Cideb, a member of CIDE family proteins, has emerged as an important regulator in the development of obesity and diabetes by controlling fatty acid synthesis and VLDL secretion in hepatocytes. Here, we investigated the role of Cideb in cholesterol biosynthesis, uptake and storage in the liver by using Cideb-null mice as a model system. Cideb-null mice and wild-type mice were treated with normal diet (ND) or high cholesterol diet (HCD) for one month. The metabolic parameters of cholesterol metabolism and expression profiles of genes in cholesterol biosynthesis and storage were measured. Cideb-null mice had lower levels of plasma cholesterol and LDL when fed with both ND and HCD and increased rate of cholesterol absorption. Furthermore, the liver of Cideb-null mice has lower rates of cholesterol biosynthesis and reduced expression levels of sterol response element-binding protein (SREBP) cleavage-activation protein (SCAP), and lower levels of nuclear form of SREBP2 and its downstream target genes in cholesterol biosynthesis pathway under a normal diet treatment. On the contrary, hepatic cholesterol biosynthesis rate between wild-type and Cideb-null mice was similar after high cholesterol diet treatment. Interestingly, hepatic cholesterol storage in the liver of Cideb-null mice was significantly increased due to its increased LDL receptor (LDLR) and acyl-CoA cholesterol acyltransferase (ACAT) expression. Finally, we observed drastically reduced cholesterol levels in the heart of Cideb-null mice fed with a high cholesterol diet. Overall, our data suggest that Cideb is a novel regulator in controlling cholesterol homeostasis in the liver. Therefore, Cideb could serve as an important therapeutical target for the treatment of atherosclerosis and cardiovascular diseases.

2007-01-01·Medical Hypotheses4区 · 医学

The CIDE genes might serve as novel targets for therapeutic intervention of obesity

4区 · 医学

Letter

作者: Daqing Zhao ; Guangsheng Chen ; Feng Zhang ; Qing Li ; Hang Li ; Yu Ma

Impaired activity of brown adipose tissue (BAT) is believed to have an important role in the development of obesity.It was found that CIDE-A, a member of the family of cell death-inducing DFF45 (DNA fragmentation factor 45)-like effectors, is highly expressed in BAT.Mice that are deficient for CIDE-A showed an increase in energy expenditure and are resistant to high-fat diet-induced obesity and diabetes.Therefore, CIDE-A offers a new option to explore the linkage between BAT and obesity.Recent evidence also suggests that CIDE-B might regulate the secretion of insulin and in this way it can accommodate the balance between energy intake and expenditure, which is important for the maintenance of body weight and normal physiol.Thus, it is suggested that the CIDE family might serve as novel targets for therapeutic intervention of obesity and type II diabetes.

2003-05-01·Journal of Biological Chemistry2区 · 生物学

The Hepatitis C Virus NS2 Protein Is an Inhibitor of CIDE-B-induced Apoptosis

2区 · 生物学

Article

作者: David Gilot ; Hervé Lerat ; Urszula Hibner ; Christiane Guguen-Guillouzo ; Nathalie Franck ; Lars Erdtmann ; Jacques Le Seyec ; Philippe Gripon ; Isabelle Cannie

Chronic hepatitis C virus (HCV) infection frequently leads to liver cancer. To determine the viral factor(s) potentially involved in viral persistence, we focused our work on NS2, a viral protein of unknown function. To assign a role for NS2, we searched for cellular proteins that interact with NS2. Performing a two-hybrid screen on a human liver cDNA library, we found that NS2 interacted with the liver-specific pro-apoptotic CIDE-B protein. Binding specificity of NS2 for CIDE-B was confirmed by cell-free assays associated with colocalization studies and coprecipitation experiments on human endogenous CIDE-B. CIDE-B, a member of the novel CIDE family of apoptosis-inducing factors, has been reported to show strong cell death-inducing activity in its C-terminal domain. We show that this CIDE-B killing domain is involved in the NS2 interaction. NS2 binding was sufficient to inhibit CIDE-B-induced apoptosis because an NS2 deletion mutant unable to interact with CIDE-B in vitro lost its capacity to interfere with CIDE-B cell death activity. Although it has been reported that CIDE-B-induced apoptosis is characterized by mitochondrial localization, the precise apoptotic mechanism remained unknown. Here, we show that CIDE-B induced cell death in a caspase-dependent manner through cytochrome c release from mitochondria. Furthermore, we found that NS2 counteracted the cytochrome c release induced by CIDE-B. In vivo, the CIDE-B protein level was extremely low in adenovirus-infected transgenic mice expressing the HCV polyprotein compared with that in wild-type mice. We suggest that NS2 interferes with the CIDE-B-induced death pathway and participates in HCV strategies to subvert host cell defense.

100 项与 CIDEB(Shanghai Argo Biopharma) 相关的药物交易

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