{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T14:56:46Z","timestamp":1791212206803,"version":"4.1.0"},"reference-count":75,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,7,31]],"date-time":"2021-07-31T00:00:00Z","timestamp":1627689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001742","name":"United States-Israel Binational Science Foundation","doi-asserted-by":"publisher","award":["2013082"],"award-info":[{"award-number":["2013082"]}],"id":[{"id":"10.13039\/501100001742","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005674","name":"Cystinosis Research Foundation","doi-asserted-by":"publisher","award":["CRFS-2015-005"],"award-info":[{"award-number":["CRFS-2015-005"]}],"id":[{"id":"10.13039\/100005674","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Mice lacking the functional cystinosin gene (Ctns\u2212\/\u2212), a model of infantile nephropathic cystinosis (INC), exhibit the cachexia phenotype with adipose tissue browning and muscle wasting. Elevated leptin signaling is an important cause of chronic kidney disease-associated cachexia. The pegylated leptin receptor antagonist (PLA) binds to but does not activate the leptin receptor. We tested the efficacy of this PLA in Ctns\u2212\/\u2212 mice. We treated 12-month-old Ctns\u2212\/\u2212 mice and control mice with PLA (7 mg\/kg\/day, IP) or saline as a vehicle for 28 days. PLA normalized food intake and weight gain, increased fat and lean mass, decreased metabolic rate and improved muscle function. It also attenuated perturbations of energy homeostasis in adipose tissue and muscle in Ctns\u2212\/\u2212 mice. PLA attenuated adipose tissue browning in Ctns\u2212\/\u2212 mice. PLA increased gastrocnemius weight and fiber size as well as attenuated muscle fat infiltration in Ctns\u2212\/\u2212 mice. This was accompanied by correcting the increased expression of muscle wasting signaling while promoting the decreased expression of myogenesis in gastrocnemius of Ctns\u2212\/\u2212 mice. PLA attenuated aberrant expressed muscle genes that have been associated with muscle atrophy, increased energy expenditure and lipolysis in Ctns\u2212\/\u2212 mice. Leptin antagonism may represent a viable therapeutic strategy for adipose tissue browning and muscle wasting in INC.<\/jats:p>","DOI":"10.3390\/cells10081954","type":"journal-article","created":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T21:51:07Z","timestamp":1627854667000},"page":"1954","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["A Leptin Receptor Antagonist Attenuates Adipose Tissue Browning and Muscle Wasting in Infantile Nephropathic Cystinosis-Associated Cachexia"],"prefix":"10.3390","volume":"10","author":[{"given":"Alex","family":"Gonzalez","sequence":"first","affiliation":[{"name":"Division of Pediatric Nephrology, Rady Children\u2019s Hospital, University of California, San Diego, CA 92093-0831, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai W.","family":"Cheung","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nephrology, Rady Children\u2019s Hospital, University of California, San Diego, CA 92093-0831, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elliot A.","family":"Perens","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nephrology, Rady Children\u2019s Hospital, University of California, San Diego, CA 92093-0831, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo A.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nephrology, Rady Children\u2019s Hospital, University of California, San Diego, CA 92093-0831, USA"},{"name":"Health Sciences Postgraduate Program, School of Medicine, Federal University of Minas Gerais (UFMG), Belo Horizonte 30130-100, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arieh","family":"Gertler","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Food Science and Nutrition, Hebrew University of Jerusalem, Rehovot 7610001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert H.","family":"Mak","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nephrology, Rady Children\u2019s Hospital, University of California, San Diego, CA 92093-0831, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/ng0498-319","article-title":"A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis","volume":"18","author":"Town","year":"1998","journal-title":"Nat. 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