Borel Patrick, Troadec Romane, Damiani Morgane, Halimi Charlotte, Nowicki Marion, Guichard Philippe, Couturier Charlene, Margier Marielle, Mounien Lourdes, Grino Michel, Reboul Emmanuelle, Landrier Jean-François, Desmarchelier Charles
Center for CardioVascular and Nutrition Research (C2VN), Faculté de Médecine, INRAE, INSERM, Aix Marseille Univ, 27, boulevard Jean Moulin, 13005, Marseille, France.
Institut Universitaire de France (IUF), Marseille, France.
Eur J Nutr. 2023 Mar;62(2):633-646. doi: 10.1007/s00394-022-03019-2. Epub 2022 Sep 30.
Offspring from rats reared on a control (C) or a VA-deficient (D) diet from 6 weeks before mating until offspring weaning, i.e., 7 weeks after mating, were themselves reared on a C or D diet for 19 weeks, resulting in the following groups: C-C (parents fed C-offspring fed C), D-C, C-D and D-D. VA concentrations were measured in plasma and liver. β-Carotene bioavailability and its intestinal conversion rate to VA, as well as vitamin D and E bioavailability, were assessed after gavages with these vitamins. Expression of genes involved in VA metabolism and transport was measured in intestine and liver.
C-D and D-D had no detectable retinyl esters in their liver. Retinolemia, hepatic retinol concentrations and postprandial plasma retinol response to β-carotene gavage were higher in D-C than in C-C. Intestinal expression of Isx was abolished in C-D and D-D and this was concomitant with a higher expression of Bco1, Scarb1, Cd36 and Lrat in males receiving a D diet as compared to those receiving a C diet. β-Carotene, vitamin D and E bio-availabilities were lower in offspring receiving a D diet as compared to those receiving a C diet.
A VA-deficient diet during the perinatal period modifies the metabolism of this vitamin in the offspring. Isx-mediated regulation of Bco1 and Scarb1 expression exists only in males severely deficient in this vitamin. Severe VA deficiency impairs β-carotene and vitamin D and E bioavailability.
1)验证围产期维生素A(VA)对VA代谢进行编程的假说,并更好地理解VA代谢的肠道调节机制。
将从交配前6周开始直至后代断奶(即交配后7周)期间分别以对照(C)或VA缺乏(D)饮食饲养的大鼠后代,自身再以C或D饮食饲养19周,从而形成以下几组:C-C组(亲代喂C饮食 - 子代喂C饮食)、D-C组、C-D组和D-D组。测定血浆和肝脏中的VA浓度。在用这些维生素灌胃后,评估β-胡萝卜素的生物利用度及其向VA的肠道转化率,以及维生素D和E的生物利用度。测定肠道和肝脏中参与VA代谢和转运的基因表达。
C-D组和D-D组的肝脏中未检测到视黄酯。D-C组的血清视黄醇水平、肝脏视黄醇浓度以及餐后血浆视黄醇对β-胡萝卜素灌胃的反应均高于C-C组。C-D组和D-D组中Isx的肠道表达消失,并且与接受C饮食的雄性相比,接受D饮食的雄性中Bco1、Scarb1、Cd36和Lrat的表达更高。与接受C饮食的后代相比,接受D饮食的后代中β-胡萝卜素、维生素D和E的生物利用度较低。
围产期VA缺乏饮食会改变后代中这种维生素的代谢。Isx介导的对Bco1和Scarb1表达的调节仅存在于严重缺乏这种维生素的雄性中。严重的VA缺乏会损害β-胡萝卜素以及维生素D和E的生物利用度。