Oligonucleotide Microarray Analysis of Dietary-Induced Hyperlipidemia Gene Expression Profiles in Miniature Pigs

Abstract

BackgroundHyperlipidemia animal models have been established, but complete gene expression profiles of the transition from normal lipid levels have not been obtained. Miniature pigs are useful model animals for gene expression studies on dietary-induced hyperlipidemia because they have a similar anatomy and digestive physiology to humans, and blood samples can be obtained from them repeatedly.MethodologyTwo typical dietary treatments were used for dietary-induced hyperlipidemia models, by using specific pathogen-free (SPF) Clawn miniature pigs. One was a high-fat and high-cholesterol diet (HFCD) and the other was a high-fat, high-cholesterol, and high-sucrose diet (HFCSD). Microarray analyses were conducted from whole blood samples during the dietary period and from white blood cells at the end of the dietary period to evaluate the transition of expression profiles of the two dietary models.Principal FindingsVariations in whole blood gene expression intensity within the HFCD or the HFCSD group were in the same range as the controls provide with normal diet at all periods. This indicates uniformity of dietary-induced hyperlipidemia for our dietary protocols. Gene ontology- (GO) based functional analyses revealed that characteristics of the common changes between HFCD and HFCSD were involved in inflammatory responses and reproduction. The correlation coefficient between whole blood and white blood cell expression profiles at 27 weeks with the HFCSD diet was significantly lower than that of the control and HFCD diet groups. This may be due to the effects of RNA originating from the tissues and/or organs.ConclusionsNo statistically significant differences in fasting plasma lipids and glucose levels between the HFCD and HFCSD groups were observed. However, blood RNA analyses revealed different characteristics corresponding to the dietary protocols. In this study, whole blood RNA analyses proved to be a useful tool to evaluate transitions in dietary-induced hyperlipidemia gene expression profiles in miniature pigs.

Whole Blood Transcriptomics Is Relevant to Identify Molecular Changes in Response to Genetic Selection for Feed Efficiency and Nutritional Status in the Pig

“…Despite the low number of genes DE in response to the HF compared with the LF diet, the current study highlighted differences in the expression of genes related to the immune system and lipid metabolism as shown reported in PBMC of miniature pigs fed a hyperlipidic diet versus hyperlipidic and hyperglucidic diet for 27 weeks [ 37 ]. Overexpressed genes in pigs fed the HF diet were mainly involved in host defense mechanism ( PR39 , PMAP-23 , CD5L , PGLYRP1 ).…”

Dietary energy source largely affects tissue fatty acid composition but has minor influence on gene transcription in Iberian pigs1

“…To our knowledge, this is the first work in which the effect of porcine diet FA composition on gene expression has been studied with a transcriptome approach. In fact very few nutrigenomic studies have been performed in this animal species and microarray tools have been scarcely used and mainly limited to studies using pigs as animal models for human issues or diseases, for example, the study of the transcriptional effects of dietary-induced hyperlipidemia or formula feeding in neonates (Takahashi et al, 2012;Ronis et al, 2011). In contrast with humans and rats, the porcine adipose tissue is considered by far the main lipogenic tissue (O'Hea and Leveille, 1969;Gondret et al, 2001) and therefore this tissue was selected for our global gene expression study.…”

Whole Blood RNA Analysis, Aging and Disease

“…In contrast, GO terms related to the repair of damaged organs, including translation (GO: 0006412), positive regulation of growth rate (GO: 0040010), and growth (GO: 004007), showed low correlation coefficients. We, therefore, conclude that the difference in the gene expression profiles between the whole blood and white blood cells are not only caused by differences in experimental protocols, but also by differences in RNA origin [34].…”