{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T12:34:47Z","timestamp":1787747687486,"version":"build-2784847793"},"reference-count":50,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T00:00:00Z","timestamp":1615420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Spanish Ministry of Science and Innovation","doi-asserted-by":"publisher","award":["FIS PI19\/00166"],"award-info":[{"award-number":["FIS PI19\/00166"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["BFU 2017-82565-C2-1-R"],"award-info":[{"award-number":["BFU 2017-82565-C2-1-R"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Network Center for Biomedical Research on Obesity and Nutrition","award":["CIBER 06\/03"],"award-info":[{"award-number":["CIBER 06\/03"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The growth hormone (GH)\/insulin-like growth factor I (IGF-I) axis is involved in metabolic control. Malnutrition reduces IGF-I and modifies the thermogenic capacity of brown adipose tissue (BAT). Leptin has effects on the GH\/IGF-I axis and the function of BAT, but its interaction with IGF-I and the mechanisms involved in the regulation of thermogenesis remains unknown. We studied the GH\/IGF-I axis and activation of IGF-I-related signaling and metabolism related to BAT thermogenesis in chronic central leptin infused (L), pair-fed (PF), and control rats. Hypothalamic somatostatin mRNA levels were increased in PF and decreased in L, while pituitary GH mRNA was reduced in PF. Serum GH and IGF-I concentrations were decreased only in PF. In BAT, the association between suppressor of cytokine signaling 3 and the IGF-I receptor was reduced, and phosphorylation of the IGF-I receptor increased in the L group. Phosphorylation of Akt and cyclic AMP response element binding protein and glucose transporter 4 mRNA levels were increased in L and mRNA levels of uncoupling protein-1 (UCP-1) and enzymes involved in lipid anabolism reduced in PF. These results suggest that modifications in UCP-1 in BAT and changes in the GH\/IGF-I axis induced by negative energy balance are dependent upon leptin levels.<\/jats:p>","DOI":"10.3390\/ijms22062827","type":"journal-article","created":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T04:46:53Z","timestamp":1615438013000},"page":"2827","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Leptin Modulates the Response of Brown Adipose Tissue to Negative Energy Balance: Implication of the GH\/IGF-I Axis"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5507-7545","authenticated-orcid":false,"given":"Vicente","family":"Barrios","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Instituto de Investigaci\u00f3n La Princesa, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, E-28009 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBEROBN), Instituto de Salud Carlos III, E-28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5927-9240","authenticated-orcid":false,"given":"Laura M.","family":"Frago","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Instituto de Investigaci\u00f3n La Princesa, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, E-28009 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBEROBN), Instituto de Salud Carlos III, E-28029 Madrid, Spain"},{"name":"Department of Pediatrics, Faculty of Medicine, Universidad Aut\u00f3noma de Madrid, E-28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Canelles","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Instituto de Investigaci\u00f3n La Princesa, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, E-28009 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBEROBN), Instituto de Salud Carlos III, E-28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3999-8416","authenticated-orcid":false,"given":"Santiago","family":"Guerra-Cantera","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Instituto de Investigaci\u00f3n La Princesa, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, E-28009 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBEROBN), Instituto de Salud Carlos III, E-28029 Madrid, Spain"},{"name":"Department of Pediatrics, Faculty of Medicine, Universidad Aut\u00f3noma de Madrid, E-28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6744-6056","authenticated-orcid":false,"given":"Eduardo","family":"Arilla-Ferreiro","sequence":"additional","affiliation":[{"name":"Department of Biological Systems, Faculty of Medicine, Universidad de Alcal\u00e1, E-28871 Alcal\u00e1 de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4770-2291","authenticated-orcid":false,"given":"Julie A.","family":"Chowen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Instituto de Investigaci\u00f3n La Princesa, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, E-28009 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBEROBN), Instituto de Salud Carlos III, E-28029 Madrid, Spain"},{"name":"CEI UAM + CSIC, IMDEA Food Institute, E-28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5826-0276","authenticated-orcid":false,"given":"Jes\u00fas","family":"Argente","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Instituto de Investigaci\u00f3n La Princesa, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, E-28009 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBEROBN), Instituto de Salud Carlos III, E-28029 Madrid, Spain"},{"name":"Department of Pediatrics, Faculty of Medicine, Universidad Aut\u00f3noma de Madrid, E-28029 Madrid, Spain"},{"name":"CEI UAM + CSIC, IMDEA Food Institute, E-28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1016\/S1357-2725(98)00076-4","article-title":"Mammalian mitochondrial uncoupling proteins","volume":"30","author":"Jezek","year":"1998","journal-title":"Int. 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