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

Autor: 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
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: iScience, Vol 23, Iss 3, Pp - (2020)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2020.100930
Popis: Summary: 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. : Obesity Medicine; Molecular Genetics Subject Areas: Obesity Medicine, Molecular Genetics
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