Urinary loss of tricarboxylic acid cycle intermediates as revealed by metabolomics studies: an underlying mechanism to reduce lipid accretion by whey protein ingestion?
Whey protein intake is associated with the modulation of energy metabolism and altered body composition both in human subjects and in animals, but the underlying mechanisms are not yet elucidated. We fed obesity-prone C57BL/6J mice high-fat diets with either casein (HF casein) or whey (HF whey) for 6 weeks. At equal energy intake and apparent fat and nitrogen digestibility, mice fed HF whey stored less energy as lipids, evident both as lower white adipose tissue mass and as reduced liver lipids, compared with HF-casein-fed mice. Explorative analyses of 48 h urine, both by (1)H NMR and LC-MS metabolomic platforms, demonstrated higher urinary excretion of tricarboxylic acid (TCA) cycle intermediates citric acid and succinic acid (identified by both platforms), and cis-aconitic acid and isocitric acid (identified by LC-MS platform) in the HF whey, relative to in the HF-casein-fed mice. Targeted LC-MS analyses revealed higher citric acid and cis-aconitic acid concentrations in fed state plasma, but not in liver of HF-whey-fed mice. We propose that enhanced urinary loss of TCA cycle metabolites drain available substrates for anabolic processes, such as lipogenesis, thereby leading to reduced lipid accretion in HF-whey-fed compared to HF-casein-fed mice.
Department of Biology, University of Copenhagen , Ole Maaløes Vej 5, 2200 Copenhagen, Denmark.
Haldis H
HH
Lillefosse
Morten R
MR
Clausen
Christian C
CC
Yde
Ditte B
DB
Ditlev
Xumin
X
Zhang
Zhen-Yu
ZY
Du
Hanne C
HC
Bertram
Lise
L
Madsen
Karsten
K
Kristiansen
Bjørn
B
Liaset
D000156:Aconitic Acid / Q000652:urine; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002264:Carboxylic Acids / Q000652:urine*; D002364:Caseins / Q000008:administration & dosage / Q000494:pharmacology; D002853:Chromatography, Liquid; D019343:Citric Acid / Q000652:urine; D002952:Citric Acid Cycle; D059305:Diet, High-Fat; D007523:Isocitrates / Q000652:urine; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D013058:Mass Spectrometry; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D008810:Mice, Inbred C57BL; D008894:Milk Proteins / Q000008:administration & dosage / Q000494:pharmacology; D066244:Proton Magnetic Resonance Spectroscopy; D019802:Succinic Acid / Q000652:urine; D000067816:Whey Proteins
D002264:Carboxylic Acids; D002364:Caseins; D007523:Isocitrates; D008894:Milk Proteins; D000067816:Whey Proteins; D019343:Citric Acid; D000156:Aconitic Acid; C034219:isocitric acid; D019802:Succinic Acid