{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T03:29:46Z","timestamp":1784258986481,"version":"3.55.0"},"reference-count":104,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2020,11,19]],"date-time":"2020-11-19T00:00:00Z","timestamp":1605744000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,11,19]],"date-time":"2020-11-19T00:00:00Z","timestamp":1605744000000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,11,19]],"date-time":"2020-11-19T00:00:00Z","timestamp":1605744000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["617\/14"],"award-info":[{"award-number":["617\/14"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["158\/18"],"award-info":[{"award-number":["158\/18"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007293","name":"Obesity Society","doi-asserted-by":"publisher","award":["Early Career Research Award"],"award-info":[{"award-number":["Early Career Research Award"]}],"id":[{"id":"10.13039\/100007293","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ERC-2015-StG grant","award":["676841"],"award-info":[{"award-number":["676841"]}]},{"name":"Hungarian National Research, Development, and Innovation Office","award":["NKFI-6\/FK_124038"],"award-info":[{"award-number":["NKFI-6\/FK_124038"]}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    The soluble isoform of leptin receptor (sOb-R), secreted by the liver, regulates leptin bioavailability and bioactivity. Its reduced levels in diet-induced obesity (DIO) contribute to hyperleptinemia and leptin resistance, effects that are regulated by the endocannabinoid (eCB)\/CB\n                    <jats:sub>1<\/jats:sub>\n                    R system. Here we show that pharmacological activation\/blockade and genetic overexpression\/deletion of hepatic CB\n                    <jats:sub>1<\/jats:sub>\n                    R modulates sOb-R levels and hepatic leptin resistance. Interestingly, peripheral CB\n                    <jats:sub>1<\/jats:sub>\n                    R blockade failed to reverse DIO-induced reduction of sOb-R levels, increased fat mass and dyslipidemia, and hepatic steatosis in mice lacking C\/EBP homologous protein (CHOP), whereas direct activation of CB\n                    <jats:sub>1<\/jats:sub>\n                    R in wild-type hepatocytes reduced sOb-R levels in a CHOP-dependent manner. Moreover, CHOP stimulation increased sOb-R expression and release via a direct regulation of its promoter, while CHOP deletion reduced leptin sensitivity. Our findings highlight a novel molecular aspect by which the hepatic eCB\/CB\n                    <jats:sub>1<\/jats:sub>\n                    R system is involved in the development of hepatic leptin resistance and in the regulation of sOb-R levels via CHOP.\n                  <\/jats:p>","DOI":"10.7554\/elife.60771","type":"journal-article","created":{"date-parts":[[2020,11,19]],"date-time":"2020-11-19T08:02:37Z","timestamp":1605772957000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.60771","source":"Crossref","is-referenced-by-count":26,"title":["CB1R regulates soluble leptin receptor levels via CHOP, contributing to hepatic leptin resistance"],"prefix":"10.7554","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5790-9544","authenticated-orcid":true,"given":"Adi","family":"Drori","sequence":"first","affiliation":[{"name":"Obesity and Metabolism Laboratory, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, 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Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerg\u0151","family":"Szanda","sequence":"additional","affiliation":[{"name":"MTA-SE Laboratory of Molecular Physiology, Department of Physiology, Semmelweis University, Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maayan","family":"Salton","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, The Institute for Medical Research Israel-Canada, The Hebrew University of Jerusalem, Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8067-6577","authenticated-orcid":true,"given":"Boaz","family":"Tirosh","sequence":"additional","affiliation":[{"name":"The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, 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