36. Prolactin...
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| Veröffentlicht in: | Journal of hepatology 2018-06, Vol.68 (6), p.1247-1255 |
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| creator | Zhang, Pengzi Ge, Zhijuan Wang, Hongdong Feng, Wenhuan Sun, Xitai Chu, Xuehui Jiang, Can Wang, Yan Zhu, Dalong Bi, Yan |
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•Circulating prolactin levels are negatively associated with the development of NAFLD.•Prolactin receptor expression is decreased in livers of obese patients in the presence of NAFLD.•Prolactin/prolactin receptor improved hepatic steatosis via suppression of hepatic CD36.
Prolactin (PRL) is a multifunctional polypeptide with effects on metabolism, however, little is known about its effect on hepatic steatosis and lipid metabolism. Herein, we aimed to assess the role of PRL in the development of non-alcoholic fatty liver disease (NAFLD).
The serum PRL levels of 456 patients with NAFLD, 403 controls without NAFLD diagnosed by ultrasound, and 85 individuals with liver histology obtained during metabolic surgery (44 female and 30 male patients with NAFLD and 11 age-matched non-NAFLD female individuals) were evaluated. The expression of the gene encoding the prolactin receptor (PRLR) and signalling molecules involved in hepatic lipid metabolism were evaluated in human liver and HepG2 cells. The effects of overexpression of PRLR or fatty acid translocase (FAT)/CD36 or knockdown of PRLR on hepatic lipid metabolism were tested in free fatty acid (FFA)-treated HepG2 cells.
Circulating PRL levels were lower in individuals with ultrasound-diagnosed NAFLD (men: 7.9 [range, 5.9–10.3] µg/L; women: 8.7 [range, 6.1–12.4] µg/L) than those with non-NAFLD (men: 9.1 [range, 6.8–13.0] µg/L, p = 0.002; women: 11.6 [range, 8.2–16.1] µg/L, p |
| doi_str_mv | 10.1016/j.jhep.2018.01.035 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2003047591</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0168827818301156</els_id><sourcerecordid>2003047591</sourcerecordid><originalsourceid>FETCH-LOGICAL-c384t-96baaa24ec1ec32cab5d9f0ffe375010055520a4cc1f44686d1a07c8f78319223</originalsourceid><addsrcrecordid>eNp9kD1PwzAQhi0EglL4AwwoEgtLwvkrcSQWVD6lSjDAbLnORXWUNsVOi_rvcdTCwMB0wz3vq7uHkAsKGQWa3zRZM8dVxoCqDGgGXB6QEc0BUsgFPSSjCKlUsUKdkNMQGgDgUIpjcsJKIRmDckTkm-9aY3u3TNxi5bsNhiSWmt7ZJPRo-i64kGycSSb3PE_iYv5ltmfkqDZtwPP9HJOPx4f3yXM6fX16mdxNU8uV6NMynxljmEBL0XJmzUxWZQ11jbyQQAGklAyMsJbWQuQqr6iBwqq6UJyWjPExud71xss-1xh6vXDBYtuaJXbroNnwkShkSSN69QdturVfxusipbgCKoSMFNtR1ncheKz1yruF8VtNQQ9SdaMHqXqQqoHqKDWGLvfV69kCq9_Ij8UI3O4AjC42Dr0O1uHSYuU82l5Xnfuv_xtTboXc</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2083801445</pqid></control><display><type>article</type><title>Prolactin improves hepatic steatosis via CD36 pathway</title><source>Elsevier ScienceDirect Journals</source><creator>Zhang, Pengzi ; Ge, Zhijuan ; Wang, Hongdong ; Feng, Wenhuan ; Sun, Xitai ; Chu, Xuehui ; Jiang, Can ; Wang, Yan ; Zhu, Dalong ; Bi, Yan</creator><creatorcontrib>Zhang, Pengzi ; Ge, Zhijuan ; Wang, Hongdong ; Feng, Wenhuan ; Sun, Xitai ; Chu, Xuehui ; Jiang, Can ; Wang, Yan ; Zhu, Dalong ; Bi, Yan</creatorcontrib><description>[Display omitted]
•Circulating prolactin levels are negatively associated with the development of NAFLD.•Prolactin receptor expression is decreased in livers of obese patients in the presence of NAFLD.•Prolactin/prolactin receptor improved hepatic steatosis via suppression of hepatic CD36.
