Brain leptin reduces liver lipids by increasing hepatic triglyceride secretion and lowering lipogenesis
| Autor: | Hackl, Martina Theresa, Fürnsinn, Clemens, Schuh, Christina Maria, Krssak, Martin, Carli, Fabrizia, Guerra, Sara, Freudenthaler, Angelika, Baumgartner-Parzer, Sabina, Helbich, Thomas H., Luger, Anton, Zeyda, Maximilian, Gastaldelli, Amalia, Buettner, Christoph, Scherer, Thomas |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Leptin
Male Lipoproteins Science Lipoproteins VLDL Diet High-Fat Article Polyethylene Glycols Rats Sprague-Dawley Stereotaxic Techniques Magnetic resonance imaging Animal disease models Non-alcoholic Fatty Liver Disease Animals Humans Fatty acids Sympathectomy lcsh:Science Triglycerides Injections Intraventricular Medulla Oblongata Lipogenesis digestive oral and skin physiology Vagus Nerve Rats Disease Models Animal Infusions Intraventricular Liver Blood-Brain Barrier ELISA lcsh:Q hormones hormone substitutes and hormone antagonists |
| Zdroj: | Nature Communications, Vol 10, Iss 1, Pp 1-13 (2019) Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-019-10684-1 |
| Popis: | 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. Obesity is associated with leptin resistance and rising blood leptin levels while central leptin exposure may be limited. Here, the authors show that brain leptin infusion reduces hepatic lipid content in rats by increasing hepatic VLDL secretion and lowering liver de novo lipogenesis via a vagal mechanism. |
| Databáze: | OpenAIRE |
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