Consumption of a high-fat diet during pregnancy changes the expression of cytochrome P450 in the livers of infant male mice.
It has been recently reported that the consumption of a high-fat diet during pregnancy exerts various effects on fetuses and newborn mice. The purpose of this study was to determine the effects of a high-fat diet during pregnancy on the expression of cytochrome P450 (CYP) in the livers of offspring. Mouse dams were fed a high-fat diet during pregnancy from the time of conception. After their birth, the newborn mice were fed a normal diet until 12 weeks of age. In the livers of the infant male mice that consumed a high-fat diet, the protein expression of CYP3A and CYP2C was decreased, and the protein expression of CYP1A and CYP2E was increased at 6 and 12 weeks of age. However, almost no changes were observed in the CYP proteins at 6 and 12 weeks of age in the livers of the infant female mice that consumed a high-fat diet. The amount of pregnane X receptor (PXR) translocated into the nucleus was reduced in the livers of infant male mice that consumed a high-fat diet. However, there was neither an increase in tumor necrosis factor-α or interleukin-1β nor a decrease in lithocholic acid. These data suggested that CYP3A and CYP2C might decrease as a result of the decrease in the amount of nuclear PXR in infant male mice that consumed a high-fat diet. The results of this study suggested that the consumption of a high-fat diet by pregnant mothers may be one explanation for individual differences in pharmacokinetics.
Department of Clinical Pharmacokinetics, Hoshi University, 2-4-41 Ebara, Tokyo 142-8501, Japan.
Masataka
M
Tajima
Nobutomo
N
Ikarashi
Takehiro
T
Okaniwa
Yukari
Y
Imahori
Kanako
K
Saruta
Takahiro
T
Toda
Makoto
M
Ishii
Yoshikazu
Y
Tanaka
Yoshiaki
Y
Machida
Wataru
W
Ochiai
Harumi
H
Yamada
Kiyoshi
K
Sugiyama
D000818:Animals; D000831:Animals, Newborn; D001441:Bacteroides fragilis / Q000235:genetics / Q000302:isolation & purification; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004269:DNA, Bacterial / Q000032:analysis; D059305:Diet, High-Fat; D005243:Feces / Q000382:microbiology; D005260:Female; D053583:Interleukin-1beta / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D000077297:Pregnane X Receptor; D011297:Prenatal Exposure Delayed Effects; D011987:Receptors, Steroid / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D004269:DNA, Bacterial; D053583:Interleukin-1beta; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D003577:Cytochrome P-450 Enzyme System