Prolactin (PRL) is a multifunctional polypeptide with effects on metabolism, however, little is known about its effect on hepatic steatosis and lipid metabolism. Herein, we aimed to assess the role of PRL in the development of non-alcoholic fatty liver disease (NAFLD).
The serum PRL levels of 456 patients with NAFLD, 403 controls without NAFLD diagnosed by ultrasound, and 85 individuals with liver histology obtained during metabolic surgery (44 female and 30 male patients with NAFLD and 11 age-matched non-NAFLD female individuals) were evaluated. The expression of the gene encoding the prolactin receptor (PRLR) and signalling molecules involved in hepatic lipid metabolism were evaluated in human liver and HepG2 cells. The effects of overexpression of PRLR or fatty acid translocase (FAT)/CD36 or knockdown of PRLR on hepatic lipid metabolism were tested in free fatty acid (FFA)-treated HepG2 cells.
Circulating PRL levels were lower in individuals with ultrasound-diagnosed NAFLD (men: 7.9 [range, 5.9–10.3] µg/L; women: 8.7 [range, 6.1–12.4] µg/L) than those with non-NAFLD (men: 9.1 [range, 6.8–13.0] µg/L, p = 0.002; women: 11.6 [range, 8.2–16.1] µg/L, p <0.001). PRL levels in patients with biopsy-proven severe hepatic steatosis were lower compared with those with mild-to-moderate hepatic steatosis in both men (8.3 [range, 5.4–9.5] µg/L vs. 9.7 [range, 7.1–12.3] µg/L, p = 0.031) and women (8.5 [range, 4.2–10.6] µg/L vs. 9.8 [range, 8.2–15.7] µg/L, p = 0.027). Furthermore, hepatic PRLR gene expression was significantly reduced in patients with NAFLD and negatively correlated with CD36 gene expression. In FFA-induced HepG2 cells, PRL treatment or PRLR overexpression significantly reduced the expression of CD36 and lipid content, effects that were abrogated after silencing of PRLR. Furthermore, overexpression of CD36 significantly reduced the PRL-mediated improvement in lipid content.
Our results reveal a novel association between the central nervous system and the liver, whereby PRL/PRLR improved hepatic lipid accumulation via the CD36 pathway.
Our clinical study suggests a negative association between prolactin (PRL)/prolactin receptor (PRLR) and the presence of non-alcoholic fatty liver disease (NAFLD). Using cell experiments, we found that PRL ameliorates hepatic steatosis via the hepatic PRLR and fatty acid translocase (FAT)/CD36, a key transporter of free fatty acid uptake in liver. Our findings suggest a novel approach to improving NAFLD using PRL and PRLR.
Clinical trial number: NCT03296605.</description><identifier>ISSN: 0168-8278</identifier><identifier>EISSN: 1600-0641</identifier><identifier>DOI: 10.1016/j.jhep.2018.01.035</identifier><identifier>PMID: 29452209</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Biopsy ; CD36 ; CD36 antigen ; Central nervous system ; Fatty liver ; Gene expression ; Hepatocytes ; Hepatology ; Lipid metabolism ; Lipids ; Liver diseases ; Non-alcoholic fatty liver disease ; Patients ; Polypeptides ; Prolactin ; Prolactin receptor ; Signal transduction ; STAT5 ; Steatosis ; Surgery ; Translocase ; Ultrasonic imaging ; Ultrasound</subject><ispartof>Journal of hepatology, 2018-06, Vol.68 (6), p.1247-1255</ispartof><rights>2018 European Association for the Study of the Liver</rights><rights>Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.</rights><rights>Copyright Elsevier Science Ltd. Jun 2018</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c384t-96baaa24ec1ec32cab5d9f0ffe375010055520a4cc1f44686d1a07c8f78319223</citedby><cites>FETCH-LOGICAL-c384t-96baaa24ec1ec32cab5d9f0ffe375010055520a4cc1f44686d1a07c8f78319223</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jhep.2018.01.035$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,45974</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29452209$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Pengzi</creatorcontrib><creatorcontrib>Ge, Zhijuan</creatorcontrib><creatorcontrib>Wang, Hongdong</creatorcontrib><creatorcontrib>Feng, Wenhuan</creatorcontrib><creatorcontrib>Sun, Xitai</creatorcontrib><creatorcontrib>Chu, Xuehui</creatorcontrib><creatorcontrib>Jiang, Can</creatorcontrib><creatorcontrib>Wang, Yan</creatorcontrib><creatorcontrib>Zhu, Dalong</creatorcontrib><creatorcontrib>Bi, Yan</creatorcontrib><title>Prolactin improves hepatic steatosis via CD36 pathway</title><title>Journal of hepatology</title><addtitle>J Hepatol</addtitle><description>[Display omitted]
•Circulating prolactin levels are negatively associated with the development of NAFLD.•Prolactin receptor expression is decreased in livers of obese patients in the presence of NAFLD.•Prolactin/prolactin receptor improved hepatic steatosis via suppression of hepatic CD36.
