Author:
Iizuka Katsumi,Takao Ken,Yabe Daisuke
Abstract
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 inducingPklrandAcylexpression. 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 inducingAcc1andFasn, elongation of long-chain fatty acids family member 6 (encoded byElovl6), andScd1expression, respectively. ChREBP also regulates the formation of very low-density lipoprotein by inducing the expression ofMtp. Furthermore, it plays a crucial role in peripheral lipid metabolism by inducing Fgf21expression, as well as that ofAngptl3andAngptl8, 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.
Funder
Japan Society for the Promotion of Science
Subject
Endocrinology, Diabetes and Metabolism
Cited by
84 articles.
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