Brain Leptin Reduces Liver Lipids by Increasing Hepatic Triglyceride Secretion and Lowering Lipogenesis

Overview

Journal Nat Commun

Specialty Biology

Date 2019 Jun 22

PMID 31222048

Citations 39

Authors

Martina Theresa Hackl

Clemens Furnsinn

Christina Maria Schuh

Martin Krssak

Fabrizia Carli

Sara Guerra

Angelika Freudenthaler

Sabina Baumgartner-Parzer

Thomas H Helbich

Anton Luger

Maximilian Zeyda

Amalia Gastaldelli

Christoph Buettner

Thomas Scherer

Affiliations

Soon will be listed here.

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.

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