Early Life Nutrition Research Unit, Division of Human Development, Academic Child Health, School of Clinical Sciences, University Hospital, University of Nottingham, Nottingham NG7 2UH, UK.
J Endocrinol. 2010 Feb;204(2):173-9. doi: 10.1677/JOE-09-0358. Epub 2009 Nov 24.
Maternal parity influences size at birth, postnatal growth and body composition with firstborn infants being more likely to be smaller with increased fat mass, suggesting that adiposity is set in early life. The precise effect of parity on fat mass and its endocrine sensitivity remains unclear and was, therefore, investigated in the present study. We utilised an established sheep model in which perirenal-abdominal fat mass (the major fat depot in the neonatal sheep) increases approximately 10-fold over the first month of life and focussed on the impact of parity on glucocorticoid sensitivity and adipokine expression in the adipocyte. Twin-bearing sheep of similar body weight and adiposity that consumed identical diets were utilised, and maternal blood samples were taken at 130 days of gestation. One offspring from each twin pair was sampled at 1 day of age, coincident with the time of maximal recruitment of uncoupling protein 1 (UCP1), whilst its sibling was sampled at 1 month, when UCP1 had disappeared. Plasma leptin was lower in nulliparous mothers than in multiparous mothers, and offspring of nulliparous mothers possessed more adipose tissue with increased mRNA abundance of leptin, glucocorticoid receptor and UCP2, adaptations that persisted up to 1 month of age when gene expression for interleukin-6 and adiponectin was also raised. The increase in fat mass associated with firstborn status is therefore accompanied by a resetting of the leptin and glucocorticoid axis within the adipocyte. Our findings emphasise the importance of parity in determining adipose tissue development and that firstborn offspring have an increased capacity for adipogenesis which may be critical in determining later adiposity.
产妇生育次数会影响出生时的体重、出生后的生长和身体成分，头胎婴儿更有可能体重较小，体脂较多，这表明脂肪含量在生命早期就已经确定。生育次数对脂肪量及其内分泌敏感性的确切影响尚不清楚，因此本研究对此进行了调查。我们利用了一种已建立的绵羊模型，在该模型中，肾周-腹部脂肪量（新生绵羊的主要脂肪储存库）在生命的第一个月内增加了约 10 倍，我们专注于生育次数对脂肪细胞中糖皮质激素敏感性和脂肪因子表达的影响。我们使用了体重和肥胖程度相似的双胎母羊，并在妊娠 130 天时采集母羊血液样本。从每对双胞胎中各取一只羔羊，在 1 天大时进行采样，此时解偶联蛋白 1（UCP1）的最大募集时间，而其同胞在 1 个月大时进行采样，此时 UCP1 已经消失。初产母羊的血浆瘦素水平低于多产母羊，初产母羊的后代拥有更多的脂肪组织，瘦素、糖皮质激素受体和 UCP2 的 mRNA 丰度增加，这些适应一直持续到 1 个月大，此时白细胞介素-6 和脂联素的基因表达也增加。因此，与头胎出生相关的脂肪量增加伴随着脂肪细胞中瘦素和糖皮质激素轴的重置。我们的研究结果强调了生育次数在决定脂肪组织发育中的重要性，并且头胎后代具有增加的脂肪生成能力，这可能对确定后期肥胖至关重要。
