March 2023 - Matthäus Metz

English subtitles on Youtube available: click on the gear icon and select “Untertitel” – “English”

Dr. Matthäus Metz

MedUni Wien RESEARCHER OF THE MONTH March 2023

Metreleptin has been successfully used to treat the metabolic complications of lipodystrophy. In addition to its appetite suppressing effect, it also reduces liver fat content in these patients food intake independently. In rats, leptin signaling in the brain increases the release of lipids from the liver via the vagus nerve, thereby lowering liver fat content. In this randomized, placebo-controlled crossover study, we investigated whether a similar mechanism exists in humans. A single injection of metreleptin increased liver triglyceride export and decreased liver fat content in healthy men, but not in metabolically healthy liver transplant recipients who lack vagal innervation of the liver. Conversely, sensory stimulation of the vagus by modified sham feeding increased hepatic lipid release. Based on these observations we propose that metreleptin reduces hepatic lipid content by stimulating hepatic lipid release via a brain-vagus-liver axis in humans. 

Selected Literature

1. Metz M, Beghini M, Wolf P, et al. Leptin increases hepatic triglyceride export via a vagal mechanism in humans. Cell Metab 2022;34(11):1719-1731.e5. (In eng). DOI: 10.1016/j.cmet.2022.09.020.
2. Hackl MT, Fürnsinn C, Schuh CM, et al. Brain leptin reduces liver lipids by increasing hepatic triglyceride secretion and lowering lipogenesis. Nature communications 2019;10(1):2717. (In eng). DOI: 10.1038/s41467-019-10684-1.
3. Wolf P, Fellinger P, Pfleger L, et al. Gluconeogenesis, But Not Glycogenolysis, Contributes to the Increase in Endogenous Glucose Production by SGLT-2 Inhibition. Diabetes care 2021;44(2):541-548. (In eng). DOI: 10.2337/dc20-1983.
4. Beghini M, Wagner T, Luca AC, et al. Adipocyte STAT5 deficiency does not affect blood glucose homeostasis in obese mice. PLoS One 2021;16(11):e0260501. (In eng). DOI: 10.1371/journal.pone.0260501.
5. Kaplanian M, Philippe C, Eid SA, et al. Deciphering metformin action in obese mice: A critical re-evaluation of established protocols. Metabolism: clinical and experimental 2022;128:154956. (In eng). DOI: 10.1016/j.metabol.2021.154956.