Neuronal Pathway from the Liver Modulates Energy Expenditure and Systemic Insulin Sensitivity

Author:

Uno Kenji12345,Katagiri Hideki12345,Yamada Tetsuya12345,Ishigaki Yasushi12345,Ogihara Takehide12345,Imai Junta12345,Hasegawa Yutaka12345,Gao Junhong12345,Kaneko Keizo12345,Iwasaki Hiroko12345,Ishihara Hisamitsu12345,Sasano Hironobu12345,Inukai Kouichi12345,Mizuguchi Hiroyuki12345,Asano Tomoichiro12345,Shiota Masakazu12345,Nakazato Masamitsu12345,Oka Yoshitomo12345

Affiliation:

1. Division of Molecular Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai 980–8575, Japan.

2. Advanced Therapeutics for Metabolic Diseases, Center for Translational and Advanced Animal Research, Tohoku University Graduate School of Medicine, Sendai 980–8575, Japan.

3. Department of Pathology, Tohoku University Graduate School of Medicine, Sendai 980–8575, Japan.

4. The Fourth Department of Internal Medicine, Saitama Medical School, Moroyama, Iruma-gun, Saitama 350–0495, Japan.

5. Laboratory of Gene Transfer and Regulation, National Institute of Biomedical Innovation, Osaka 567–0085, Japan.

Abstract

Coordinated control of energy metabolism and glucose homeostasis requires communication between organs and tissues. We identified a neuronal pathway that participates in the cross talk between the liver and adipose tissue. By studying a mouse model, we showed that adenovirus-mediated expression of peroxisome proliferator–activated receptor (PPAR)–g2 in the liver induces acute hepatic steatosis while markedly decreasing peripheral adiposity. These changes were accompanied by increased energy expenditure and improved systemic insulin sensitivity. Hepatic vagotomy and selective afferent blockage of the hepatic vagus revealed that the effects on peripheral tissues involve the afferent vagal nerve. Furthermore, an antidiabetic thiazolidinedione, a PPARg agonist, enhanced this pathway. This neuronal pathway from the liver may function to protect against metabolic perturbation induced by excessive energy storage.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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