Tags

Type your tag names separated by a space and hit enter

Brain leptin reduces liver lipids by increasing hepatic triglyceride secretion and lowering lipogenesis.
Nat Commun 2019; 10(1):2717NC

Abstract

Hepatic steatosis develops when lipid influx and production exceed the liver's ability to utilize/export triglycerides. Obesity promotes steatosis and is characterized by leptin resistance. A role of leptin in hepatic lipid handling is highlighted by the observation that recombinant leptin reverses steatosis of hypoleptinemic patients with lipodystrophy by an unknown mechanism. Since leptin mainly functions via CNS signaling, we here examine in rats whether leptin regulates hepatic lipid flux via the brain in a series of stereotaxic infusion experiments. We demonstrate that brain leptin protects from steatosis by promoting hepatic triglyceride export and decreasing de novo lipogenesis independently of caloric intake. Leptin's anti-steatotic effects are generated in the dorsal vagal complex, require hepatic vagal innervation, and are preserved in high-fat-diet-fed rats when the blood brain barrier is bypassed. Thus, CNS leptin protects from ectopic lipid accumulation via a brain-vagus-liver axis and may be a therapeutic strategy to ameliorate obesity-related steatosis.

Authors+Show Affiliations

Department of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria.Department of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria.Department of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria.Department of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria. Department of Biomedical Imaging and Image-Guided Therapy, High-Field MR Center, Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria. Christian Doppler Laboratory for Clinical Molecular MR Imaging, MOLIMA, Waehringer Guertel 18-20, 1090, Vienna, Austria.Institute of Clinical Physiology, National Research Council, Via G. Moruzzi 1, 56124, Pisa, Italy.Institute of Clinical Physiology, National Research Council, Via G. Moruzzi 1, 56124, Pisa, Italy. Institute of Life Sciences, Sant'Anna School of Advanced Studies, Via Santa Cecilia 3, 56127, Pisa, Italy.Department of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria.Department of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria.Department of Biomedical Imaging and Image-Guided Therapy, Division of Molecular and Gender Imaging, Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria.Department of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria.Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria.Institute of Clinical Physiology, National Research Council, Via G. Moruzzi 1, 56124, Pisa, Italy. Institute of Life Sciences, Sant'Anna School of Advanced Studies, Via Santa Cecilia 3, 56127, Pisa, Italy.Departments of Medicine and Neuroscience, and Diabetes, Obesity and Metabolism Institute (DOMI), Icahn School of Medicine at Mt Sinai, One Gustave L. Levy Pl, New York, NY, 10029, USA.Department of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria. thomas.scherer@meduniwien.ac.at.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31222048

Citation

Hackl, Martina Theresa, et al. "Brain Leptin Reduces Liver Lipids By Increasing Hepatic Triglyceride Secretion and Lowering Lipogenesis." Nature Communications, vol. 10, no. 1, 2019, p. 2717.
Hackl MT, Fürnsinn C, Schuh CM, et al. Brain leptin reduces liver lipids by increasing hepatic triglyceride secretion and lowering lipogenesis. Nat Commun. 2019;10(1):2717.
Hackl, M. T., Fürnsinn, C., Schuh, C. M., Krssak, M., Carli, F., Guerra, S., ... Scherer, T. (2019). Brain leptin reduces liver lipids by increasing hepatic triglyceride secretion and lowering lipogenesis. Nature Communications, 10(1), p. 2717. doi:10.1038/s41467-019-10684-1.
Hackl MT, et al. Brain Leptin Reduces Liver Lipids By Increasing Hepatic Triglyceride Secretion and Lowering Lipogenesis. Nat Commun. 2019 06 20;10(1):2717. PubMed PMID: 31222048.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Brain leptin reduces liver lipids by increasing hepatic triglyceride secretion and lowering lipogenesis. AU - Hackl,Martina Theresa, AU - Fürnsinn,Clemens, AU - Schuh,Christina Maria, AU - Krssak,Martin, AU - Carli,Fabrizia, AU - Guerra,Sara, AU - Freudenthaler,Angelika, AU - Baumgartner-Parzer,Sabina, AU - Helbich,Thomas H, AU - Luger,Anton, AU - Zeyda,Maximilian, AU - Gastaldelli,Amalia, AU - Buettner,Christoph, AU - Scherer,Thomas, Y1 - 2019/06/20/ PY - 2018/11/07/received PY - 2019/05/24/accepted PY - 2019/6/22/entrez PY - 2019/6/22/pubmed PY - 2019/7/10/medline SP - 2717 EP - 2717 JF - Nature communications JO - Nat Commun VL - 10 IS - 1 N2 - Hepatic steatosis develops when lipid influx and production exceed the liver's ability to utilize/export triglycerides. Obesity promotes steatosis and is characterized by leptin resistance. A role of leptin in hepatic lipid handling is highlighted by the observation that recombinant leptin reverses steatosis of hypoleptinemic patients with lipodystrophy by an unknown mechanism. Since leptin mainly functions via CNS signaling, we here examine in rats whether leptin regulates hepatic lipid flux via the brain in a series of stereotaxic infusion experiments. We demonstrate that brain leptin protects from steatosis by promoting hepatic triglyceride export and decreasing de novo lipogenesis independently of caloric intake. Leptin's anti-steatotic effects are generated in the dorsal vagal complex, require hepatic vagal innervation, and are preserved in high-fat-diet-fed rats when the blood brain barrier is bypassed. Thus, CNS leptin protects from ectopic lipid accumulation via a brain-vagus-liver axis and may be a therapeutic strategy to ameliorate obesity-related steatosis. SN - 2041-1723 UR - https://www.unboundmedicine.com/medline/citation/31222048/Brain_leptin_reduces_liver_lipids_by_increasing_hepatic_triglyceride_secretion_and_lowering_lipogenesis L2 - http://dx.doi.org/10.1038/s41467-019-10684-1 DB - PRIME DP - Unbound Medicine ER -