Wallace Jacqueline M, Milne John S, Aitken Raymond P, Redmer Dale A, Reynolds Lawrence P, Luther Justin S, Horgan Graham W, Adam Clare L
Rowett Institute of Nutrition and Health University of Aberdeen, Bucksburn, Aberdeen AB21 9SB, UK Department of Animal Sciences North Dakota State University, Fargo, North Dakota 58108-6050, USA Biomathematics and Statistics Scotland Aberdeen AB21 9SB, UK
Rowett Institute of Nutrition and Health University of Aberdeen, Bucksburn, Aberdeen AB21 9SB, UK Department of Animal Sciences North Dakota State University, Fargo, North Dakota 58108-6050, USA Biomathematics and Statistics Scotland Aberdeen AB21 9SB, UK.
J Mol Endocrinol. 2015 Jun;54(3):263-75. doi: 10.1530/JME-15-0048. Epub 2015 Apr 27.
Low birthweight is a risk factor for neonatal mortality and adverse metabolic health, both of which are associated with inadequate prenatal adipose tissue development. In the present study, we investigated the impact of maternal undernutrition on the expression of genes that regulate fetal perirenal adipose tissue (PAT) development and function at gestation days 89 and 130 (term=145 days). Singleton fetuses were taken from adolescent ewes that were either fed control (C) intake to maintain adiposity throughout pregnancy or were undernourished (UN) to maintain conception weight but deplete maternal reserves (n=7/group). Fetal weight was independent of maternal intake at day 89, but by day 130, fetuses from UN dams were 17% lighter and had lower PAT mass that contained fewer unilocular adipocytes. Relative PAT expression of IGF1, IGF2, IGF2R and peroxisome proliferator-activated receptor gamma (PPARG) mRNA was lower in UN than in controls, predominantly at day 89. Independent of maternal nutrition, PAT gene expression of PPARG, glycerol-3-phosphate dehydrogenase, hormone sensitive lipase, leptin, uncoupling protein 1 and prolactin receptor increased, whereas IGF1, IGF2, IGF1R and IGF2R decreased between days 89 and 130. Fatty acid synthase and lipoprotein lipase (LPL) mRNAs were not influenced by nutrition or stage of pregnancy. Females had greater LPL and leptin mRNA than males, and LPL, leptin and PPARG mRNAs were decreased in UN at day 89 in females only. PAT gene expression correlations with PAT mass were stronger at day 89 than they were at day 130. These data suggest that the key genes that regulate adipose tissue development and function are active beginning in mid-gestation, at which point they are sensitive to maternal undernutrition: this leads to reduced fetal adiposity by late pregnancy.
低出生体重是新生儿死亡和不良代谢健康的一个风险因素，这两者均与产前脂肪组织发育不足有关。在本研究中，我们调查了母体营养不足对妊娠第89天和130天（足月为145天）调节胎儿肾周脂肪组织（PAT）发育和功能的基因表达的影响。单胎胎儿取自青春期母羊，这些母羊要么在整个孕期给予对照（C）摄入量以维持肥胖，要么营养不足（UN）以维持受孕体重但消耗母体储备（每组n = 7）。在第89天，胎儿体重与母体摄入量无关，但到第130天，来自营养不足母羊的胎儿体重轻17%，PAT质量较低，其中单泡脂肪细胞较少。UN组中IGF1、IGF2、IGF2R和过氧化物酶体增殖物激活受体γ（PPARG）mRNA的相对PAT表达低于对照组，主要在第89天。与母体营养无关，PPARG、甘油-3-磷酸脱氢酶、激素敏感性脂肪酶、瘦素、解偶联蛋白1和催乳素受体的PAT基因表达在第89天至第130天之间增加，而IGF1、IGF2、IGF1R和IGF2R则减少。脂肪酸合酶和脂蛋白脂肪酶（LPL）mRNA不受营养或妊娠阶段的影响。雌性的LPL和瘦素mRNA高于雄性，仅在第89天雌性的UN组中LPL、瘦素和PPARG mRNA降低。PAT基因表达与PAT质量的相关性在第89天比在第130天更强。这些数据表明，调节脂肪组织发育和功能的关键基因在妊娠中期开始活跃，此时它们对母体营养不足敏感：这导致妊娠晚期胎儿肥胖减少。
