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早期断奶会导致成年大鼠脂肪库中特定的糖皮质激素信号传导。

Early weaning leads to specific glucocorticoid signalling in fat depots of adult rats.

作者信息

Miranda Rosiane Aparecida, Pietrobon Carla Bruna, Bertasso Iala Milene, Rodrigues Vanessa S Tavares, Lopes Bruna Pereira, Calvino Camila, de Oliveira Elaine, de Moura Egberto Gaspar, Lisboa Patrícia C

机构信息

Laboratory of Endocrine Physiology, Biology Institute, Rio de Janeiro State University, Rio de Janeiro, RJ, Brazil.

出版信息

Endocrine. 2020 Jan;67(1):180-189. doi: 10.1007/s12020-019-02080-y. Epub 2019 Sep 7.

Abstract

PURPOSE

Early weaning (EW) is a stressful condition that programmes a child to be overweight in adult life. Fat mass depends on glucocorticoids (GC) to regulate adipogenesis and lipogenesis. We hypothesised that the increased adiposity in models of EW was due to a disturbed HPA axis and/or disrupted GC function.

METHODS

We used two experimental models, pharmacological early weaning (PEW, dams were bromocriptine-treated) and non-pharmacological early weaning (NPEW, dams' teats were wrapped with a bandage), which were initiated during the last 3 days of lactation. Offspring from both genders was analysed on postnatal day 180.

RESULTS

Offspring in both models were overweight with increased visceral fat mass, but plasma corticosterone was increased in both genders in the PEW group but not the NPEW group. NPEW males had increased GRα expression in visceral adipose tissue (VAT), and GRα expression decreased in PEW males in subcutaneous adipose tissue (SAT). Females in both EW groups had increased 11βHSD1 expression in SAT. PEW males had increased C/EBPβ expression in SAT. PEW females had lower PPARy and FAS expression in VAT than the NPEW females. We detected a sex dimorphism in VAT and SAT in the EW groups regarding 11βHSD1, GRα and C/EBPβ expression.

CONCLUSIONS

The accumulated adiposity induced by EW exhibited distinct mechanisms depending on gender, specific fat deposition and GC metabolism and action. The higher proportion of VAT/SAT in both sets of EW males may be related to the action of GC in these tissues, and the higher conversion of GC in SAT in females may explain the differences in the fat distribution.

摘要

目的

早期断奶(EW)是一种应激状态,会使儿童在成年后易于超重。脂肪量取决于糖皮质激素(GC)来调节脂肪生成和脂质生成。我们推测,EW模型中肥胖的增加是由于下丘脑-垂体-肾上腺(HPA)轴紊乱和/或GC功能破坏所致。

方法

我们使用了两种实验模型,即药物性早期断奶(PEW,给母鼠注射溴隐亭)和非药物性早期断奶(NPEW,用绷带包裹母鼠乳头),均在哺乳期的最后3天开始。对出生后第180天的雌雄后代进行分析。

结果

两种模型的后代均超重,内脏脂肪量增加,但PEW组雌雄两性的血浆皮质酮均升高,而NPEW组未升高。NPEW雄性大鼠内脏脂肪组织(VAT)中糖皮质激素受体α(GRα)表达增加,而PEW雄性大鼠皮下脂肪组织(SAT)中GRα表达降低。两组EW雌性大鼠SAT中11β-羟基类固醇脱氢酶1(11βHSD1)表达均增加。PEW雄性大鼠SAT中C/EBPβ表达增加。PEW雌性大鼠VAT中过氧化物酶体增殖物激活受体γ(PPARy)和脂肪酸合成酶(FAS)表达低于NPEW雌性大鼠。我们在EW组的VAT和SAT中检测到11βHSD1、GRα和C/EBPβ表达存在性别差异。

结论

EW诱导的脂肪堆积表现出取决于性别、特定脂肪沉积以及GC代谢和作用的不同机制。两组EW雄性大鼠中较高的VAT/SAT比例可能与GC在这些组织中的作用有关,而雌性大鼠SAT中GC的较高转化率可能解释了脂肪分布的差异。

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