Rowett Institute, University of Aberdeen, Aberdeen, United Kingdom.
PLoS One. 2020 Feb 14;15(2):e0228732. doi: 10.1371/journal.pone.0228732. eCollection 2020.
Adipose tissue development begins in utero and is a key target of developmental programming. Here the influence of nutritionally-mediated prenatal growth-restriction on perirenal adipose tissue (PAT) gene expression and adipocyte phenotype in late fetal life was investigated in both sexes in an ovine model. Likewise circulating leptin concentrations and non-esterified fatty acid (NEFA) and glycerol responses to glucose challenge were determined in relation to offspring adiposity at key stages from birth to mid-adult life. In both studies' singleton-bearing adolescent sheep were fed control or high nutrient intakes to induce normal or growth-restricted pregnancies, respectively. Fetal growth-restriction at day 130 of gestation (32% lighter) was characterised by greater body-weight-specific PAT mass and higher PAT expression of peroxisome proliferator-activated receptor gamma (PPARɤ), glycerol-3-phosphate dehydrogenase, hormone sensitive lipase (HSL), insulin-like growth factor 1 receptor, and uncoupling protein 1. Independent of prenatal growth, females had a greater body-weight-specific PAT mass, more multilocular adipocytes, higher leptin and lower insulin-like growth factor 1 mRNA than males. Growth-restricted offspring of both sexes (42% lighter at birth) were characterised by higher plasma NEFA concentrations across the life-course (post-fasting and after glucose challenge at 7, 32, 60, 85 and 106 weeks of age) consistent with reduced adipose tissue insulin sensitivity. Circulating plasma leptin correlated with body fat percentage (females>males) and restricted compared with normal females had more body fat and increased abundance of PPARɤ, HSL, leptin and adiponectin mRNA in PAT at necropsy (109 weeks). Therefore, prenatal nutrient supply and sex both influence adipose tissue development with consequences for lipid metabolism and body composition persisting throughout the life-course.
脂肪组织的发育始于宫内，并成为发育编程的关键靶标。在这里，我们研究了在绵羊模型中，营养介导的产前生长受限对胎儿后期肾脏周围脂肪组织（PAT）基因表达和脂肪细胞表型的影响。同样，我们还研究了循环瘦素浓度以及游离脂肪酸（NEFA）和甘油对葡萄糖刺激的反应与出生到成年中期关键阶段后代肥胖的关系。在这两项研究中，怀有单胎的青少年绵羊分别接受对照或高营养摄入饮食，以诱导正常或生长受限的妊娠。妊娠 130 天（32%体重减轻）时的胎儿生长受限表现为体重特异性 PAT 质量更大，过氧化物酶体增殖物激活受体γ（PPARγ）、甘油-3-磷酸脱氢酶、激素敏感脂肪酶（HSL）、胰岛素样生长因子 1 受体和解偶联蛋白 1 的 PAT 表达更高。与产前生长无关，女性的体重特异性 PAT 质量更大，多房性脂肪细胞更多，瘦素更高，胰岛素样生长因子 1 mRNA 更低。无论产前生长情况如何，雄性和雌性的生长受限后代（出生时体重减轻 42%）在整个生命过程中（禁食后和在 7、32、60、85 和 106 周龄时进行葡萄糖刺激后）都表现出更高的血浆 NEFA 浓度，这与脂肪组织胰岛素敏感性降低一致。循环血浆瘦素与体脂肪百分比相关（女性>男性），与正常女性相比，受限女性体脂肪更多，且在尸检时 PAT 中的 PPARγ、HSL、瘦素和脂联素 mRNA 丰度增加（109 周）。因此，产前营养供应和性别都影响脂肪组织的发育，对脂质代谢和体成分的影响在整个生命过程中都持续存在。
