Depot- and sex-specific effects of maternal obesity in offspring's adipose tissue
Depot- and sex-specific effects of maternal obesity in offspring's adipose tissue
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DOI：
10.1530/joe-16-0037
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发表时间：
2016-07-01
影响因子：
4
通讯作者：
Breton, Christophe
中科院分区：
文献类型：
--
作者：
Lecoutre, Simon;Deracinois, Barbara;Breton, Christophe
根据健康与疾病的发育起源（DOHaD）概念，胎儿或新生儿营养供应的改变会导致个体体重（BW）设定值的长期规划。特别是，母亲肥胖、营养过剩和新生儿生长加速已被证明会使后代对肥胖敏感。白色脂肪组织可能是由母体肥胖引起的代谢编程的主要目标。为了揭示潜在的机制，我们在妊娠和哺乳期前和期间建立了一个使用高脂肪（HF）饮食（含60%脂质）的母鼠肥胖模型。出生时，肥胖水坝（HF）的新生儿为正营养型。然而，HF新生儿在哺乳期间表现出快速的体重增加，这是啮齿动物脂肪组织发育的关键时期。在雄性中，断奶时体重增加（+30%）持续到3月龄。9个月大的HF雄性后代血糖正常，但表现为轻度葡萄糖耐受不良、高胰岛素血症和高皮质酮血症。尽管体重和能量摄入没有差异，但HF成年雄性后代更倾向于脂肪积累，表现为内脏（性腺和肾周）储存重量增加和高瘦素血症。然而，只有肾周脂肪组织库表现出明显的脂肪细胞肥大和增生，脂肪生成（如胆固醇调节元件结合蛋白1 （Srebp1）、脂肪酸合成酶（Fas）和瘦素）升高，脂肪生成(如过氧化物酶体增殖体激活受体γ （Ppar γ)、11 β -羟基类固醇脱氢酶1型（11 β - hds1）） mRNA水平降低。相比之下，在HF雌性后代中很少观察到代谢变化。因此，母亲的肥胖和哺乳期间的加速生长通过内脏脂肪组织的转录改变以一种储存和性别特异性的方式计划后代的高脂肪。
According to the Developmental Origin of Health and Disease (DOHaD) concept, alterations of nutrient supply in the fetus or neonate result in long-term programming of individual body weight (BW) setpoint. In particular, maternal obesity, excessive nutrition, and accelerated growth in neonates have been shown to sensitize offspring to obesity. The white adipose tissue may represent a prime target of metabolic programming induced by maternal obesity. In order to unravel the underlying mechanisms, we have developed a rat model of maternal obesity using a high-fat (HF) diet (containing 60% lipids) before and during gestation and lactation. At birth, newborns from obese dams (called HF) were normotrophs. However, HF neonates exhibited a rapid weight gain during lactation, a key period of adipose tissue development in rodents. In males, increased BW at weaning (+30%) persists until 3 months of age. Nine-month-old HF male offspring was normoglycemic but showed mild glucose intolerance, hyperinsulinemia, and hypercorticosteronemia. Despite no difference in BW and energy intake, HF adult male offspring was predisposed to fat accumulation showing increased visceral (gonadal and perirenal) depots weights and hyperleptinemia. However, only perirenal adipose tissue depot exhibited marked adipocyte hypertrophy and hyperplasia with elevated lipogenic (i.e. sterol-regulated element binding protein 1 (Srebp1), fatty acid synthase (Fas), and leptin) and diminished adipogenic (i.e. peroxisome proliferator-activated receptor gamma (Ppar gamma), 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-Hds1)) mRNA levels. By contrast, very few metabolic variations were observed in HF female offspring. Thus, maternal obesity and accelerated growth during lactation program offspring for higher adiposity via transcriptional alterations of visceral adipose tissue in a depot-and sex-specific manner.