Adiponectin Stimulates AMP-Activated Protein Kinase in the Hypothalamus and Increases Food Intake

Naoto Kubota; Wataru Yano; Tetsuya Kubota; Toshimasa Yamauchi; Shinsuke Itoh; Hiroki Kumagai; Hideki Kozono; Iseki Takamoto; Shiki Okamoto; Tetsuya Shiuchi; Ryo Suzuki; Hidemi Satoh; Atsushi Tsuchida; Masao Moroi; Kaoru Sugi; Tetsuo Noda; Hiroyuki Ebinuma; Yoichi Ueta; Tatsuya Kondo; Eiichi Araki; Osamu Ezaki; Ryozo Nagai; Kazuyuki Tobe; Yasuo Terauchi; Kohjiro Ueki; Yasuhiko Minokoshi; Takashi Kadowaki

doi:10.1016/j.cmet.2007.06.003

Adiponectin Stimulates AMP-Activated Protein Kinase in the Hypothalamus and Increases Food Intake

Naoto Kubota, Wataru Yano, Tetsuya Kubota, Toshimasa Yamauchi, Shinsuke Itoh, Hiroki Kumagai, Hideki Kozono, Iseki Takamoto, Shiki Okamoto, Tetsuya Shiuchi, Ryo Suzuki, Hidemi Satoh, Atsushi Tsuchida, Masao Moroi, Kaoru Sugi, Tetsuo Noda, Hiroyuki Ebinuma, Yoichi Ueta, Tatsuya Kondo, Eiichi ArakiOsamu Ezaki, Ryozo Nagai, Kazuyuki Tobe, Yasuo Terauchi, Kohjiro Ueki, Yasuhiko Minokoshi, Takashi Kadowaki^*

^*Corresponding author for this work

Faculty of Medicine

Research output: Contribution to journal › Article › peer-review

698 Scopus citations

Abstract

Adiponectin has been shown to stimulate fatty acid oxidation and enhance insulin sensitivity through the activation of AMP-activated protein kinase (AMPK) in the peripheral tissues. The effects of adiponectin in the central nervous system, however, are still poorly understood. Here, we show that adiponectin enhances AMPK activity in the arcuate hypothalamus (ARH) via its receptor AdipoR1 to stimulate food intake; this stimulation of food intake by adiponectin was attenuated by dominant-negative AMPK expression in the ARH. Moreover, adiponectin also decreased energy expenditure. Adiponectin-deficient mice showed decreased AMPK phosphorylation in the ARH, decreased food intake, and increased energy expenditure, exhibiting resistance to high-fat-diet-induced obesity. Serum and cerebrospinal fluid levels of adiponectin and expression of AdipoR1 in the ARH were increased during fasting and decreased after refeeding. We conclude that adiponectin stimulates food intake and decreases energy expenditure during fasting through its effects in the central nervous system.

Original language	English
Pages (from-to)	55-68
Number of pages	14
Journal	Cell Metabolism
Volume	6
Issue number	1
DOIs	https://doi.org/10.1016/j.cmet.2007.06.003
State	Published - 2007/07/11

Keywords

HUMDISEASE
MOLNEURO

ASJC Scopus subject areas

Physiology
Molecular Biology
Cell Biology

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10.1016/j.cmet.2007.06.003

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Kubota, N., Yano, W., Kubota, T., Yamauchi, T., Itoh, S., Kumagai, H., Kozono, H., Takamoto, I., Okamoto, S., Shiuchi, T., Suzuki, R., Satoh, H., Tsuchida, A., Moroi, M., Sugi, K., Noda, T., Ebinuma, H., Ueta, Y., Kondo, T., ... Kadowaki, T. (2007). Adiponectin Stimulates AMP-Activated Protein Kinase in the Hypothalamus and Increases Food Intake. Cell Metabolism, 6(1), 55-68. https://doi.org/10.1016/j.cmet.2007.06.003

