Feeding conditions control the expression of genes involved in sterol metabolism in peripheral blood mononuclear cells of normoweight and diet-induced (cafeteria) obese rats☆
Received 24 June 2009; received in revised form 24 September 2009; accepted 1 October 2009. published online 22 February 2010. Corrected Proof
Abstract
Peripheral blood mononuclear cells (PBMC) are easily obtainable cells from blood whose gene expression profiles have been proven to be highly robust in distinguishing a disease state from healthy state. Sterol metabolism is of physiological importance, and although its nutritional response in liver has been described, it is poorly studied in PBMC. To examine if PBMC sterol metabolism reflects diet-induced physiological responses, we analysed the whole genome gene expression response of PBMC and focused on sterol metabolism-related genes affected by different feeding conditions (ad libitum feeding, fasting, and refeeding) in normoweight (control) rats and in diet-induced (cafeteria) obese rats.
Our results of microarray analysis show that, in control rats, 21 genes involved in sterol metabolism were regulated by the different feeding conditions, whereas in cafeteria-obese rats, only seven genes showed a changed expression. Most of the genes identified were classified into three pathways: sterol biosynthesis, cholesterol transport and uptake and sterol signaling. The expression profile of these genes was similar to that previously described for liver, decreasing in response to fasting conditions and recovering the levels found in fed animals after 6-h-refeeding. In addition, our data and the comparable expression pattern of sterol metabolism-related genes between PBMC and liver suggest similar sterol regulatory element-binding protein-mediated regulatory mechanisms in response to feeding conditions in both tissues.
In conclusion, the expression of genes involved in sterol metabolism is highly controlled by feeding conditions in PBMC of control rats, but this control is impaired in cafeteria-obese animals. The pathophysiological significance of this impairment requires further investigation.
aLaboratory of Molecular Biology, Nutrition and Biotechnology, Universitat de les Illes Balears and CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), E-07122, Palma de Mallorca, Spain
bHuman and Animal Physiology, Wageningen University, 6708 PG, Wageningen, The Netherlands
cFood Bioactives Group, RIKILT – Institute of Food Safety, 6708 PD, Wageningen, The Netherlands
Corresponding author. Lab. Molecular Biology, Nutrition and Biotechnology, Universitat de les Illes Balears, Cra. Valldemossa km 7.5. E-07122-Palma de Mallorca, Spain. Tel.: +34 971173170; fax: +34 971173426.
☆ CIBER de Fisiopatología de la Obesidad y Nutrición is an initiative of the ISCIII. This work was supported by the Spanish Government (Ministerio de Educación y Ciencia, AGL2006-04887/ALI and AGL2009-11277/ALI). Our laboratory is a member of the European Research Network of Excellence NuGO (The European Nutrigenomics Organization, EU Contract: FOOD-CT-2004-506360 NUGO). Antoni Caimari is a recipient of a fellowship from the Government of the Balearic Islands.
ABSTRACT