| Autor: |
Matthäus Metz, Marianna Beghini, Peter Wolf, Lorenz Pfleger, Martina Hackl, Magdalena Bastian, Angelika Freudenthaler, Jürgen Harreiter, Maximilian Zeyda, Sabina Baumgartner-Parzer, Rodrig Marculescu, Nara Marella, J. Thomas Hannich, Georg Györi, Gabriela Berlakovich, Michael Roden, Michael Krebs, Robert Risti, Aivar Lõokene, Michael Trauner, Alexandra Kautzky-Willer, Martin Krššák, Herbert Stangl, Clemens Fürnsinn, Thomas Scherer |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Cell Metabolism. 34:1719-1731.e5 |
| ISSN: |
1550-4131 |
| DOI: |
10.1016/j.cmet.2022.09.020 |
| Popis: |
Recombinant human leptin (metreleptin) reduces hepatic lipid content in patients with lipodystrophy and overweight patients with non-alcoholic fatty liver disease and relative hypoleptinemia independent of its anorexic action. In rodents, leptin signaling in the brain increases very-low-density lipoprotein triglyceride (VLDL-TG) secretion and reduces hepatic lipid content via the vagus nerve. In this randomized, placebo-controlled crossover trial (EudraCT Nr. 2017-003014-22), we tested whether a comparable mechanism regulates hepatic lipid metabolism in humans. A single metreleptin injection stimulated hepatic VLDL-TG secretion (primary outcome) and reduced hepatic lipid content in fasted, lean men (n = 13, age range 20-38 years) but failed to do so in metabolically healthy liver transplant recipients (n = 9, age range 26-62 years) who represent a model for hepatic denervation. In an independent cohort of lean men (n = 10, age range 23-31 years), vagal stimulation by modified sham feeding replicated the effects of metreleptin on VLDL-TG secretion. Therefore, we propose that leptin has anti-steatotic properties that are independent of food intake by stimulating hepatic VLDL-TG export via a brain-vagus-liver axis. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
