TY - JOUR
T1 - ChREBP-Mediated Regulation of Lipid Metabolism
T2 - Involvement of the Gut Microbiota, Liver, and Adipose Tissue
AU - Iizuka, Katsumi
AU - Takao, Ken
AU - Yabe, Daisuke
N1 - Funding Information:
This work was supported by grants from Japan Society for the Promotion of Sciences (JSPS) [KAKENHI Grant 17K00850 and 20K11645 (to K. I.) and 17K09825 (to D.Y.)].
Funding Information:
The authors thanks Professor Kosaku Uyeda (University of Texas) for their guidance and interest. The authors also thank the former and present members of the Department of Diabetes and Endocrinology, Gifu University Graduate School of Medicine, especially J. Takeda, Y. Horikawa, Y. Liu, W. Wu, and T. Kato, for helpful discussions. The authors also thank H. Tsuchida for technical assistance and M. Yato, Y. Ogiso, and M. Nozu for their secretarial assistance. Finally, we thank Mark Cleasby, PhD, from Edanz Group (https://en-author-services.edanzgroup.com/ac) for editing a draft of this manuscript.
Publisher Copyright:
© Copyright © 2020 Iizuka, Takao and Yabe.
PY - 2020/12/3
Y1 - 2020/12/3
N2 - Carbohydrate response element-binding protein (ChREBP) plays an important role in the development of type 2 diabetes, dyslipidemia, and non-alcoholic fatty liver disease, as well as tumorigenesis. ChREBP is highly expressed in lipogenic organs, such as liver, intestine, and adipose tissue, in which it regulates the production of acetyl CoA from glucose by inducing Pklr and Acyl expression. It has recently been demonstrated that ChREBP plays a role in the conversion of gut microbiota-derived acetate to acetyl CoA by activating its target gene, Acss2, in the liver. ChREBP regulates fatty acid synthesis, elongation, and desaturation by inducing Acc1 and Fasn, elongation of long-chain fatty acids family member 6 (encoded by Elovl6), and Scd1 expression, respectively. ChREBP also regulates the formation of very low-density lipoprotein by inducing the expression of Mtp. Furthermore, it plays a crucial role in peripheral lipid metabolism by inducing Fgf21 expression, as well as that of Angptl3 and Angptl8, which are known to reduce peripheral lipoprotein lipase activity. In addition, ChREBP is involved in the production of palmitic-acid-5-hydroxystearic-acid, which increases insulin sensitivity in adipose tissue. Curiously, ChREBP is indirectly involved in fatty acid β-oxidation and subsequent ketogenesis. Thus, ChREBP regulates whole-body lipid metabolism by controlling the transcription of lipogenic enzymes and liver-derived cytokines.
AB - Carbohydrate response element-binding protein (ChREBP) plays an important role in the development of type 2 diabetes, dyslipidemia, and non-alcoholic fatty liver disease, as well as tumorigenesis. ChREBP is highly expressed in lipogenic organs, such as liver, intestine, and adipose tissue, in which it regulates the production of acetyl CoA from glucose by inducing Pklr and Acyl expression. It has recently been demonstrated that ChREBP plays a role in the conversion of gut microbiota-derived acetate to acetyl CoA by activating its target gene, Acss2, in the liver. ChREBP regulates fatty acid synthesis, elongation, and desaturation by inducing Acc1 and Fasn, elongation of long-chain fatty acids family member 6 (encoded by Elovl6), and Scd1 expression, respectively. ChREBP also regulates the formation of very low-density lipoprotein by inducing the expression of Mtp. Furthermore, it plays a crucial role in peripheral lipid metabolism by inducing Fgf21 expression, as well as that of Angptl3 and Angptl8, which are known to reduce peripheral lipoprotein lipase activity. In addition, ChREBP is involved in the production of palmitic-acid-5-hydroxystearic-acid, which increases insulin sensitivity in adipose tissue. Curiously, ChREBP is indirectly involved in fatty acid β-oxidation and subsequent ketogenesis. Thus, ChREBP regulates whole-body lipid metabolism by controlling the transcription of lipogenic enzymes and liver-derived cytokines.
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U2 - 10.3389/fendo.2020.587189
DO - 10.3389/fendo.2020.587189
M3 - Review article
AN - SCOPUS:85097760759
SN - 1664-2392
VL - 11
JO - Frontiers in Endocrinology
JF - Frontiers in Endocrinology
M1 - 587189
ER -