Disease relevance of Mlxipl

• Carbohydrate response element-binding protein (ChREBP) is a rat homolog of human Williams-Beuren syndrome region 14 and a member of the basic helix-loop-helix leucine zipper transcription factor family [1].
• As a consequence, insulin signaling was improved in liver, skeletal muscles, and white adipose tissue, and overall glucose tolerance and insulin sensitivity were restored in ob/ob mice after a 7-day treatment with the recombinant adenovirus expressing shRNA against ChREBP [2].
• To investigate ChREBP's role in the development of obesity and obesity-associated metabolic dysregulation, ChREBP-deficient mice were intercrossed with ob/ob mice [3].

High impact information on Mlxipl

• The aim of our study was to assess the role of ChREBP in the control of L-PK and FAS gene expression by PUFAs [4].
• Polyunsaturated fatty acids suppress glycolytic and lipogenic genes through the inhibition of ChREBP nuclear protein translocation [4].
• Since glucose metabolism via the pentose phosphate pathway is determinant for ChREBP nuclear translocation, the decrease in xylulose 5-phosphate concentrations caused by a PUFA diet favors a PUFA-mediated inhibition of ChREBP translocation [4].
• Carbohydrate response element (ChRE)-binding protein (ChREBP) is a recently discovered transcription factor that is activated in response to high glucose concentrations in liver independently of insulin [5].
• Deficiency of carbohydrate response element-binding protein (ChREBP) reduces lipogenesis as well as glycolysis [6].

Biological context of Mlxipl

• Our studies also reveal that the loss of glucose effect observed in hGK-KO hepatocytes is associated with a decreased in the carbohydrate responsive element-binding protein (ChREBP) gene expression, a transcription factor suggested to mediate glucose signaling in liver [7].
• We show that T0901317 treatment of mice is associated with up-regulation of the ChREBP target gene, liver-type pyruvate kinase [8].
• In contrast, reporters containing non-glucose-responsive E box elements were not activated by ChREBP-Mlx expression [9].
• The ChREBP promoter contains functional LXR-binding sites that confer receptor-dependent binding and transactivation [8].
• When a plasmid expressing either Mlx or ChREBP was cotransfected with a ChoRE-containing reporter plasmid into human embryonic kidney 293 cells, no increase in promoter activity was observed [9].

Anatomical context of Mlxipl

• The detailed expression profile and transcriptional regulation of the ChREBP gene in adipocytes have not been characterized [1].
• ChREBP rather than USF2 regulates glucose stimulation of endogenous L-pyruvate kinase expression in insulin-secreting cells [10].

Associations of Mlxipl with chemical compounds

• ChREBP is able to bind to the carbohydrate response element on the promoter of L-type pyruvate kinase and initiate the gene transcription [1].
• The induction of ChREBP may serve as a novel pharmacological pathway for troglitazone-mediated hypoglycemic effects in vivo [1].
• Both endogenous and doxycycline-induced ChREBP proteins bind to the L-PK promoter in a glucose-dependent manner [10].

Other interactions of Mlxipl

• Together these results support a model whereby both SREBP-1c and glucose metabolism, acting via ChREBP, are necessary for the dietary induction of glycolytic and lipogenic gene expression in liver [7].
• We have recently demonstrated that carbohydrate responsive element-binding protein (ChREBP) plays a key role in the control of lipogenesis through the transcriptional regulation of lipogenic genes, including acetyl-CoA carboxylase and fatty acid synthase [2].
• Here, we demonstrated that (i) nuclear localization signal and basic helix-loop-helix/leucine-zipper domains of ChREBP were essential for the transcription, and (ii) these domains were the targets of regulation by cAMP and glucose [11].

References