CREBH Improves Diet-Induced Obesity, Insulin Resistance, and Metabolic Disturbances by FGF21-Dependent and FGF21-Independent Mechanisms

Aoi Satoh; Song iee Han; Masaya Araki; Yoshimi Nakagawa; Hiroshi Ohno; Yuhei Mizunoe; Kae Kumagai; Yuki Murayama; Yoshinori Osaki; Hitoshi Iwasaki; Motohiro Sekiya; Morichika Konishi; Nobuyuki Itoh; Takashi Matsuzaka; Hirohito Sone; Hitoshi Shimano

doi:10.1016/j.isci.2020.100930

CREBH Improves Diet-Induced Obesity, Insulin Resistance, and Metabolic Disturbances by FGF21-Dependent and FGF21-Independent Mechanisms

Aoi Satoh, Song iee Han, Masaya Araki, Yoshimi Nakagawa^*, Hiroshi Ohno, Yuhei Mizunoe, Kae Kumagai, Yuki Murayama, Yoshinori Osaki, Hitoshi Iwasaki, Motohiro Sekiya, Morichika Konishi, Nobuyuki Itoh, Takashi Matsuzaka, Hirohito Sone, Hitoshi Shimano

^*Corresponding author for this work

Complex Biosystem Research, Institute of Natural Medicine

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

12 Scopus citations

Abstract

Mice overexpressing the nuclear form of CREBH mainly in the liver (CREBH-Tg) showed suppression of high-fat high-sucrose (HFHS) diet-induced obesity accompanied by an increase in plasma fibroblast growth factor 21 (FGF21) levels. CREBH overexpression induced browning in inguinal white adipose tissue (WAT) and whole-body energy expenditure, which was canceled in Fgf21^−/− mice. Deficiency of FGF21 in CREBH-Tg mice mostly canceled the improvement of obesity, but the suppression of inflammation of epidermal WAT, amelioration of insulin resistance, and improvement of glucose metabolism still sustained. Kisspeptin 1 (Kiss1) was identified as a novel hormone target for CREBH to explain these FGF21-independent effects of CREBH. Knockdown of Kiss1 in HFHS-fed CREBH-Tg Fgf21^−/− mice showed partially canceled improvement of glucose metabolism. Taken together, we propose that hepatic CREBH pleiotropically improves diet-induced obesity-mediated dysfunctions in peripheral tissues by improving systemic energy metabolism in FGF21-dependent and FGF21-independent mechanisms.

Original language	English
Article number	100930
Journal	iScience
Volume	23
Issue number	3
DOIs	https://doi.org/10.1016/j.isci.2020.100930
State	Published - 2020/03/27

Keywords

Molecular Genetics
Obesity Medicine

ASJC Scopus subject areas

General

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.isci.2020.100930

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Satoh, A., Han, S. I., Araki, M., Nakagawa, Y., Ohno, H., Mizunoe, Y., Kumagai, K., Murayama, Y., Osaki, Y., Iwasaki, H., Sekiya, M., Konishi, M., Itoh, N., Matsuzaka, T., Sone, H., & Shimano, H. (2020). CREBH Improves Diet-Induced Obesity, Insulin Resistance, and Metabolic Disturbances by FGF21-Dependent and FGF21-Independent Mechanisms. iScience, 23(3), Article 100930. https://doi.org/10.1016/j.isci.2020.100930

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title = "CREBH Improves Diet-Induced Obesity, Insulin Resistance, and Metabolic Disturbances by FGF21-Dependent and FGF21-Independent Mechanisms",

abstract = "Mice overexpressing the nuclear form of CREBH mainly in the liver (CREBH-Tg) showed suppression of high-fat high-sucrose (HFHS) diet-induced obesity accompanied by an increase in plasma fibroblast growth factor 21 (FGF21) levels. CREBH overexpression induced browning in inguinal white adipose tissue (WAT) and whole-body energy expenditure, which was canceled in Fgf21−/− mice. Deficiency of FGF21 in CREBH-Tg mice mostly canceled the improvement of obesity, but the suppression of inflammation of epidermal WAT, amelioration of insulin resistance, and improvement of glucose metabolism still sustained. Kisspeptin 1 (Kiss1) was identified as a novel hormone target for CREBH to explain these FGF21-independent effects of CREBH. Knockdown of Kiss1 in HFHS-fed CREBH-Tg Fgf21−/− mice showed partially canceled improvement of glucose metabolism. Taken together, we propose that hepatic CREBH pleiotropically improves diet-induced obesity-mediated dysfunctions in peripheral tissues by improving systemic energy metabolism in FGF21-dependent and FGF21-independent mechanisms.",