@article{0ab86a1dc0204441a4c9e10893878a55,

title = "Adiponectin Stimulates AMP-Activated Protein Kinase in the Hypothalamus and Increases Food Intake",

abstract = "Adiponectin has been shown to stimulate fatty acid oxidation and enhance insulin sensitivity through the activation of AMP-activated protein kinase (AMPK) in the peripheral tissues. The effects of adiponectin in the central nervous system, however, are still poorly understood. Here, we show that adiponectin enhances AMPK activity in the arcuate hypothalamus (ARH) via its receptor AdipoR1 to stimulate food intake; this stimulation of food intake by adiponectin was attenuated by dominant-negative AMPK expression in the ARH. Moreover, adiponectin also decreased energy expenditure. Adiponectin-deficient mice showed decreased AMPK phosphorylation in the ARH, decreased food intake, and increased energy expenditure, exhibiting resistance to high-fat-diet-induced obesity. Serum and cerebrospinal fluid levels of adiponectin and expression of AdipoR1 in the ARH were increased during fasting and decreased after refeeding. We conclude that adiponectin stimulates food intake and decreases energy expenditure during fasting through its effects in the central nervous system.",

keywords = "HUMDISEASE, MOLNEURO",

author = "Naoto Kubota and Wataru Yano and Tetsuya Kubota and Toshimasa Yamauchi and Shinsuke Itoh and Hiroki Kumagai and Hideki Kozono and Iseki Takamoto and Shiki Okamoto and Tetsuya Shiuchi and Ryo Suzuki and Hidemi Satoh and Atsushi Tsuchida and Masao Moroi and Kaoru Sugi and Tetsuo Noda and Hiroyuki Ebinuma and Yoichi Ueta and Tatsuya Kondo and Eiichi Araki and Osamu Ezaki and Ryozo Nagai and Kazuyuki Tobe and Yasuo Terauchi and Kohjiro Ueki and Yasuhiko Minokoshi and Takashi Kadowaki",

note = "Funding Information: We thank H. Meguro, K. Takasawa, E. Yoshida-Nagata, N. Ohtsuka-Kowatari, A. Nagano, M. Nakashima, N. Kasuga, Y. Miki, and H. Chiyonobu for providing excellent technical assistance and animal care. This work was supported by a Grant-in-Aid for Creative Scientific Research from the Japan Society for the Promotion of Science (10NP0201), a grant from the Juvenile Diabetes Foundation International (1-2003-746), a Grant-in-Aid for the Development of Innovative Technology from the Ministry of Education, Culture, Sports, Science and Technology of Japan, Health Science Research grants (Research on Human Genome and Gene Therapy) from the Ministry of Health and Welfare, a grant for Promotion of Fundamental Studies in Health Science of the Organization for Pharmaceutical Safety and Research (to T. Kadowaki), a grant for Life & Socio-Medical Sciences from the Kanae Foundation, a grant from the Sankyo Foundation of Life Science, and a grant from Astellas Foundation for Research on Metabolic Disorders (to N.K.). ",

year = "2007",

month = jul,

day = "11",

doi = "10.1016/j.cmet.2007.06.003",

language = "英語",

volume = "6",

pages = "55--68",

journal = "Cell Metabolism",

issn = "1550-4131",

publisher = "Cell Press",

number = "1",

}

Kubota, N, Yano, W, Kubota, T, Yamauchi, T, Itoh, S, Kumagai, H, Kozono, H, Takamoto, I, Okamoto, S, Shiuchi, T, Suzuki, R, Satoh, H, Tsuchida, A, Moroi, M, Sugi, K, Noda, T, Ebinuma, H, Ueta, Y, Kondo, T, Araki, E, Ezaki, O, Nagai, R, Tobe, K, Terauchi, Y, Ueki, K, Minokoshi, Y & Kadowaki, T 2007, 'Adiponectin Stimulates AMP-Activated Protein Kinase in the Hypothalamus and Increases Food Intake', Cell Metabolism, vol. 6, no. 1, pp. 55-68. https://doi.org/10.1016/j.cmet.2007.06.003

TY - JOUR

T1 - Adiponectin Stimulates AMP-Activated Protein Kinase in the Hypothalamus and Increases Food Intake

