Introduction The prevalence for childhood overweight and obesity increased steadily in the past decades. Childhood obesity was defined as a disease by the World Health Organization [25] and by the American Medical Association (2013) [7] and is listed in the International Statistical Classification of Diseases and Related Health Problems in (ICD). In 2016 over 340 million children and adolescents, aged 5–19 were overweight or obese and current estimates suggest approximately 38 million children under the age of 5 as overweight or obese [25]. Amongst genetic factors and environmental influences, a variety of perinatal risk factors individually or in combination contributes to the development of infant obesity. Especially maternal pre-pregnancy obesity, excessive gestational weight gain and gestational diabetes result in pathological pregnancy conditions. Insulin resistance (IR), elevated blood glucose levels and hormonal disturbance provoke the malprogramming of infant’s energy metabolism [11]. In 2016, Romere et al. discovered asprosin as a new adipokine exerting decisive metabolic functions. Asprosin is the C-terminal peptide of the extracellular matrix protein fibrillin-1 that is cleaved off by the propeptide convertase furin during the secretory pathway [17]. According to the current paradigm, asprosin is released from white adipose tissue (WAT) into the blood stream to target metabolically relevant organs. Following a circadian oscillation, asprosin triggers hepatic glucose release via the OLFR734 receptor [14, 19] and impairs insulin secretion from pancreatic beta-cells [13]. Furthermore, asprosin crosses the blood–brain barrier, activates hunger-stimulating AgRP (Agouti-related peptide) hypothalamic neurons thereby evoking appetite stimulation in mice [6]. Also, insulin sensitivity in muscle cells is impaired by asprosin via the PKCδ/ SERCA-2 pathway by increasing inflammation and ER stress [12]. Serum asprosin levels are elevated in obese humans and mice, and neutralisation of asprosin via antibody treatment reduces food intake and body weight as well as improves insulin sensitivity in mice [6]. Further studies revealed that asprosin levels were significantly higher in patients with impaired glucose regulation and correlated with a variety of clinical parameters of glucose and lipid metabolic disorders [24]. Furthermore, asprosin levels were significantly higher in women with type 2 diabetes mellitus (T2DM), and positively correlated with IR in women with polycystic ovary syndrome (PCOS) [1, 15]. These observations suggest asprosin as a potential biomarker of early diagnosis in metabolic-related diseases and a new therapeutic target not only for T2DM and other metabolic disorders but also for counteracting the perinatal programming of childhood obesity (overview see Fig. 1). Currently, only little data regarding asprosin levels in pregnant women or children are available. So far, two clinical studies addressed maternal and newborn asprosin levels [3, 26] whereas three studies examined serum asprosin in overweight and obese children [16, 21, 23]. Zhong et al. examined 80 pregnant, non-obese women; 40 with gestational diabetes mellitus (GDM), and 40 with normal glucose tolerance (NGT), aged 18–40. All participants were without pre-existing diabetes mellitus (DM), history of macrosomia, nor stillbirth, polycystic ovary syndrome, nor medications of corticosteroids or antipsychotics. The authors performed asprosin measurements at three different time points, 18–20 gestational weeks (gws), 24–28 gws, as well as before delivery. Neonate asprosin protein concentrations were determined in umbilical cord plasma by ELISA, and additional asprosin protein expression analysis via western blots and immunohistochemistry were performed in placenta. Asprosin levels were elevated in plasma of

中文翻译：

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妊娠期和儿童期的白脂素

引言 在过去的几十年中，儿童超重和肥胖的患病率稳步上升。儿童肥胖被世界卫生组织 [25] 和美国医学会 (2013) [7] 定义为一种疾病，并被列入国际疾病和相关健康问题统计分类 (ICD)。2016 年，超过 3.4 亿 5-19 岁的儿童和青少年超重或肥胖，目前的估计表明大约有 3800 万 5 岁以下儿童超重或肥胖 [25]。在遗传因素和环境影响中，各种围产期风险因素单独或组合导致婴儿肥胖。尤其是孕妇孕前肥胖，妊娠期体重过度增加和妊娠期糖尿病会导致病理性妊娠状况。胰岛素抵抗 (IR)、血糖水平升高和激素紊乱会引起婴儿能量代谢的程序错误 [11]。2016 年，Romere 等人。发现白脂素作为一种新的脂肪因子发挥决定性的代谢功能。Asprosin 是细胞外基质蛋白 fibrillin-1 的 C 端肽，在分泌途径中被前肽转化酶弗林蛋白酶切割 [17]。根据目前的范例，白脂素从白色脂肪组织 (WAT) 释放到血流中，以靶向代谢相关器官。在昼夜节律振荡后，白脂素通过 OLFR734 受体触发肝脏葡萄糖释放 [14, 19] 并损害胰腺 β 细胞的胰岛素分泌 [13]。此外，白脂素穿过血脑屏障，激活刺激饥饿的 AgRP（刺豚鼠相关肽）下丘脑神经元，从而在小鼠中引起食欲刺激 [6]。此外，白脂素通过 PKCδ/SERCA-2 通路增加炎症和内质网应激，损害肌肉细胞中的胰岛素敏感性 [12]。肥胖人和小鼠的血清白脂素水平升高，通过抗体治疗中和白脂素可减少食物摄入和体重，并提高小鼠的胰岛素敏感性 [6]。进一步的研究表明，在葡萄糖调节受损的患者中，白脂素水平显着升高，并且与葡萄糖和脂质代谢紊乱的各种临床参数相关 [24]。此外，患有 2 型糖尿病 (T2DM) 的女性的白脂素水平显着更高，且与多囊卵巢综合征 (PCOS) 女性的 IR 呈正相关 [1, 15]。这些观察结果表明，白脂素是代谢相关疾病早期诊断的潜在生物标志物，是一种新的治疗靶标，不仅可以用于治疗 T2DM 和其他代谢紊乱，还可以用于对抗围产期儿童肥胖症（概述见图 1）。目前，关于孕妇或儿童白脂素水平的数据很少。到目前为止，有两项临床研究针对母亲和新生儿的白脂素水平 [3, 26]，而三项研究则针对超重和肥胖儿童的血清白脂素 [16, 21, 23]。钟等人。检查了 80 名怀孕的非肥胖妇女；40 名患有妊娠糖尿病 (GDM)，40 名患有正常糖耐量 (NGT)，年龄在 18-40 岁之间。所有参与者都没有预先存在的糖尿病 (DM)、巨大儿病史、死胎、多囊卵巢综合征、皮质类固醇或抗精神病药物。作者在三个不同的时间点进行了白脂素测量，即 18-20 孕周 (gws)、24-28 gws 以及分娩前。通过ELISA测定脐带血浆中的新生儿白脂素蛋白浓度，并通过蛋白质印迹和免疫组织化学在胎盘中进行额外的白脂素蛋白表达分析。血浆中白脂素水平升高 以及交货前。通过ELISA测定脐带血浆中的新生儿白脂素蛋白浓度，并通过蛋白质印迹和免疫组织化学在胎盘中进行额外的白脂素蛋白表达分析。血浆中白脂素水平升高 以及交货前。通过ELISA测定脐带血浆中的新生儿白脂素蛋白浓度，并通过蛋白质印迹和免疫组织化学在胎盘中进行额外的白脂素蛋白表达分析。血浆中白脂素水平升高