Intake of hydrolyzed casein is associated with reduced body fat accretion and enhanced phase II metabolism in obesity prone C57BL/6J mice.
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.
Department of Food Science, Aarhus University, Aarslev, Denmark.
Morten Rahr
MR
Clausen
Department of Food Science, Aarhus University, Aarslev, Denmark; State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
Xumin
X
Zhang
Department of Food Science, Aarhus University, Aarslev, Denmark.
Christian C
CC
Yde
Department of Food Science, Aarhus University, Aarslev, Denmark.
Ditte B
DB
Ditlev
National Institute of Nutrition and Seafood Research, Bergen, Norway; Department of Biology, University of Copenhagen, Copenhagen, Denmark.
Haldis H
HH
Lillefosse
National Institute of Nutrition and Seafood Research, Bergen, Norway; Department of Biology, University of Copenhagen, Copenhagen, Denmark.
Lise
L
Madsen
Department of Biology, University of Copenhagen, Copenhagen, Denmark.
Karsten
K
Kristiansen
National Institute of Nutrition and Seafood Research, Bergen, Norway.
Bjørn
B
Liaset
Department of Food Science, Aarhus University, Aarslev, Denmark.
Hanne C
HC
Bertram
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D002364:Caseins / Q000737:chemistry / Q000494:pharmacology*; D003545:Cysteine / Q000378:metabolism; D004198:Disease Susceptibility; D004435:Eating; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006868:Hydrolysis; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D050217:Metabolic Detoxication, Phase II; D055432:Metabolomics; D051379:Mice; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009765:Obesity / Q000378:metabolism* / Q000652:urine; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D002364:Caseins; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D016159:Tumor Suppressor Protein p53; D005947:Glucose; D003545:Cysteine