Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Benefits of a 6 week supplementation of sebacic acid on a mouse model of type 2 diabetes (db/db mice)

ABSTRACT: This study aimed at investigating the impact of chronic ingestion of sebacic acid (SA), a 10 carbons medium-chain dicarboxylic acid, on glycemic control in a mouse model of type 2 diabetes (db/db mice). Three groups of 15 mice were fed for 6 weeks either a chow diet (Ctrl), or a chow diet supplemented with 1.5% or 15% (SA1.5% and SA15% resp.) energy from SA. Fasting glycemia was measured once a week and HbA1c before and after supplementation. An oral glucose tolerance test (OGTT) was performed at the end of the supplementation. Gene expression was determined by transcriptomic analysis on the liver of the Ctrl and SA15% groups. Results-After 42 days of supplementation, fasting glycemia and HbA1c were ~70% and ~25% lower in the SA15% group compared to other groups showing a beneficial effect of SA on hyperglycemia. During OGTT, blood glucose area under the curve (AUC) was reduced after SA15% compared to other groups. This effect was associated with a tendency for an improved insulin response. In the liver, Pck1 and FBP mRNA were statistically decreased in the SA15% compared to Ctrl suggesting a reduced hepatic glucose output induced by SA. Conclusions-Dietary supplementation of SA largely improves glycemic control in a mouse model of type 2 diabetes. This beneficial effect may be due (1) to a reduced hepatic glucose output resulting from transcriptional down regulation of key gluconeogenesis genes and (2) to an improved glucose induced-insulin secretion. Microarray analysis of 6-8 wk old male BKS.Cg-m+/+Leprdb/J 000642 db/db mice. 2 groups. n=15/group: 1) Control group. 2) Sebacic acid high dose group - 15% (77.6g/kg food, â??9g/kg body weight per day).

ORGANISM(S): Mus musculus

SUBMITTER: Mathieu Membrez

PROVIDER: E-GEOD-21083 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Six weeks' sebacic acid supplementation improves fasting plasma glucose, HbA1c and glucose tolerance in db/db mice.

Membrez M M Chou C J CJ Raymond F F Mansourian R R Moser M M Monnard I I Ammon-Zufferey C C Mace K K Mingrone G G Binnert C C

Diabetes, obesity & metabolism 20101201 12

<h4>Aim</h4>To investigate the impact of chronic ingestion of sebacic acid (SA), a 10-carbon medium-chain dicarboxylic acid, on glycaemic control in a mouse model of type 2 diabetes (T2D).<h4>Methods</h4>Three groups of 15 db/db mice were fed for 6 weeks either a chow diet (Ctrl) or a chow diet supplemented with 1.5 or 15% (SA(1.5%) and SA(15%) , respectively) energy from SA. Fasting glycaemia was measured once a week and HbA1c before and after supplementation. An oral glucose tolerance test (OG ...[more]

PMID: 20977585

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Project description:The mechanisms by which the placenta adapts to exogenous stimuli to create a stable and healthy environment for the growing fetus are not well known. Low oxygen tension and sub-optimal vitamin D levels influence placental function and both are associated with preeclampsia, a condition associated with altered development of placental trophoblast. We hypothesized that oxygen tension, vitamin D levels, or both affect villous trophoblast by modulation of gene expression through DNA methylation. To test this we used the Illumina Infinium Human Methylation 450 BeadChip array to compare the DNA methylation profile of primary cultures of human cytotrophoblasts and syncytiotrophoblasts under three oxygen tensions and three vitamin D levels. We found no effect on global DNA methylation by either treatment, but a limited set of loci became hypermethylated in cytotrophoblasts exposed for 24 hours to 1% oxygen, as compared to the same cells exposed to 8% or 20% oxygen. Vitamin D levels had no detectable effect on methylation profiles in either trophoblast type. Hypermethylation with low oxygen tension was independently confirmed by bisulfite-pyrosequencing in a subset of functionally important genes including CP, ITGA5, SOD2, XDH and ZNF2. Intriguingly, 70 out of the 147 hypoxia-associated CpGs, overlapped with CpG sites that become hypomethylated upon differentiation of cytotrophoblasts into syncytiotrophoblasts. Furthermore, the preponderance of altered sites was located at AP-1 binding sites. We suggest that AP-1 expression is triggered by hypoxia and interacts with DNA methyltransferases (DNMTs) to target methylation at specific sites in the genome, thus causing suppression of the associated genes that are responsible for differentiation of villous cytotrophoblast to syncytiotrophoblast. RNA from cytotrophoblast from 2 placentas exposed to 3 different conditions of hypoxia (1%,8%,20%) and treated with 3 levels of vitamin D were run on the Illumina HT-12v4 Expression Array

Dataset Information

Benefits of a 6 week supplementation of sebacic acid on a mouse model of type 2 diabetes (db/db mice)

Publications

Six weeks' sebacic acid supplementation improves fasting plasma glucose, HbA1c and glucose tolerance in db/db mice.

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