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Science 312 (5780): 1656-1659

Copyright © 2006 by the American Association for the Advancement of Science

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

Kenji Uno,1,2* Hideki Katagiri,2*{dagger} Tetsuya Yamada,1* Yasushi Ishigaki,1 Takehide Ogihara,2 Junta Imai,1,2 Yutaka Hasegawa,1,2 Junhong Gao,1,2 Keizo Kaneko,1,2 Hiroko Iwasaki,2 Hisamitsu Ishihara,1 Hironobu Sasano,3 Kouichi Inukai,4 Hiroyuki Mizuguchi,5 Tomoichiro Asano,6 Masakazu Shiota,7 Masamitsu Nakazato,8 Yoshitomo Oka1

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.

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.
6 Department of Physiological Chemistry and Metabolism, University of Tokyo, Tokyo 113–8655, Japan.
7 Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
8 Third Department of Internal Medicine, Miyazaki Medical College, University of Miyazaki, Kiyotake, Miyazaki 889–1692, Japan.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed E-mail: katagiri{at}

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