Rapid neonatal weight gain in rats results in a renal ubiquinone (CoQ) deficiency associated with premature death.
We have recently reported that maternal dietary imbalance during pregnancy and lactation can reduce the lifespan of offspring. Rats that were growth restricted in utero by maternal protein restriction and underwent rapid weight gain when suckled by control fed dams died earlier than animals whose mothers were fed a control diet throughout pregnancy and lactation. We demonstrate here that mitochondrial abnormalities and DNA damage occur in the kidney of offspring who die prematurely. We have established by direct measurement and by in vitro supplementation that mitochondrial abnormalities occur because of a functional deficit of the mitochondrial cofactor coenzyme Q9 (CoQ9). These data provide molecular insight into the association between maternal nutrition and determination of offspring lifespan, and identify, a potential dietary intervention to prevent detrimental consequences of imbalanced maternal nutrition.
Neurochemistry Division, Institute of Neurology, UCL, London WC1N 3BG, UK.
Piran
P
Shelley
Jane
J
Tarry-Adkins
Malgorzata
M
Martin-Gronert
Lucilla
L
Poston
Simon
S
Heales
John
J
Clark
Susan
S
Ozanne
Josie
J
McConnell
D000818:Animals; D000831:Animals, Newborn; D003067:Coenzymes / Q000172:deficiency; D004249:DNA Damage; D018753:Diet, Protein-Restricted; D004195:Disease Models, Animal; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D007668:Kidney / Q000201:enzymology / Q000378:metabolism*; D007774:Lactation; D008136:Longevity; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D039401:Prenatal Nutritional Physiological Phenomena; D051381:Rats; D017208:Rats, Wistar; D016615:Telomere / Q000378:metabolism; D013997:Time Factors; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000172:deficiency*; D015430:Weight Gain
D003067:Coenzymes; D045222:Electron Transport Chain Complex Proteins; D014451:Ubiquinone; C024989:coenzyme Q10; C030571:ubiquinone 9