Glycomacropeptide, a low-phenylalanine protein isolated from cheese whey, supports growth and attenuates metabolic stress in the murine model of phenylketonuria.
Phenylketonuria (PKU) is caused by a mutation in the phenylalanine (phe) hydroxylase gene and requires a low-phe diet plus amino acid (AA) formula to prevent cognitive impairment. Glycomacropeptide (GMP) contains minimal phe and provides a palatable alternative to AA formula. Our objective was to compare growth, body composition, and energy balance in Pah(enu2) (PKU) and wild-type mice fed low-phe GMP, low-phe AA, or high-phe casein diets from 3-23 wk of age. The 2 × 2 × 3 design included main effects of genotype, sex, and diet. Fat and lean mass were assessed by dual-energy X-ray absorptiometry, and acute energy balance was assessed by indirect calorimetry. PKU mice showed growth and lean mass similar to wild-type littermates fed the GMP or AA diets; however, they exhibited a 3-15% increase in energy expenditure, as reflected in oxygen consumption, and a 3-30% increase in food intake. The GMP diet significantly reduced energy expenditure, food intake, and plasma phe concentration in PKU mice compared with the casein diet. The high-phe casein diet or the low-phe AA diet induced metabolic stress in PKU mice, as reflected in increased energy expenditure and intake of food and water, increased renal and spleen mass, and elevated plasma cytokine concentrations consistent with systemic inflammation. The low-phe GMP diet significantly attenuated these adverse effects. Moreover, total fat mass, %body fat, and the respiratory exchange ratio (CO(2) produced/O(2) consumed) were significantly lower in PKU mice fed GMP compared with AA diets. In summary, GMP provides a physiological source of low-phe dietary protein that promotes growth and attenuates the metabolic stress induced by a high-phe casein or low-phe AA diet in PKU mice.
Department of Nutritional Sciences, University of Wisconsin-Madison, 53706, USA.
Patrick
P
Solverson
Sangita G
SG
Murali
Adam S
AS
Brinkman
David W
DW
Nelson
Murray K
MK
Clayton
Chi-Liang Eric
CL
Yen
Denise M
DM
Ney
D015502:Absorptiometry, Photon; D000596:Amino Acids / Q000097:blood / Q000494:pharmacology; D000818:Animals; D001823:Body Composition / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002364:Caseins / Q000494:pharmacology*; D002611:Cheese / Q000032:analysis*; D016207:Cytokines / Q000097:blood; D004032:Diet; D018753:Diet, Protein-Restricted; D004734:Energy Metabolism / Q000187:drug effects; D006128:Growth / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D010641:Phenotype; D010661:Phenylketonurias / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000187:drug effects / Q000254:growth & development / Q000473:pathology; D013163:Splenomegaly / Q000139:chemically induced / Q000473:pathology
D000596:Amino Acids; D002364:Caseins; D016207:Cytokines; D010446:Peptide Fragments; C065989:caseinomacropeptide