{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T18:23:00Z","timestamp":1778782980472,"version":"3.51.4"},"reference-count":41,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T00:00:00Z","timestamp":1620086400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Lipotoxicity has been shown to cause dysfunction of many organs and tissues. However, it is unclear whether lipotoxicity is harmful to the somatotrophs, a kind of cell that synthesize growth hormone (GH) in the pituitary. In this study, we performed an epidemiological study, serum levels of triglyceride (TG) and GH showed a negative correlation, even after adjustment for potential confounders. In an animal study, male Sprague\u2010Dawley rats were fed a high\u2010fat diet (HFD) or a control diet for 28\u00a0weeks. HFD rats showed impaired GH synthesis, resulting in a decrease in circulating GH levels. The expression of pituitary Pit\u20101, a key transcription factor of GH, was inhibited. We found that the inositol\u2010requiring enzyme 1\u03b1 (IRE1\u03b1) pathway of endoplasmic reticulum (ER) stress was triggered in HFD rat pituitary glands and palmitic acid\u2010treated GH3 cells, respectively. On the contrary, applying 4\u2010phenyl butyric acid (4\u2010PBA) to alleviate ER stress or 4\u00b58c to specifically block the IRE1\u03b1 pathway attenuated the impairment of both Pit\u20101 and GH expression. In conclusion, we demonstrated that lipotoxicity directly inhibits the synthesis of GH, probably by reducing Pit\u20101 expression. The IRE1\u03b1 signaling pathway of ER stress may play an important role in this process.<\/jats:p>","DOI":"10.1111\/jcmm.16532","type":"journal-article","created":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T10:15:24Z","timestamp":1620123324000},"page":"5250-5259","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Lipotoxicity suppresses the synthesis of growth hormone in pituitary somatotrophs via endoplasmic reticulum stress"],"prefix":"10.1111","volume":"25","author":[{"given":"Ying","family":"Gong","sequence":"first","affiliation":[{"name":"Department of Endocrinology Shandong Provincial Hospital Cheeloo College of Medicine Shandong University Jinan China"},{"name":"Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism Jinan China"},{"name":"Shandong Institute of Endocrine and Metabolic Disease Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianmei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuoshuo","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Shandong Provincial Hospital Cheeloo College of Medicine Shandong University Jinan China"},{"name":"Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism Jinan China"},{"name":"Shandong Institute of Endocrine and Metabolic Disease Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Yang","sequence":"additional","affiliation":[{"name":"Experimental Animal Center Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1544-9746","authenticated-orcid":false,"given":"Ling","family":"Gao","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism Jinan China"},{"name":"Shandong Institute of Endocrine and Metabolic Disease Jinan China"},{"name":"Department of Endocrinology Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shanshan","family":"Shao","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism Jinan China"},{"name":"Shandong Institute of Endocrine and Metabolic Disease Jinan China"},{"name":"Department of Endocrinology Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3267-9292","authenticated-orcid":false,"given":"Jiajun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Shandong Provincial Hospital Cheeloo College of Medicine Shandong University Jinan China"},{"name":"Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism Jinan China"},{"name":"Shandong Institute of Endocrine and Metabolic Disease Jinan China"},{"name":"Department of Endocrinology Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,5,4]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2019.12.012"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-48382-5_8"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.1.7"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22423"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.6286"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.10045"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1817346"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.acthis.2016.03.005"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2017.10.009"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu11092228"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0739-7240(95)00059-3"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijo.0801289"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2012-1178"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41429-019-0219-3"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2020.01.019"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.00977"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.advms.2019.03.004"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-017-0183-y"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2019.116707"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00194.2018"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0954422410000168"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2016.06.008"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2017.03.014"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2016.05.002"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/5713249"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11695-017-2769-4"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-011-1211-9"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.032086"},{"key":"e_1_2_8_30_1","first-page":"2000","article-title":"Insulin restores UCP3 activity and decreases energy surfeit to alleviate lipotoxicity in skeletal muscle","volume":"40","author":"Tang W","year":"2017","journal-title":"Int J Mol Med"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12944-017-0561-z"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1159\/000125262"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-012513-104649"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2016.05.010"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0126384"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.REV119.007036"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.03.017"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.06.012"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1217611110"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e17-03-0144"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2011.05.002"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2014.02.008"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.16532","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jcmm.16532","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.16532","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T11:54:15Z","timestamp":1714391655000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.16532"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,4]]},"references-count":41,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["10.1111\/jcmm.16532"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.16532","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,4]]},"assertion":[{"value":"2020-11-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}