Activation of AMPK-Regulated CRH Neurons in the PVH is Sufficient and Necessary to Induce Dietary Preference for Carbohydrate over Fat

Shiki Okamoto; Tatsuya Sato; Michihiro Tateyama; Haruaki Kageyama; Yuko Maejima; Masanori Nakata; Satoshi Hirako; Takashi Matsuo; Sanda Kyaw; Tetsuya Shiuchi; Chitoku Toda; Udval Sedbazar; Kumiko Saito; Nur Farehan Asgar; Boyang Zhang; Shigefumi Yokota; Kenta Kobayashi; Fabienne Foufelle; Pascal Ferré; Masamitsu Nakazato; Hiroaki Masuzaki; Seiji Shioda; Toshihiko Yada; Barbara B Kahn; Yasuhiko Minokoshi

doi:10.1016/j.celrep.2017.11.102

Activation of AMPK-Regulated CRH Neurons in the PVH is Sufficient and Necessary to Induce Dietary Preference for Carbohydrate over Fat

Cell Rep. 2018 Jan 16;22(3):706-721. doi: 10.1016/j.celrep.2017.11.102.

Authors

Shiki Okamoto¹, Tatsuya Sato², Michihiro Tateyama³, Haruaki Kageyama⁴, Yuko Maejima⁵, Masanori Nakata⁵, Satoshi Hirako⁶, Takashi Matsuo⁷, Sanda Kyaw⁸, Tetsuya Shiuchi⁹, Chitoku Toda⁹, Udval Sedbazar⁵, Kumiko Saito⁹, Nur Farehan Asgar², Boyang Zhang⁵, Shigefumi Yokota⁹, Kenta Kobayashi¹⁰, Fabienne Foufelle¹¹, Pascal Ferré¹¹, Masamitsu Nakazato¹², Hiroaki Masuzaki¹³, Seiji Shioda¹⁴, Toshihiko Yada⁵, Barbara B Kahn¹⁵, Yasuhiko Minokoshi¹⁶

Affiliations

¹ Division of Endocrinology and Metabolism, Department of Homeostatic Regulation, National Institute for Physiological Sciences, National Institute of Natural Sciences, 38 Nishigonaka, Myodaiji, Okazaki, Aichi 444-8585, Japan; Department of Physiological Sciences, School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), 38 Nishigonaka, Myodaiji, Okazaki, Aichi 444-8585, Japan; Second Department of Internal Medicine (Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology), Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Nakagami-gun, Okinawa 903-0215, Japan.
² Division of Endocrinology and Metabolism, Department of Homeostatic Regulation, National Institute for Physiological Sciences, National Institute of Natural Sciences, 38 Nishigonaka, Myodaiji, Okazaki, Aichi 444-8585, Japan; Department of Physiological Sciences, School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), 38 Nishigonaka, Myodaiji, Okazaki, Aichi 444-8585, Japan.
³ Department of Physiological Sciences, School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), 38 Nishigonaka, Myodaiji, Okazaki, Aichi 444-8585, Japan; Division of Biophysics and Neurobiology, Department of Molecular and Cellular Physiology, National Institute for Physiological Sciences, National Institute of Natural Sciences, 38 Nishigonaka, Myodaiji, Okazaki, Aichi 444-8585, Japan.
⁴ Department of Nutrition, Faculty of Health Care, Kiryu University, 606-7 Kasakake-cho Azami, Midori, Gunma 379-2392, Japan.
⁵ Division of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.
⁶ Department of Health and Nutrition, University of Human Arts and Sciences, 1288 Magome, Iwatsuki-ku, Saitama-shi, Saitama 339-8539, Japan.
⁷ Division of Endocrinology and Metabolism, Department of Homeostatic Regulation, National Institute for Physiological Sciences, National Institute of Natural Sciences, 38 Nishigonaka, Myodaiji, Okazaki, Aichi 444-8585, Japan; Division of Neurology, Respirology, Endocrinology, and Metabolism, Department of Internal Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
⁸ Division of Endocrinology and Metabolism, Department of Homeostatic Regulation, National Institute for Physiological Sciences, National Institute of Natural Sciences, 38 Nishigonaka, Myodaiji, Okazaki, Aichi 444-8585, Japan; Department of Physiology, University of Medicine 1, Yangon, Myanmar.
⁹ Division of Endocrinology and Metabolism, Department of Homeostatic Regulation, National Institute for Physiological Sciences, National Institute of Natural Sciences, 38 Nishigonaka, Myodaiji, Okazaki, Aichi 444-8585, Japan.
¹⁰ Department of Physiological Sciences, School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), 38 Nishigonaka, Myodaiji, Okazaki, Aichi 444-8585, Japan; Section of Viral Vector Development, National Institute for Physiological Sciences, National Institute of Natural Sciences, 38 Nishigonaka, Myodaiji, Okazaki, Aichi 444-8585, Japan.
¹¹ Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006 Paris, France; INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006 Paris, France.
¹² Division of Neurology, Respirology, Endocrinology, and Metabolism, Department of Internal Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
¹³ Second Department of Internal Medicine (Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology), Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Nakagami-gun, Okinawa 903-0215, Japan.
¹⁴ Division of Peptide Drug Innovation, Global Research Center for Innovative Life Science, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
¹⁵ Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
¹⁶ Division of Endocrinology and Metabolism, Department of Homeostatic Regulation, National Institute for Physiological Sciences, National Institute of Natural Sciences, 38 Nishigonaka, Myodaiji, Okazaki, Aichi 444-8585, Japan; Department of Physiological Sciences, School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), 38 Nishigonaka, Myodaiji, Okazaki, Aichi 444-8585, Japan. Electronic address: minokosh@nips.ac.jp.

PMID: 29346768
DOI: 10.1016/j.celrep.2017.11.102

Abstract

Food selection is essential for metabolic homeostasis and is influenced by nutritional state, food palatability, and social factors such as stress. However, the mechanism responsible for selection between a high-carbohydrate diet (HCD) and a high-fat diet (HFD) remains unknown. Here, we show that activation of a subset of corticotropin-releasing hormone (CRH)-positive neurons in the rostral region of the paraventricular hypothalamus (PVH) induces selection of an HCD over an HFD in mice during refeeding after fasting, resulting in a rapid recovery from the change in ketone metabolism. These neurons manifest activation of AMP-activated protein kinase (AMPK) during food deprivation, and this activation is necessary and sufficient for selection of an HCD over an HFD. Furthermore, this effect is mediated by carnitine palmitoyltransferase 1c (CPT1c). Thus, our results identify the specific neurons and intracellular signaling pathway responsible for regulation of the complex behavior of selection between an HCD and an HFD. VIDEO ABSTRACT.

Keywords: AMPK; CPT1c; CRH; PVH; food preference.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

AMP-Activated Protein Kinases / metabolism*
Animals
Carbohydrates
Corticotropin-Releasing Hormone / metabolism*
Diet
Male
Mice
Neurons / physiology*

Substances

Carbohydrates
Corticotropin-Releasing Hormone
AMP-Activated Protein Kinases

Grants and funding

R01 DK043051/DK/NIDDK NIH HHS/United States