Wallace Jacqueline M, Milne John S, Aitken Raymond P, Adam Clare L
Rowett Institute of Nutrition and HealthUniversity of Aberdeen, Bucksburn, Aberdeen AB21 9SB, UK
Rowett Institute of Nutrition and HealthUniversity of Aberdeen, Bucksburn, Aberdeen AB21 9SB, UK.
J Mol Endocrinol. 2014 Aug;53(1):131-44. doi: 10.1530/JME-14-0123. Epub 2014 Jun 13.
Intrauterine growth restriction (IUGR) is a risk factor for obesity, particularly when offspring are born into an unrestricted nutritional environment. In this study, we investigated the impact of IUGR and gender on circulating lipids and on expression of adipogenic, lipogenic and adipokine genes in perirenal adipose tissue. Singleton lambs born to overnourished adolescent dams were normal birth weight (N) or IUGR (32% lower birth weight due to placental insufficiency). IUGR lambs exhibited increased fractional growth rates but remained smaller than N lambs at necropsy (d77). At 48 days, fasting plasma triglycerides, non-esterified fatty acids and glycerol were elevated predominantly in IUGR males. Body fat content was independent of prenatal growth but higher in females than in males. In perirenal fat, relative to male lambs, females had larger adipocytes; higher lipoprotein lipase, fatty acid synthase and leptin and lower IGF1, IGF2, IGF1R, IGF2R and hormone-sensitive lipase mRNA expression levels, and all were independent of prenatal growth category; peroxisome proliferator-activated receptor gamma and glycerol-3-phosphate dehydrogenase (G3PDH) mRNA expression were not affected by IUGR or gender. Adiposity indices were inversely related to G3PDH mRNA expression, and for the population as a whole the expression of IGF system genes in perirenal fat was negatively correlated with plasma leptin, fat mass and adipocyte size, and positively correlated with circulating IGF1 levels. Higher plasma lipid levels in IUGR males may predict later adverse metabolic health and obesity, but in early postnatal life gender has the dominant influence on adipose tissue gene expression, reflecting the already established sexual dimorphism in body composition.
宫内生长受限（IUGR）是肥胖的一个风险因素，尤其是当后代出生在营养不受限的环境中时。在本研究中，我们调查了IUGR和性别对循环脂质以及对肾周脂肪组织中脂肪生成、脂质生成和脂肪因子基因表达的影响。由营养过剩的青春期母羊所生的单胎羔羊出生体重正常（N）或为IUGR（由于胎盘功能不全，出生体重低32%）。IUGR羔羊表现出更高的生长分数率，但在尸检时（第77天）仍比N羔羊小。在48天时，空腹血浆甘油三酯、非酯化脂肪酸和甘油主要在IUGR雄性羔羊中升高。体脂含量与产前生长无关，但雌性高于雄性。在肾周脂肪中，相对于雄性羔羊，雌性具有更大的脂肪细胞；脂蛋白脂肪酶、脂肪酸合酶和瘦素水平更高，而胰岛素样生长因子1（IGF1）、胰岛素样生长因子2（IGF2）、IGF1受体、IGF2受体和激素敏感性脂肪酶的mRNA表达水平更低，且所有这些均与产前生长类别无关；过氧化物酶体增殖物激活受体γ和甘油-3-磷酸脱氢酶（G3PDH）的mRNA表达不受IUGR或性别的影响。肥胖指数与G3PDH的mRNA表达呈负相关，对于总体人群而言，肾周脂肪中IGF系统基因的表达与血浆瘦素、脂肪量和脂肪细胞大小呈负相关，与循环IGF1水平呈正相关。IUGR雄性羔羊中较高的血浆脂质水平可能预示着后期不良的代谢健康和肥胖，但在出生后早期，性别对脂肪组织基因表达具有主要影响，这反映了身体组成中已确立的性别差异。
