{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T01:51:39Z","timestamp":1760233899884,"version":"build-2065373602"},"reference-count":61,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,6]],"date-time":"2021-03-06T00:00:00Z","timestamp":1614988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","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\/501100010198","name":"Ministerio de Econom\u00eda, Industria y Competitividad, Gobierno de Espa\u00f1a","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\/501100010198","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Central actions of leptin and insulin on hepatic lipid metabolism can be opposing and the mechanism underlying this phenomenon remains unclear. Both hormones can modulate the central somatostatinergic system that has an inhibitory effect on growth hormone (GH) expression, which plays an important role in hepatic metabolism. Using a model of chronic central leptin infusion, we evaluated whether an increase in central leptin bioavailability modifies the serum lipid pattern through changes in hepatic lipid metabolism in male rats in response to an increase in central insulin and the possible involvement of the GH axis in these effects. We found a rise in serum GH in leptin plus insulin-treated rats, due to an increase in pituitary GH mRNA levels associated with lower hypothalamic somatostatin and pituitary somatostatin receptor-2 mRNA levels. An augment in hepatic lipolysis and a reduction in serum levels of non-esterified fatty acids (NEFA) and triglycerides were found in leptin-treated rats. These rats experienced a rise in lipogenic-related factors and normalization of serum levels of NEFA and triglycerides after insulin treatment. These results suggest that an increase in insulin in leptin-treated rats can act on the hepatic lipid metabolism through activation of the GH axis.<\/jats:p>","DOI":"10.3390\/cells10030581","type":"journal-article","created":{"date-parts":[[2021,3,7]],"date-time":"2021-03-07T20:20:43Z","timestamp":1615148443000},"page":"581","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cerebral Insulin Bolus Revokes the Changes in Hepatic Lipid Metabolism Induced by Chronic Central Leptin Infusion"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5507-7545","authenticated-orcid":false,"given":"Vicente","family":"Barrios","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, Instituto de Investigaci\u00f3n La Princesa, 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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"L\u00f3pez-Villar","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, Instituto de Investigaci\u00f3n La Princesa, E-28009 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5927-9240","authenticated-orcid":false,"given":"Laura M.","family":"Frago","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, Instituto de Investigaci\u00f3n La Princesa, 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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Canelles","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, Instituto de Investigaci\u00f3n La Princesa, 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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisca","family":"D\u00edaz-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Institute of Medical and Molecular Genetics (INGEMM), IdiPAZ, Hospital Universitario La Paz, Universidad Aut\u00f3noma de Madrid, E-28049 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6942-3023","authenticated-orcid":false,"given":"Emma","family":"Burgos-Ramos","sequence":"additional","affiliation":[{"name":"Faculty of Environmental Sciences and Biochemistry, Universidad de Castilla-La Mancha, E-45071 Toledo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8305-7154","authenticated-orcid":false,"given":"Gema","family":"Fr\u00fchbeck","sequence":"additional","affiliation":[{"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":"Metabolic Research Laboratory, Cl\u00ednica Universidad de Navarra, E-31008 Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4770-2291","authenticated-orcid":false,"given":"Julie A.","family":"Chowen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, Instituto de Investigaci\u00f3n La Princesa, 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":"IMDEA Food Institute, CEI UAM + CSIC, E-28049 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5826-0276","authenticated-orcid":false,"given":"Jes\u00fas","family":"Argente","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, Instituto de Investigaci\u00f3n La Princesa, 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":"IMDEA Food Institute, CEI UAM + CSIC, E-28049 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.molmet.2014.07.008","article-title":"Leptin receptor neurons in the dorsomedial hypothalamus are key regulators of energy expenditure and body weight, but not food intake","volume":"3","author":"Zadeh","year":"2014","journal-title":"Mol. 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