Leptin Increases Hepatic Triglyceride Export via a Vagal Mechanism in Humans
2022; RELX Group (Netherlands); Linguagem: Inglês
10.2139/ssrn.4078237
ISSN1556-5068
AutoresMatthäus Metz, Marianna Beghini, Peter Wolf, Lorenz Pfleger, Martina Häckl, Magdalena Bastian, Angelika Freudenthaler, Jürgen Harreiter, Maximilian Zeyda, Sabina Baumgartner‐Parzer, Rodrig Marculescu, Nara Marella, Thomas Hannich, Georg Györi, Gabriela Berlakovic, Michael Roden, Michael Krebs, Michael Trauner, Alexandra Kautzky-Willers, Martin Krššák, Herbert Stangl, Clemens Fürnsinn, Thomas Scherer,
Tópico(s)Adipose Tissue and Metabolism
ResumoRecombinant human leptin (metreleptin) reduces hepatic lipid content in patients with lipodystrophy and overweight non-alcoholic fatty liver disease patients with relative hypoleptinemia independent of its anorexic action. In rodents, CNS leptin signaling 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 we tested whether a comparable mechanism regulates hepatic lipid metabolism in humans. An acute metreleptin injection stimulated hepatic VLDL-TG secretion and reduced hepatic lipid content in fasted, lean men, but failed to do so in metabolically healthy liver transplant recipients, a model for hepatic denervation. In an independent cohort of lean men, 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.
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