Prolactin (PRL) is a multifunctional polypeptide with effects on metabolism, however, little is known about its effect on hepatic steatosis and lipid metabolism. Herein, we aimed to assess the role of PRL in the development of non-alcoholic fatty liver disease (NAFLD).
The serum PRL levels of 456 patients with NAFLD, 403 controls without NAFLD diagnosed by ultrasound, and 85 individuals with liver histology obtained during metabolic surgery (44 female and 30 male patients with NAFLD and 11 age-matched non-NAFLD female individuals) were evaluated. The expression of the gene encoding the prolactin receptor (PRLR) and signalling molecules involved in hepatic lipid metabolism were evaluated in human liver and HepG2 cells. The effects of overexpression of PRLR or fatty acid translocase (FAT)/CD36 or knockdown of PRLR on hepatic lipid metabolism were tested in free fatty acid (FFA)-treated HepG2 cells.
Circulating PRL levels were lower in individuals with ultrasound-diagnosed NAFLD (men: 7.9 [range, 5.9–10.3] µg/L; women: 8.7 [range, 6.1–12.4] µg/L) than those with non-NAFLD (men: 9.1 [range, 6.8–13.0] µg/L, p = 0.002; women: 11.6 [range, 8.2–16.1] µg/L, p <0.001). PRL levels in patients with biopsy-proven severe hepatic steatosis were lower compared with those with mild-to-moderate hepatic steatosis in both men (8.3 [range, 5.4–9.5] µg/L vs. 9.7 [range, 7.1–12.3] µg/L, p = 0.031) and women (8.5 [range, 4.2–10.6] µg/L vs. 9.8 [range, 8.2–15.7] µg/L, p = 0.027). Furthermore, hepatic PRLR gene expression was significantly reduced in patients with NAFLD and negatively correlated with CD36 gene expression. In FFA-induced HepG2 cells, PRL treatment or PRLR overexpression significantly reduced the expression of CD36 and lipid content, effects that were abrogated after silencing of PRLR. Furthermore, overexpression of CD36 significantly reduced the PRL-mediated improvement in lipid content.
Our results reveal a novel association between the central nervous system and the liver, whereby PRL/PRLR improved hepatic lipid accumulation via the CD36 pathway.
Our clinical study suggests a negative association between prolactin (PRL)/prolactin receptor (PRLR) and the presence of non-alcoholic fatty liver disease (NAFLD). Using cell experiments, we found that PRL ameliorates hepatic steatosis via the hepatic PRLR and fatty acid translocase (FAT)/CD36, a key transporter of free fatty acid uptake in liver. Our findings suggest a novel approach to improving NAFLD using PRL and PRLR.
