Unknown,Transcriptomics,Genomics,Proteomics

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Dose-dependent effects of dietary fat on development of obesity in relation to intestinal differential gene expression in C57BL/6J mice

ABSTRACT: Excessive intake of dietary fat is known to be a contributing factor in the development of obesity. In this study, we determined the dose-dependent effects of dietary fat on the development of this metabolic condition with a focus on changes in gene expression in the small intestine. C57BL/6J mice were fed diets with either 10, 20, 30 or 45 energy% (E%) derived from fat for four weeks (n=10 mice/diet). We found a significant higher weight gain in mice fed the 30E% and 45E% fat diet compared to mice on the control diet. These data indicate that the main shift towards an obese phenotype lies between a 20E% and 30E% dietary fat intake. Analysis of differential gene expression in the small intestine showed a fat-dose dependent gradient in differentially expressed genes, with the highest numbers in mice fed the 45E% fat diet. The main shift in fat-induced differential gene expression was found between the 30E% and 45E% fat diet. Furthermore, approximately 70% of the differentially expressed genes were regulated in a fat-dose dependent manner. Many of these genes were involved in lipid metabolism-related processes and were already differentially expressed on a 30E% fat diet. Taken together, we conclude that up to 20E% of dietary fat, the small intestine has an effective ‘buffer capacity’ for fat handling. From 30E% of dietary fat, a switch towards an obese phenotype is triggered. We further speculate that especially fat-dose dependently regulated lipid metabolism-related genes are involved in development of obesity. The proximal, middle, and distal parts of the intestine of mice fed 10, 20, 30, or 45E% dietary fat were analyzed. 10 replicates each.

ORGANISM(S): Mus musculus

SUBMITTER: Guido Hooiveld

PROVIDER: E-GEOD-26300 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Dose-dependent effects of dietary fat on development of obesity in relation to intestinal differential gene expression in C57BL/6J mice.

de Wit Nicole J W NJ Boekschoten Mark V MV Bachmair Eva-Maria EM Hooiveld Guido J E J GJ de Groot Philip J PJ Rubio-Aliaga Isabel I Daniel Hannelore H Müller Michael M

PloS one 20110425 4

Excessive intake of dietary fat is known to be a contributing factor in the development of obesity. In this study, we determined the dose-dependent effects of dietary fat on the development of this metabolic condition with a focus on changes in gene expression in the small intestine. C57BL/6J mice were fed diets with either 10, 20, 30 or 45 energy% (E%) derived from fat for four weeks (n = 10 mice/diet). We found a significant higher weight gain in mice fed the 30E% and 45E% fat diet compared to ...[more]

PMID: 21547079

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Project description:By regulating digestion and absorption of nutrients and providing a barrier against the external environment the intestine provides a crucial contribution to the maintenance of health. To what extent aging-related changes in the intestinal system contribute to the impaired health of the aging body is still under debate. Young (4 months) and old (21 months) male C57BL/6J mice were fed a control low-fat (10E%) or a high-fat diet (45E%) for 2 weeks. During the intervention gross energy intake and energy excretion in the feces were measured. After sacrifice the small and large intestine were isolated whereby the small intestine was divided in three equal parts. Of each of the isolated segments Swiss rolls were prepared for histological analysis and the luminal content was isolated to examine alterations in the microflora with 16S rRNA Q-PCR. Furthermore, mucosal scrapings were isolated from each segment to determine differential gene expression by microarray analysis and global DNA methylation by pyrosequencing. Digestible energy intake was similar between the two age groups on both the control and the high-fat diet implying that macronutrient metabolism is not affected in 21-month-old mice. This observation was supported by the fact that the microarray analysis on RNA from intestinal scrapings showed no marked changes in expression of genes involved in metabolic processes. Decreased expression of Cubilin was observed in the intestine of 21-month-old mice, which might contribute to aging-induced vitamin B12 deficiency. Furthermore, microarray data analysis revealed enhanced expression of a high number of genes involved in immune response and inflammation in the colon, but not in the small intestine of the 21-month-old mice. Aging-induced global hypomethylation was observed in the colon and the distal part of the small intestine, but not in the first two sections of the small intestine. In 21-month old mice the most pronounced effects of aging was observed in the colon, limited changes were observed in the small intestine. Young (4 months) and old (21 months) C57BL/6J mice were fed a low-fat (10E%) diet or high-fat (45%E) diet for 2 weeks. After the diet intervention period, the animals were killed and scrapings were made of the proximal, middle and distal part of the small intestine. Total RNA was isolated, pooled and subjected to gene expression profiling.

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Dataset Information

Dose-dependent effects of dietary fat on development of obesity in relation to intestinal differential gene expression in C57BL/6J mice

Publications

Dose-dependent effects of dietary fat on development of obesity in relation to intestinal differential gene expression in C57BL/6J mice.

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