AU - Kubota, Naoto

AU - Yano, Wataru

AU - Kubota, Tetsuya

AU - Yamauchi, Toshimasa

AU - Itoh, Shinsuke

AU - Kumagai, Hiroki

AU - Kozono, Hideki

AU - Takamoto, Iseki

AU - Okamoto, Shiki

AU - Shiuchi, Tetsuya

AU - Suzuki, Ryo

AU - Satoh, Hidemi

AU - Tsuchida, Atsushi

AU - Moroi, Masao

AU - Sugi, Kaoru

AU - Noda, Tetsuo

AU - Ebinuma, Hiroyuki

AU - Ueta, Yoichi

AU - Kondo, Tatsuya

AU - Araki, Eiichi

AU - Ezaki, Osamu

AU - Nagai, Ryozo

AU - Tobe, Kazuyuki

AU - Terauchi, Yasuo

AU - Ueki, Kohjiro

AU - Minokoshi, Yasuhiko

AU - Kadowaki, Takashi

N1 - Funding Information: We thank H. Meguro, K. Takasawa, E. Yoshida-Nagata, N. Ohtsuka-Kowatari, A. Nagano, M. Nakashima, N. Kasuga, Y. Miki, and H. Chiyonobu for providing excellent technical assistance and animal care. This work was supported by a Grant-in-Aid for Creative Scientific Research from the Japan Society for the Promotion of Science (10NP0201), a grant from the Juvenile Diabetes Foundation International (1-2003-746), a Grant-in-Aid for the Development of Innovative Technology from the Ministry of Education, Culture, Sports, Science and Technology of Japan, Health Science Research grants (Research on Human Genome and Gene Therapy) from the Ministry of Health and Welfare, a grant for Promotion of Fundamental Studies in Health Science of the Organization for Pharmaceutical Safety and Research (to T. Kadowaki), a grant for Life & Socio-Medical Sciences from the Kanae Foundation, a grant from the Sankyo Foundation of Life Science, and a grant from Astellas Foundation for Research on Metabolic Disorders (to N.K.).

PY - 2007/7/11

Y1 - 2007/7/11

N2 - Adiponectin has been shown to stimulate fatty acid oxidation and enhance insulin sensitivity through the activation of AMP-activated protein kinase (AMPK) in the peripheral tissues. The effects of adiponectin in the central nervous system, however, are still poorly understood. Here, we show that adiponectin enhances AMPK activity in the arcuate hypothalamus (ARH) via its receptor AdipoR1 to stimulate food intake; this stimulation of food intake by adiponectin was attenuated by dominant-negative AMPK expression in the ARH. Moreover, adiponectin also decreased energy expenditure. Adiponectin-deficient mice showed decreased AMPK phosphorylation in the ARH, decreased food intake, and increased energy expenditure, exhibiting resistance to high-fat-diet-induced obesity. Serum and cerebrospinal fluid levels of adiponectin and expression of AdipoR1 in the ARH were increased during fasting and decreased after refeeding. We conclude that adiponectin stimulates food intake and decreases energy expenditure during fasting through its effects in the central nervous system.

AB - Adiponectin has been shown to stimulate fatty acid oxidation and enhance insulin sensitivity through the activation of AMP-activated protein kinase (AMPK) in the peripheral tissues. The effects of adiponectin in the central nervous system, however, are still poorly understood. Here, we show that adiponectin enhances AMPK activity in the arcuate hypothalamus (ARH) via its receptor AdipoR1 to stimulate food intake; this stimulation of food intake by adiponectin was attenuated by dominant-negative AMPK expression in the ARH. Moreover, adiponectin also decreased energy expenditure. Adiponectin-deficient mice showed decreased AMPK phosphorylation in the ARH, decreased food intake, and increased energy expenditure, exhibiting resistance to high-fat-diet-induced obesity. Serum and cerebrospinal fluid levels of adiponectin and expression of AdipoR1 in the ARH were increased during fasting and decreased after refeeding. We conclude that adiponectin stimulates food intake and decreases energy expenditure during fasting through its effects in the central nervous system.

KW - HUMDISEASE

KW - MOLNEURO

UR - http://www.scopus.com/inward/record.url?scp=34347255023&partnerID=8YFLogxK

U2 - 10.1016/j.cmet.2007.06.003

DO - 10.1016/j.cmet.2007.06.003

M3 - 学術論文

C2 - 17618856

AN - SCOPUS:34347255023

SN - 1550-4131

VL - 6

SP - 55

EP - 68

JO - Cell Metabolism

JF - Cell Metabolism

IS - 1

ER -

Adiponectin Stimulates AMP-Activated Protein Kinase in the Hypothalamus and Increases Food Intake

Abstract

Keywords

ASJC Scopus subject areas

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