Clinical trial number: NCT03296605.</description><subject>Biopsy</subject><subject>CD36</subject><subject>CD36 antigen</subject><subject>Central nervous system</subject><subject>Fatty liver</subject><subject>Gene expression</subject><subject>Hepatocytes</subject><subject>Hepatology</subject><subject>Lipid metabolism</subject><subject>Lipids</subject><subject>Liver diseases</subject><subject>Non-alcoholic fatty liver disease</subject><subject>Patients</subject><subject>Polypeptides</subject><subject>Prolactin</subject><subject>Prolactin receptor</subject><subject>Signal transduction</subject><subject>STAT5</subject><subject>Steatosis</subject><subject>Surgery</subject><subject>Translocase</subject><subject>Ultrasonic imaging</subject><subject>Ultrasound</subject><issn>0168-8278</issn><issn>1600-0641</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNp9kD1PwzAQhi0EglL4AwwoEgtLwvkrcSQWVD6lSjDAbLnORXWUNsVOi_rvcdTCwMB0wz3vq7uHkAsKGQWa3zRZM8dVxoCqDGgGXB6QEc0BUsgFPSSjCKlUsUKdkNMQGgDgUIpjcsJKIRmDckTkm-9aY3u3TNxi5bsNhiSWmt7ZJPRo-i64kGycSSb3PE_iYv5ltmfkqDZtwPP9HJOPx4f3yXM6fX16mdxNU8uV6NMynxljmEBL0XJmzUxWZQ11jbyQQAGklAyMsJbWQuQqr6iBwqq6UJyWjPExud71xss-1xh6vXDBYtuaJXbroNnwkShkSSN69QdturVfxusipbgCKoSMFNtR1ncheKz1yruF8VtNQQ9SdaMHqXqQqoHqKDWGLvfV69kCq9_Ij8UI3O4AjC42Dr0O1uHSYuU82l5Xnfuv_xtTboXc</recordid><startdate>201806</startdate><enddate>201806</enddate><creator>Zhang, Pengzi</creator><creator>Ge, Zhijuan</creator><creator>Wang, Hongdong</creator><creator>Feng, Wenhuan</creator><creator>Sun, Xitai</creator><creator>Chu, Xuehui</creator><creator>Jiang, Can</creator><creator>Wang, Yan</creator><creator>Zhu, Dalong</creator><creator>Bi, Yan</creator><general>Elsevier B.V</general><general>Elsevier Science Ltd</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>201806</creationdate><title>Prolactin improves hepatic steatosis via CD36 pathway</title><author>Zhang, Pengzi ; Ge, Zhijuan ; Wang, Hongdong ; Feng, Wenhuan ; Sun, Xitai ; Chu, Xuehui ; Jiang, Can ; Wang, Yan ; Zhu, Dalong ; Bi, Yan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c384t-96baaa24ec1ec32cab5d9f0ffe375010055520a4cc1f44686d1a07c8f78319223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Biopsy</topic><topic>CD36</topic><topic>CD36 antigen</topic><topic>Central nervous system</topic><topic>Fatty liver</topic><topic>Gene expression</topic><topic>Hepatocytes</topic><topic>Hepatology</topic><topic>Lipid metabolism</topic><topic>Lipids</topic><topic>Liver diseases</topic><topic>Non-alcoholic fatty liver disease</topic><topic>Patients</topic><topic>Polypeptides</topic><topic>Prolactin</topic><topic>Prolactin receptor</topic><topic>Signal transduction</topic><topic>STAT5</topic><topic>Steatosis</topic><topic>Surgery</topic><topic>Translocase</topic><topic>Ultrasonic imaging</topic><topic>Ultrasound</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Pengzi</creatorcontrib><creatorcontrib>Ge, Zhijuan</creatorcontrib><creatorcontrib>Wang, Hongdong</creatorcontrib><creatorcontrib>Feng, Wenhuan</creatorcontrib><creatorcontrib>Sun, Xitai</creatorcontrib><creatorcontrib>Chu, Xuehui</creatorcontrib><creatorcontrib>Jiang, Can</creatorcontrib><creatorcontrib>Wang, Yan</creatorcontrib><creatorcontrib>Zhu, Dalong</creatorcontrib><creatorcontrib>Bi, Yan</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of hepatology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Pengzi</au><au>Ge, Zhijuan</au><au>Wang, Hongdong</au><au>Feng, Wenhuan</au><au>Sun, Xitai</au><au>Chu, Xuehui</au><au>Jiang, Can</au><au>Wang, Yan</au><au>Zhu, Dalong</au><au>Bi, Yan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prolactin improves hepatic steatosis via CD36 pathway</atitle><jtitle>Journal of hepatology</jtitle><addtitle>J Hepatol</addtitle><date>2018-06</date><risdate>2018</risdate><volume>68</volume><issue>6</issue><spage>1247</spage><epage>1255</epage><pages>1247-1255</pages><issn>0168-8278</issn><eissn>1600-0641</eissn><abstract>[Display omitted]
•Circulating prolactin levels are negatively associated with the development of NAFLD.•Prolactin receptor expression is decreased in livers of obese patients in the presence of NAFLD.•Prolactin/prolactin receptor improved hepatic steatosis via suppression of hepatic CD36.
