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Differential expression of intestinal genes in opossums with high and low responses to dietary cholesterol.

ABSTRACT: High and low responding opossums (Monodelphis domestica) differ in their plasma very low density lipoprotein and low density lipoprotein (VLDL+LDL) cholesterol concentrations when they consume a high cholesterol diet, which is due in part to absorption of a higher percentage of dietary cholesterol in high responders. We compared the expression of a set of genes that influence cholesterol absorption in high and low responders fed a basal or a high cholesterol and low fat (HCLF) diet. Up-regulation of the ABCG5, ABCG8, and IBABP genes by the HCLF diet in high and low responders may reduce cholesterol absorption to maintain cholesterol homeostasis. Differences in expression of the phospholipase genes (PLA2 and PLB) and phospholipase activity were associated with differences in cholesterol absorption when opossums were fed cholesterol-enriched diets. Higher PLA2 and PLB mRNA levels and higher phospholipase activity may increase cholesterol absorption in high responders by enhancing the release of cholesterol from bile salt micelles for uptake by intestinal cells.

SUBMITTER: Chan J

PROVIDER: S-EPMC2915800 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Differential expression of intestinal genes in opossums with high and low responses to dietary cholesterol.

Chan Jeannie J Kushwaha Rampratap S RS Vandeberg Jane F JF Gluhak-Heinrich Jelica J Vandeberg John L JL

Journal of nutrition and metabolism 20091123

High and low responding opossums (Monodelphis domestica) differ in their plasma very low density lipoprotein and low density lipoprotein (VLDL+LDL) cholesterol concentrations when they consume a high cholesterol diet, which is due in part to absorption of a higher percentage of dietary cholesterol in high responders. We compared the expression of a set of genes that influence cholesterol absorption in high and low responders fed a basal or a high cholesterol and low fat (HCLF) diet. Up-regulatio ...[more]

PMID: 20721351

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Project description:BackgroundDysregulation of microRNA (miRNA) expression has been implicated in molecular genetic events leading to the progression and development of atherosclerosis. We hypothesized that miRNA expression profiles differ between baboons with low and high serum low-density lipoprotein cholesterol (LDL-C) concentrations in response to diet, and that a subset of these miRNAs regulate genes relevant to dyslipidemia and risk of atherosclerosis.ResultsUsing Next Generation Illumina sequencing methods, we sequenced hepatic small RNA libraries from baboons differing in their LDL-C response to a high-cholesterol, high-fat (HCHF) challenge diet (low LDL-C, n?=?3; high LDL-C, n?=?3), resulting in 517 baboon miRNAs: 490 were identical to human miRNAs and 27 were novel. We compared miRNA expression profiles from liver biopsies collected before and after the challenge diet and observed that HCHF diet elicited expression of more miRNAs compared to baseline (chow) diet for both low and high LDL-C baboons. Eighteen miRNAs exhibited differential expression in response to HCHF diet in high LDL-C baboons compared to 10 miRNAs in low LDL-C baboons. We used TargetScan/Base tools to predict putative miRNA targets; miRNAs expressed in high LDL-C baboons had significantly more gene targets than miRNAs expressed in low LDL-C responders. Further, we identified miRNA isomers and other non-coding RNAs that were differentially expressed in response to the challenge diet in both high LDL-C and low LDL-C baboons.ConclusionsWe sequenced and annotated baboon liver miRNAs from low LDL-C and high LDL-C responders using high coverage Next Gen sequencing methods, determined expression changes in response to a HCHF diet challenge, and predicted target genes regulated by the differentially expressed miRNAs. The identified miRNAs will enrich the database for non-coding small RNAs including the extent of variation in these sequences. Further, we identified other small non-coding RNAs differentially expressed in response to diet. Our discovery of differentially expressed baboon miRNAs in response to a HCHF diet challenge that differ by LDL-C phenotype is a fundamental step in understating the role of non-coding RNAs in dyslipidemia.

Dataset Information

Differential expression of intestinal genes in opossums with high and low responses to dietary cholesterol.

Publications

Differential expression of intestinal genes in opossums with high and low responses to dietary cholesterol.

Similar Datasets

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