title: Insulin Regulates Hepatic Triglyceride Secretion and Lipid Content via Signaling in the Brain.
abstract: Hepatic steatosis is common in obesity and insulin resistance and results from a net retention of lipids in the liver. A key mechanism to prevent steatosis is to increase secretion of triglycerides (TG) packaged as VLDLs. Insulin controls nutrient partitioning via signaling through its cognate receptor in peripheral target organs such as liver, muscle, and adipose tissue and via signaling in the central nervous system (CNS) to orchestrate organ cross talk. While hepatic insulin signaling is known to suppress VLDL production from the liver, it is unknown whether brain insulin signaling independently regulates hepatic VLDL secretion. Here, we show that in conscious, unrestrained male Sprague Dawley rats the infusion of insulin into the third ventricle acutely increased hepatic TG secretion. Chronic infusion of insulin into the CNS via osmotic minipumps reduced the hepatic lipid content as assessed by noninvasive (1)H-MRS and lipid profiling independent of changes in hepatic de novo lipogenesis and food intake. In mice that lack the insulin receptor in the brain, hepatic TG secretion was reduced compared with wild-type littermate controls. These studies identify brain insulin as an important permissive factor in hepatic VLDL secretion that protects against hepatic steatosis.
authors: Departments of Medicine and Neuroscience, Diabetes, Obesity and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, NY Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria thomas.scherer@meduniwien.ac.at christoph.buettner@mssm.edu.
authors: Thomas
authors: T
authors: Scherer
authors: Departments of Medicine and Neuroscience, Diabetes, Obesity and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
authors: Claudia
authors: C
authors: Lindtner
authors: Departments of Medicine and Neuroscience, Diabetes, Obesity and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
authors: James
authors: J
authors: O'Hare
authors: Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
authors: Martina
authors: M
authors: Hackl
authors: Departments of Medicine and Neuroscience, Diabetes, Obesity and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
authors: Elizabeth
authors: E
authors: Zielinski
authors: Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
authors: Angelika
authors: A
authors: Freudenthaler
authors: Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
authors: Sabina
authors: S
authors: Baumgartner-Parzer
authors: Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Klaus
authors: K
authors: Tödter
authors: Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Joerg
authors: J
authors: Heeren
authors: Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria High Field MR Centre, Department of Biomedical Imaging and Image Guided Therapy, Medical University of Vienna, Vienna, Austria.
authors: Martin
authors: M
authors: Krššák
authors: Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Ludger
authors: L
authors: Scheja
authors: Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
authors: Clemens
authors: C
authors: Fürnsinn
authors: Departments of Medicine and Neuroscience, Diabetes, Obesity and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, NY thomas.scherer@meduniwien.ac.at christoph.buettner@mssm.edu.
authors: Christoph
authors: C
authors: Buettner
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D005234:Fatty Liver / Q000503:physiopathology; D007328:Insulin / Q000502:physiology*; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D007328:Insulin; D008079:Lipoproteins, VLDL; D014280:Triglycerides