Prolactin (PRL) is a multifunctional polypeptide with effects on metabolism, however, little is known about its effect on hepatic steatosis and lipid metabolism. Herein, we aimed to assess the role of PRL in the development of non-alcoholic fatty liver disease (NAFLD).
The serum PRL levels of 456 patients with NAFLD, 403 controls without NAFLD diagnosed by ultrasound, and 85 individuals with liver histology obtained during metabolic surgery (44 female and 30 male patients with NAFLD and 11 age-matched non-NAFLD female individuals) were evaluated. The expression of the gene encoding the prolactin receptor (PRLR) and signalling molecules involved in hepatic lipid metabolism were evaluated in human liver and HepG2 cells. The effects of overexpression of PRLR or fatty acid translocase (FAT)/CD36 or knockdown of PRLR on hepatic lipid metabolism were tested in free fatty acid (FFA)-treated HepG2 cells.
Circulating PRL levels were lower in individuals with ultrasound-diagnosed NAFLD (men: 7.9 [range, 5.9–10.3] µg/L; women: 8.7 [range, 6.1–12.4] µg/L) than those with non-NAFLD (men: 9.1 [range, 6.8–13.0] µg/L, p = 0.002; women: 11.6 [range, 8.2–16.1] µg/L, p <0.001). PRL levels in patients with biopsy-proven severe hepatic steatosis were lower compared with those with mild-to-moderate hepatic steatosis in both men (8.3 [range, 5.4–9.5] µg/L vs. 9.7 [range, 7.1–12.3] µg/L, p = 0.031) and women (8.5 [range, 4.2–10.6] µg/L vs. 9.8 [range, 8.2–15.7] µg/L, p = 0.027). Furthermore, hepatic PRLR gene expression was significantly reduced in patients with NAFLD and negatively correlated with CD36 gene expression. In FFA-induced HepG2 cells, PRL treatment or PRLR overexpression significantly reduced the expression of CD36 and lipid content, effects that were abrogated after silencing of PRLR. Furthermore, overexpression of CD36 significantly reduced the PRL-mediated improvement in lipid content.
Our results reveal a novel association between the central nervous system and the liver, whereby PRL/PRLR improved hepatic lipid accumulation via the CD36 pathway.
Our clinical study suggests a negative association between prolactin (PRL)/prolactin receptor (PRLR) and the presence of non-alcoholic fatty liver disease (NAFLD). Using cell experiments, we found that PRL ameliorates hepatic steatosis via the hepatic PRLR and fatty acid translocase (FAT)/CD36, a key transporter of free fatty acid uptake in liver. Our findings suggest a novel approach to improving NAFLD using PRL and PRLR.
Clinical trial number: NCT03296605.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>29452209</pmid><doi>10.1016/j.jhep.2018.01.035</doi><tpages>9</tpages></addata></record> |
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| subjects | Biopsy CD36 CD36 antigen Central nervous system Fatty liver Gene expression Hepatocytes Hepatology Lipid metabolism Lipids Liver diseases Non-alcoholic fatty liver disease Patients Polypeptides Prolactin Prolactin receptor Signal transduction STAT5 Steatosis Surgery Translocase Ultrasonic imaging Ultrasound |
| title | Prolactin improves hepatic steatosis via CD36 pathway |
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