The Sterolgene v0 cDNA microarray: a systemic approach to studies of cholesterol homeostasis and drug metabolism

Režen, Tadeja; Juvan, Peter; Tacer, Klementina Fon; Kuzman, Drago; Roth, Adrian; Pompon, Denis; Aggerbeck, Lawrence P.; Meyer, Urs; Rozman, Damjana

doi:10.1186/1471-2164-9-76

Cited by 20 publications

(22 citation statements)

References 43 publications

(58 reference statements)

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“…It downregulated cholesterol biosynthesis as expected [70, 71]. In apoE-KO mice, a 1.25% cholesterol diet also regulated hepatic triglyceride metabolism through a suppression of Lipin1 and Lipin2 and by decreasing peroxisome proliferator-activated receptor-gamma coactivator 1 α , which upregulates the transcription of Lipin1 [72].…”

Section: Effect Of Dietary Fat Contentmentioning

confidence: 78%

The Use of Transcriptomics to Unveil the Role of Nutrients in Mammalian Liver

Osada

2013

ISRN Nutrition

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Liver is the organ primarily responding to diet, and it is crucial in determining plasma carbohydrate, protein, and lipid levels. In addition, it is mainly responsible for transformation of xenobiotics. For these reasons, it has been a target of transcriptomic analyses. In this review, we have covered the works dealing with the response of mammalian liver to different nutritional stimuli such as fasting/feeding, caloric restriction, dietary carbohydrate, cholesterol, fat, protein, bile acid, salt, vitamin, and oligoelement contents. Quality of fats or proteins has been equally addressed, and has the influence of minor dietary components. Other compounds, not purely nutritional as those represented by alcohol and food additives, have been included due to their relevance in processed food. The influence has been studied not only on mRNA but also on miRNA. The wide scope of the technology clearly reflects that any simple intervention has profound changes in many metabolic parameters and that there is a synergy in response when more compounds are included in the intervention. Standardized arrays to systematically test the same genes in all studies and analyzing data to establish patterns of response are required, particularly for RNA sequencing. Moreover, RNA is a valuable, easy-screening ally but always requires further confirmation.

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Section: Effect Of Dietary Fat Contentmentioning

confidence: 78%

The Use of Transcriptomics to Unveil the Role of Nutrients in Mammalian Liver

Osada

2013

ISRN Nutrition

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“…Cholesterol and its metabolites are also known to contribute to lipotoxicity and inflammation-mediated progression of NAFLD to NASH (Caballero et al, 2009). The cholesterol synthesis pathway responds to feedback regulation by cholesterol, TNF-α stimulation (Tacer et al, 2007), and xenobiotics, such as statins (Rezen et al, 2008, 2009; Rozman and Monostory, 2010), thus emphasizing the hepatic crosstalk between endobiotic and xenobiotic metabolism and inflammation. Endobiotics and xenobiotics activate various nuclear receptors and thus influence the expression of genes involved in the various hepatic metabolic pathways (Gao and Xie, 2010).…”

Section: Nafld and Drug Dispositionmentioning

confidence: 99%

Molecular Interactions between NAFLD and Xenobiotic Metabolism

Belič¹,

Zanger²,

Rozman³

2013

Front. Gene.

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Non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, is a complex multifactorial disease characterized by metabolic deregulations that include accumulation of lipids in the liver, lipotoxicity, and insulin resistance. The progression of NAFLD to non-alcoholic steatohepatitis and cirrhosis, and ultimately to carcinomas, is governed by interplay of pro-inflammatory pathways, oxidative stress, as well as fibrogenic and apoptotic cues. As the liver is the major organ of biotransformation, deregulations in hepatic signaling pathways have effects on both, xenobiotic and endobiotic metabolism. Several major nuclear receptors involved in the transcription and regulation of phase I and II drug metabolizing enzymes and transporters also have endobiotic ligands including several lipids. Hence, hepatic lipid accumulation in steatosis and NAFLD, which leads to deregulated activation patterns of nuclear receptors, may result in altered drug metabolism capacity in NAFLD patients. On the other hand, genetic and association studies have indicated that a malfunction in drug metabolism can affect the prevalence and severity of NAFLD. This review focuses on the complex interplay between NAFLD pathogenesis and drug metabolism. A better understanding of these relationships is a prerequisite for developing improved drug dosing algorithms for the pharmacotherapy of patients with different stages of NAFLD.

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“…Samples were hybridized to the Steroltalk v2 microarrays, in total 28 microarrays were used. Hybridization, washing and scanning of the Steroltalk slides were performed as described previously [12, 13]. …”

Section: Methodsmentioning

confidence: 99%

Acrolein‐induced dyslipidemia and acute‐phase response are independent of HMG‐CoA reductase

Conklin

Prough

Juvan

et al. 2011

Molecular Nutrition Food Res

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Scope Aldehydes are ubiquitous natural constituents of foods, water and beverages. Dietary intake represents the greatest source of exposure to acrolein and related aldehydes. Oral acrolein induces dyslipidemia acutely and chronically increases atherosclerosis in mice, yet the mechanisms are unknown. Because lipid synthesis and trafficking are largely under hepatic control, we examined hepatic genes in murine models of acute and chronic oral acrolein exposure. Methods and results Changes in hepatic gene expression were examined using a Steroltalk microarray. Acute acrolein feeding modified plasma and hepatic proteins and increased plasma triglycerides within 15 min. By 6h, acrolein altered hepatic gene expression including Insig1, Insig2 and Hmgcr genes and stimulated an acute phase response (APR) with up-regulation of serum amyloid A genes (Saa) and systemic hypoalbuminemia. To test if decreased HMG-CoA reductase activity could modify acrolein-induced dyslipidemia or the APR, mice were pretreated with simvastatin. Statin treatment, however, did not alter acrolein-induced dyslipidemia or hypoalbuminemia associated with an APR. Few hepatic genes were dysregulated by chronic acrolein feeding in apoE-null mice. These studies confirmed that acute acrolein exposure altered expression of hepatic genes involved with lipid synthesis and trafficking and APR, and thus, indicated a hepatic locus of acrolein-induced dyslipidemia and APR that was independent of HMG CoA-reductase. Conclusion Dietary intake of acrolein could contribute to cardiovascular disease risk by disturbing hepatic function.

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The Sterolgene v0 cDNA microarray: a systemic approach to studies of cholesterol homeostasis and drug metabolism

Cited by 20 publications

References 43 publications

The Use of Transcriptomics to Unveil the Role of Nutrients in Mammalian Liver

The Use of Transcriptomics to Unveil the Role of Nutrients in Mammalian Liver

Molecular Interactions between NAFLD and Xenobiotic Metabolism

Acrolein‐induced dyslipidemia and acute‐phase response are independent of HMG‐CoA reductase

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