Authors: ZHAO, YULAN; CHAN, MEI-YEN; ZHOU, SHULI; HENG, CHEW-KIAT

Source: Gene Expression, Volume 14, Number 3, 2007 , pp. 149-158(10)

Publisher: Cognizant Communication Corporation

Abstract:

This study investigated the early and long-term effects of atherogenic diet on hepatic gene expression, and the restorative effects of atorvastatin in treating hypercholesterolemia. Two groups of female C57BL/6J mice were fed standard chow or atherogenic diet for 1-week early phase study and two other groups for 10 weeks. The fifth group had daily 10 mg/kg atorvastatin injections for 3 weeks from week 8 of the atherogenic diet. Gene expression profiling was carried out with Affymetrix GeneChips. One-week atherogenic diet elevated 38 and inhibited 127 gene expressions, while 10-week atherogenic diet elevated 165 and inhibited 281 genes by more than twofold. Atorvastatin could restore 78.2% and 68%, respectively, of the genes to normal levels. Genes in the Insig (insulin-induced gene)-SREBP (sterol regulatory element binding proteins) pathway were mostly inhibited by atherogenic diet at week 1 but elevated at week 10. Of these, 65.2% were restored by atorvastatin. In conclusion, lipid homeostatic mechanism coped well with short-term atherogenic diet. However, when such a diet was prolonged, the mechanism was no longer effective but entered into a pathological state in which lipogenic genes, especially those in the Insig-SREBP pathway, were upregulated. Atorvastatin could restore changes in the Insig-SREBP pathway that were induced by the atherogenic diet.

Keywords: Atherogenic diet; Statin; Microarray; Insig-SREBP pathway

Document Type: Research article

DOI: http://dx.doi.org/10.3727/NO_DOI

Affiliations: 1: Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

Publication date: 2007-03-01

More about this publication?

• The Molecular and Cellular Biology area of Gene Expression covers all aspects of the gene including it structure, functions, and regulation in prokaryotes, eukaryotes, and viruses; molecular and cell biological aspects of cell growth and development, chromatin structure and function. These include topics such as DNA replication, DNA repair, gene transcription, transcriptional control, RNA processing, posttranscriptional control, oncogenes, molecular mechanisms of action of hormones, molecular mechanism of cellular differentiation, growth and development, protein synthesis, and posttranslational control.
  The Molecular and Cellular Neuroscience area of Gene Expression covers all aspects of gene expression as described but is devoted exclusively to the nervous system in health and disease. Topics include studies of neurogenesis, development, aging, and neurodegeneration. Complex neural systems, motor control, special senses, and higher cortical function, when viewed from the perspective of gene expression, are appropriate for the journal. Research related to molecular mechanisms of drug tolerance, dependence, and withdrawal are solicited. Manuscripts on state-of-the-art methods and protocols for molecular profiling of neuronal structure and function are welcome.

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