DuPriest E A, Kupfer P, Lin B, Sekiguchi K, Morgan T K, Saunders K E, Chatkupt T T, Denisenko O N, Purnell J Q, Bagby S P
1Department of Medicine, Oregon Health & Science University, Portland, OR, USA.
5Department of Pathology, Oregon Health & Science University, Portland, OR, USA.
J Dev Orig Health Dis. 2012 Jun;3(3):198-209. doi: 10.1017/S2040174412000232.
Adipose tissue (AT) dysfunction links obesity of any cause with cardiometabolic disease, but whether early-life nutritional deficiency can program adipocyte dysfunction independently of obesity is untested. In 3-5-month-old juvenile microswine offspring exposed to isocaloric perinatal maternal protein restriction (MPR) and exhibiting accelerated prepubertal fat accrual without obesity, we assessed markers of acquired obesity: adiponectin and tumor necrosis factor (TNF)-α messenger ribonucleic acid (mRNA) levels and adipocyte size in intra-abdominal (ABD-AT) and subcutaneous (SC-AT) adipose tissues. Plasma cortisol, leptin and insulin levels were measured in fetal, neonatal and juvenile offspring. In juvenile low-protein offspring (LPO), adipocyte size in ABD-AT was reduced 22% (P = 0.011 v. controls), whereas adipocyte size in SC-AT was increased in female LPO (P = 0.05) and normal in male LPO; yet, adiponectin mRNA in LPO was low in both sexes and in both depots (P < 0.001). Plasma leptin (P = 0.004) and cortisol (P < 0.05) were reduced only in neonatal LPO during MPR. In juveniles, correlations between % body fat and adiponectin mRNA, TNF-α mRNA or plasma leptin were significant in normal-protein offspring (NPO) but absent in LPO. Plasma glucose in juvenile LPO was increased in males but decreased in females (interaction, P = 0.023); plasma insulin levels and insulin sensitivity were unaffected. Findings support nutritional programming of adipocyte size and gene expression and subtly altered glucose homeostasis. Reduced adiponectin mRNA and adipokine dysregulation in juvenile LPO following accelerated growth occurred independently of obesity, adipocyte hypertrophy or inflammatory markers; thus, perinatal MPR and/or growth acceleration can alter adipocyte structure and disturb adipokine homeostasis in metabolically adverse patterns predictive of enhanced disease risk.
脂肪组织（AT）功能障碍将任何原因引起的肥胖与心脏代谢疾病联系起来，但早期营养缺乏是否能独立于肥胖而导致脂肪细胞功能异常尚未得到验证。在3至5个月大的幼年微型猪后代中，这些后代在围产期经历了等热量的母体蛋白质限制（MPR），且在青春期前脂肪堆积加速但未出现肥胖，我们评估了后天性肥胖的标志物：脂联素和肿瘤坏死因子（TNF）-α信使核糖核酸（mRNA）水平以及腹内（ABD-AT）和皮下（SC-AT）脂肪组织中的脂肪细胞大小。在胎儿、新生儿和幼年后代中测量了血浆皮质醇、瘦素和胰岛素水平。在幼年低蛋白后代（LPO）中，ABD-AT中的脂肪细胞大小减少了22%（与对照组相比，P = 0.011），而SC-AT中的脂肪细胞大小在雌性LPO中增加（P = 0.05），在雄性LPO中正常；然而，LPO中两性和两个脂肪库中的脂联素mRNA均较低（P < 0.001）。仅在MPR期间的新生儿LPO中，血浆瘦素（P = 0.004）和皮质醇（P < 0.05）降低。在幼年时，正常蛋白后代（NPO）中体脂百分比与脂联素mRNA、TNF-α mRNA或血浆瘦素之间存在显著相关性，而LPO中不存在这种相关性。幼年LPO中的血浆葡萄糖在雄性中升高而在雌性中降低（交互作用，P = 0.023）；血浆胰岛素水平和胰岛素敏感性未受影响。研究结果支持脂肪细胞大小和基因表达的营养编程以及葡萄糖稳态的细微改变。在加速生长后的幼年LPO中，脂联素mRNA降低和脂肪因子失调独立于肥胖、脂肪细胞肥大或炎症标志物而发生；因此，围产期MPR和/或生长加速可改变脂肪细胞结构并扰乱脂肪因子稳态，呈现出预测疾病风险增加的代谢不良模式。