keywords = "Molecular Genetics, Obesity Medicine",

author = "Aoi Satoh and Han, {Song iee} and Masaya Araki and Yoshimi Nakagawa and Hiroshi Ohno and Yuhei Mizunoe and Kae Kumagai and Yuki Murayama and Yoshinori Osaki and Hitoshi Iwasaki and Motohiro Sekiya and Morichika Konishi and Nobuyuki Itoh and Takashi Matsuzaka and Hirohito Sone and Hitoshi Shimano",

note = "Publisher Copyright: {\textcopyright} 2020 The Authors",

year = "2020",

month = mar,

day = "27",

doi = "10.1016/j.isci.2020.100930",

language = "英語",

volume = "23",

journal = "iScience",

issn = "2589-0042",

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number = "3",

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Satoh, A, Han, SI, Araki, M , Nakagawa, Y, Ohno, H, Mizunoe, Y, Kumagai, K, Murayama, Y, Osaki, Y, Iwasaki, H, Sekiya, M, Konishi, M, Itoh, N, Matsuzaka, T, Sone, H & Shimano, H 2020, 'CREBH Improves Diet-Induced Obesity, Insulin Resistance, and Metabolic Disturbances by FGF21-Dependent and FGF21-Independent Mechanisms', iScience, vol. 23, no. 3, 100930. https://doi.org/10.1016/j.isci.2020.100930

TY - JOUR

T1 - CREBH Improves Diet-Induced Obesity, Insulin Resistance, and Metabolic Disturbances by FGF21-Dependent and FGF21-Independent Mechanisms

AU - Satoh, Aoi

AU - Han, Song iee

AU - Araki, Masaya

AU - Nakagawa, Yoshimi

AU - Ohno, Hiroshi

AU - Mizunoe, Yuhei

AU - Kumagai, Kae

AU - Murayama, Yuki

AU - Osaki, Yoshinori

AU - Iwasaki, Hitoshi

AU - Sekiya, Motohiro

AU - Konishi, Morichika

AU - Itoh, Nobuyuki

AU - Matsuzaka, Takashi

AU - Sone, Hirohito

AU - Shimano, Hitoshi

PY - 2020/3/27

Y1 - 2020/3/27

N2 - Mice overexpressing the nuclear form of CREBH mainly in the liver (CREBH-Tg) showed suppression of high-fat high-sucrose (HFHS) diet-induced obesity accompanied by an increase in plasma fibroblast growth factor 21 (FGF21) levels. CREBH overexpression induced browning in inguinal white adipose tissue (WAT) and whole-body energy expenditure, which was canceled in Fgf21−/− mice. Deficiency of FGF21 in CREBH-Tg mice mostly canceled the improvement of obesity, but the suppression of inflammation of epidermal WAT, amelioration of insulin resistance, and improvement of glucose metabolism still sustained. Kisspeptin 1 (Kiss1) was identified as a novel hormone target for CREBH to explain these FGF21-independent effects of CREBH. Knockdown of Kiss1 in HFHS-fed CREBH-Tg Fgf21−/− mice showed partially canceled improvement of glucose metabolism. Taken together, we propose that hepatic CREBH pleiotropically improves diet-induced obesity-mediated dysfunctions in peripheral tissues by improving systemic energy metabolism in FGF21-dependent and FGF21-independent mechanisms.

AB - Mice overexpressing the nuclear form of CREBH mainly in the liver (CREBH-Tg) showed suppression of high-fat high-sucrose (HFHS) diet-induced obesity accompanied by an increase in plasma fibroblast growth factor 21 (FGF21) levels. CREBH overexpression induced browning in inguinal white adipose tissue (WAT) and whole-body energy expenditure, which was canceled in Fgf21−/− mice. Deficiency of FGF21 in CREBH-Tg mice mostly canceled the improvement of obesity, but the suppression of inflammation of epidermal WAT, amelioration of insulin resistance, and improvement of glucose metabolism still sustained. Kisspeptin 1 (Kiss1) was identified as a novel hormone target for CREBH to explain these FGF21-independent effects of CREBH. Knockdown of Kiss1 in HFHS-fed CREBH-Tg Fgf21−/− mice showed partially canceled improvement of glucose metabolism. Taken together, we propose that hepatic CREBH pleiotropically improves diet-induced obesity-mediated dysfunctions in peripheral tissues by improving systemic energy metabolism in FGF21-dependent and FGF21-independent mechanisms.

KW - Molecular Genetics

KW - Obesity Medicine

UR - http://www.scopus.com/inward/record.url?scp=85080993564&partnerID=8YFLogxK

U2 - 10.1016/j.isci.2020.100930

DO - 10.1016/j.isci.2020.100930

M3 - 学術論文

AN - SCOPUS:85080993564

SN - 2589-0042

VL - 23

JO - iScience

JF - iScience

IS - 3

M1 - 100930

ER -

CREBH Improves Diet-Induced Obesity, Insulin Resistance, and Metabolic Disturbances by FGF21-Dependent and FGF21-Independent Mechanisms

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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