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Hepatic peroxisome proliferator activated receptor alpha (PPARα) is increased during mid- to late gestation in beef cows
Previous studies have shown that hepatic steroid inactivating enzymes, such as cytochrome P450 3A and uridine diphosphate-glucuronosyltransferase, partially regulate peripheral concentrations of estradiol-17β and progesterone during pregnancy. Several transcription factors have been implicated in regulating hepatic steroid inactivating enzymes in rodents and humans; however, few studies have examined these pathways in cattle. Therefore, our objective was to examine the effect of early to mid-gestation maternal dietary restriction followed by realimentation on the hepatic transcription factor PPARα. On d 30 of pregnancy, cows were assigned to dietary regimens: control (C; 100% NRC; n = 18) and restricted (R; 60% NRC; n = 34). On d 85 cows were slaughtered (C, n = 6 and R, n = 6), remained on control (CC; n = 12) and restricted (RR; n = 12), or were realimented to control (RC; n =11). On d 140 cows were slaughtered (CC, n = 6; RR, n = 6; RC, n = 5), remained on control (CCC, n = 6; RCC, n = 5), or were realimented to control (RRC, n = 6). On d 254 all remaining cows were slaughtered. At slaughter maternal liver samples were frozen for later determination of PPARα via enzyme-linked immunosorbent assay and cytochrome P450 1A (CYP1A) activities via a luminogenic substrate. Aldo-keto reductase 1C (AKR1C) activity was measured using the specific substrate 1-acenapthenol. Gestational day effects were tested among C, CC, and CCC cows, while dietary treatment effects were tested within a given slaughter day. Data were analyzed using the mixed procedure of SAS. Activity of PPARα was increased (P < 0.001) at d 140 and 254 of gestation vs. d 85. Activity of PPARα did not differ across dietary regimens at any given gestational day (P > 0.1). Activity of CYP1A did not differ across gestational day (P > 0.1) or across dietary regimens at any given gestational day (P > 0.1). Activity of AKR1C did not differ across gestational day (P > 0.2) or across dietary regimens at any given gestational day (P> 0.1). Interestingly, hepatic PPARα activity increased as gestation proceeded; however, maternal nutrient restriction did not affect hepatic PPARα. Therefore, PPARα induction during pregnancy may regulate hepatic energy metabolism during an important period of fetal growth and development irrespective of maternal nutrient restriction. Funded in part by USDA grant number 2009-65203-05812
Keywords: liver, pregnancy, steroid