scholarly journals Carbohydrate-Responsive Element-Binding Protein (ChREBP) Is a Negative Regulator of ARNT/HIF-1  Gene Expression in Pancreatic Islet  -Cells

Diabetes ◽  
2009 ◽  
Vol 59 (1) ◽  
pp. 153-160 ◽  
Author(s):  
N. A. Noordeen ◽  
T. K. Khera ◽  
G. Sun ◽  
E. R. Longbottom ◽  
T. J. Pullen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pancreatic Islet ◽  
Islet Cells ◽  
Binding Protein ◽  
Negative Regulator ◽  
Pancreatic Islet Cells ◽  
Element Binding Protein ◽  
Responsive Element

Abstract 540: Very Low Density Lipoprotein Assembly is Required for cAMP Responsive Element-binding Protein H Processing and Hepatic Apolipoprotein A-IV Expression in Mouse Models of Acute Steatosis

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Dongmei Cheng ◽  
Xu Xu ◽  
Elena Boudyguina ◽  
Trang Simon ◽  
Zhiyong Deng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mouse Models ◽  
Ketogenic Diet ◽  
Binding Protein ◽  
Apolipoprotein A ◽  
Vldl Secretion ◽  
Element Binding Protein ◽  
Vldl Assembly ◽  
Responsive Element ◽  
Camp Responsive Element Binding

Background: Our previous studies have demonstrated that hepatic expression of apolipoprotein A-IV (apoA-IV) is increased in mouse models of chronic steatosis and is closely correlated with hepatic triglyceride (TG) content. We have also shown that steatosis-induced hepatic apoA-IV gene expression is regulated by processing of the nuclear transcription factor cAMP responsive element-binding protein H (CREBH). Herein, we explored the mechanisms that mediate steatosis-induced CREBH processing. Methods: We measured hepatic CREBH processing, apoA-IV gene expression, and lipid content in several mouse models of attenuated or enhanced VLDL assembly that were subjected to acute steatosis induced by a 16 hour overnight fast or by feeding a ketogenic diet for 6 days. Results: Both fasting and the ketogenic diet induced acute hepatic TG accumulation associated with increased CREBH processing and apoA-IV gene expression, which were associated with hepatic TG content in C57BL/6 mice. All mouse models of attenuated VLDL secretion (shRNA-induced apoB knock down, liver specific microsomal triglyceride transfer protein (MTP) knockout, treatment with the MTP inhibitor BMS212122, and comparative gene identification-58 (CGI-58) deficiency) had increased hepatic TG accumulation, but displayed repressed CREBH processing and reduced apoA-IV gene expression compared to controls. When deficient VLDL assembly in liver-specific MTP knockout mice was reconstituted by adenoviral infection with a human MTP transgene, steatosis-induced CREBH processing and apoA-IV expression were restored. In a mouse model of enhanced VLDL assembly (transgenic overexpression of human MTP), apoA-IV gene expression correlated with bulk hepatic TG accumulation, but not with VLDL secretion rate, indicating that other steatosis-related factors participate in apoA-IV gene regulation. Conclusions: Taken together, these data provide compelling evidence that VLDL assembly and secretion is required for hepatic CREBH processing and enhanced apoA-IV gene expression in the setting of acute steatosis. These data further suggest that CREBH and apoA-IV play central roles in VLDL-mediated hepatic lipid efflux.

scholarly journals cAMP/Protein Kinase A Signaling Inhibits Dlx5 Expression via Activation of CREB and Subsequent C/EBPβ Induction in 3T3-L1 Preadipocytes

2018 ◽  
Vol 19 (10) ◽  
pp. 3161 ◽  
Author(s):  
Hye-Lim Lee ◽  
Abdul Qadir ◽  
Hyun-Jung Park ◽  
Eunkyung Chung ◽  
Yun-Sil Lee ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Binding Protein ◽  
Negative Regulator ◽  
Transcriptional Suppression ◽  
Enhancer Binding Protein ◽  
Element Binding Protein ◽  
Responsive Element ◽  
The Impact ◽  
Kinase A

Distal-less homeobox 5 (Dlx5) is a negative regulator of adipogenesis. Dlx5 expression is decreased by adipogenic stimuli, but the mechanisms of Dlx5 downregulation by adipogenic stimuli have not yet been determined. Here, we tested the impact of cAMP/PKA (protein kinase A) signaling induced by 3-isobutyl-1 methyl xanthine (IBMX), forskolin, and 8-CPT-cAMP on the expression of Dlx5 in 3T3-L1 preadipocytes. Significant downregulation of Dlx5 mRNA expression and protein production levels were observed via cAMP/PKA-dependent signaling. Forced expression of cAMP-responsive element-binding protein (CREB) and CCAAT/enhancer-binding protein β (C/EBPβ) was sufficient for downregulation of Dlx5 expression and revealed that CREB functions upstream of C/EBPβ. In addition, C/EBPβ knockdown by siRNA rescued Dlx5 expression in IBMX-treated 3T3-L1 preadipocytes. Luciferase assays using a Dlx5-luc-2935 reporter construct demonstrated the requirement of the Dlx5 promoter region, ranging from −774 to −95 bp that contains two putative C/EBPβ binding elements (site-1: −517 to −510 bp and site-2: −164 to −157 bp), in the suppression of Dlx5 transcription. Consequently, chromatin immunoprecipitation analysis confirmed the importance of site-1, but not site-2, in C/EBPβ binding and transcriptional suppression of Dlx5. In conclusion, we elucidated the underling mechanism of Dlx5 downregulation in IBMX-induced adipogenesis. IBMX activated cAMP/PKA/CREB signaling and subsequently upregulated C/EBPβ, which binds to the Dlx5 promoter to suppress Dlx5 transcription.

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