Dataset Information

Intake of hydrolyzed casein is associated with reduced body fat accretion and enhanced phase II metabolism in obesity prone C57BL/6J mice.

ABSTRACT: The amount and form of dietary casein have been shown to affect energy metabolism and lipid accumulation in mice, but the underlying mechanisms are not fully understood. We investigated 48 hrs urinary metabolome, hepatic lipid composition and gene expression in male C57BL/6J mice fed Western diets with 16 or 32 energy% protein in the form of extensively hydrolyzed or intact casein. LC-MS based metabolomics revealed a very strong impact of casein form on the urinary metabolome. Evaluation of the discriminatory metabolites using tandem mass spectrometry indicated that intake of extensively hydrolyzed casein modulated Phase II metabolism associated with an elevated urinary excretion of glucuronic acid- and sulphate conjugated molecules, whereas glycine conjugated molecules were more abundant in urine from mice fed the intact casein diets. Despite the differences in the urinary metabolome, we observed no differences in hepatic expression of genes involved in Phase II metabolism, but it was observed that expression of Abcc3 encoding ATP binding cassette c3 (transporter of glucuronic acid conjugates) was increased in livers of mice fed hydrolyzed casein. As glucuronic acid is derived from glucose and sulphate is derived from cysteine, our metabolomic data provided evidence for changes in carbohydrate and amino acid metabolism and we propose that this modulation of metabolism was associated with the reduced glucose and lipid levels observed in mice fed the extensively hydrolyzed casein diets.

SUBMITTER: Clausen MR

PROVIDER: S-EPMC4349863 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Intake of hydrolyzed casein is associated with reduced body fat accretion and enhanced phase II metabolism in obesity prone C57BL/6J mice.

Clausen Morten Rahr MR Zhang Xumin X Yde Christian C CC Ditlev Ditte B DB Lillefosse Haldis H HH Madsen Lise L Kristiansen Karsten K Liaset Bjørn B Bertram Hanne C HC

PloS one 20150304 3

The amount and form of dietary casein have been shown to affect energy metabolism and lipid accumulation in mice, but the underlying mechanisms are not fully understood. We investigated 48 hrs urinary metabolome, hepatic lipid composition and gene expression in male C57BL/6J mice fed Western diets with 16 or 32 energy% protein in the form of extensively hydrolyzed or intact casein. LC-MS based metabolomics revealed a very strong impact of casein form on the urinary metabolome. Evaluation of the ...[more]

PMID: 25738501

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Project description:A high caloric diet, in conjunction with low levels of physical activity, promotes obesity. Many studies are available regarding the relation between dietary saturated fats and the etiology of obesity, but most focus on liver, muscle and white adipose tissue. Furthermore, the majority of transcriptomic studies seek to identify linear effects of an external stimulus on gene expression, although such an assumption does not necessarily hold. Our work assesses the dose-dependent effects of dietary fat intake on differential gene expression in the proximal, middle and distal sections of the small intestine in C57BL/6J mice. Gene expression is analyzed in terms of either linear or nonlinear responses to fat intake.The highest number of differentially expressed genes was observed in the middle section. In all intestine sections, most of the identified processes exhibited a linear response to increasing fat intake. The relative importance of logarithmic and exponential responses was higher in the proximal and distal sections, respectively. Functional enrichment analysis highlighted a constantly linear regulation of acute-phase response along the whole small intestine, with up-regulation of Serpina1b. The study of gene expression showed that exponential down-regulation of cholesterol transport in the middle section is coupled with logarithmic up-regulation of cholesterol homeostasis. A shift from linear to exponential response was observed in genes involved in the negative regulation of caspase activity, from middle to distal section (e.g., Birc5, up-regulated).The transcriptomic signature associated with inflammatory processes preserved a linear response in the whole small intestine (e.g., up-regulation of Serpina1b). Processes related to cholesterol homeostasis were particularly active in the middle small intestine and only the highest fat intake down-regulated cholesterol transport and efflux (with a key role played by the down-regulation of ATP binding cassette transporters). Characterization of nonlinear patterns of gene expression triggered by different levels of dietary fat is an absolute novelty in intestinal studies. This approach helps identifying which processes are overloaded (i.e., positive, logarithmic regulation) or arrested (i.e., negative, exponential regulation) in response to excessive fat intake, and can shed light on the relationships linking lipid intake to obesity and its associated molecular disturbances.

Dataset Information

Intake of hydrolyzed casein is associated with reduced body fat accretion and enhanced phase II metabolism in obesity prone C57BL/6J mice.

Publications

Intake of hydrolyzed casein is associated with reduced body fat accretion and enhanced phase II metabolism in obesity prone C57BL/6J mice.

Similar Datasets

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