Narasimhan Kothandaraman, Tint Mya Thway, Chen Li, Mir Sartaj Ahmad, Sadananthan Suresh Anand, Michael Navin, Ramasamy Adaikalavan, Tan Karen Mei-Ling, Mishra Priti, Bendt Anne K, Tan Kok Hian, Cameron-Smith David, Chong Yap Seng, Gluckman Peter D, Meikle Peter J, Leow Melvin Khee Shing, Yap Fabian, Lee Yung Seng, Yng Chan Shiao, Eriksson Johan G, Velan S Sendhil, Karnani Neerja, Wenk Markus R
Institute for Human Development and Potential (IHDP), Agency for Science, Technology and Research (A*STAR), Brenner Centre for Molecular Medicine , 30 Medical Drive, Singapore, 117609, Singapore.
Life Sciences Institute, Singapore Lipidomics Incubator, National University of Singapore, Singapore, Singapore.
BMC Med. 2025 Apr 14;23(1):215. doi: 10.1186/s12916-025-04030-0.
Although the associations between cord blood lipidome and neonatal birth weight are established, it remains uncertain whether sexual dimorphism in fetal fat accumulation extends to the relationship between cord blood lipid profiles and neonatal abdominal fat compartments. Understanding these relationships could provide insights into early sex-specific differences in lipid metabolism.
We conducted lipidomics of umbilical cord blood plasma samples (350 (46.6%) girls and 401 (53.4%) boys) from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort. Abdominal fat compartments-superficial subcutaneous adipose tissue (sSAT), deep SAT (dSAT), and intra-abdominal adipose tissue (IAT)-were quantified by magnetic resonance imaging within 2 weeks of birth in 239 subjects. Linear regression models were used to assess sex differences in lipid species associated with abdominal fat compartments.
Newborn girls had significantly higher superficial and deep subcutaneous adipose tissue volumes compared to boys, whereas intra-abdominal adipose tissue volumes were similar between sexes. In the pooled analysis, cord blood plasma lipids showed distinct associations with different fat depots: 38 lipid species were associated with sSAT, 4 with dSAT, and 38 with IAT. In sex-stratified analyses, 13 lipids were associated with sSAT in girls and 3 in boys, whereas dSAT showed associations with 45 lipids in boys but none in girls. These sex differences were primarily observed in ether-linked phospholipids and ceramides. Notably, no significant associations were observed between lipids and IAT in either sex, suggesting depot-specific sexual dimorphism in early life.
Our study reveals sexual dimorphism in the associations between cord blood lipidome and abdominal adiposity, suggesting depot-specific patterns in adipose tissue development and lipid metabolism in early life.
尽管脐带血脂质组与新生儿出生体重之间的关联已得到证实，但胎儿脂肪堆积中的性别差异是否延伸至脐带血脂谱与新生儿腹部脂肪区室之间的关系仍不确定。了解这些关系有助于深入了解脂质代谢中早期的性别特异性差异。
我们对来自新加坡成长至健康结局（GUSTO）出生队列的脐带血血浆样本（350名（46.6%）女孩和401名（53.4%）男孩）进行了脂质组学分析。在239名受试者出生后2周内，通过磁共振成像对腹部脂肪区室——浅表皮下脂肪组织（sSAT）、深部皮下脂肪组织（dSAT）和腹内脂肪组织（IAT）进行了定量。使用线性回归模型评估与腹部脂肪区室相关的脂质种类的性别差异。
与男孩相比，新生女孩的浅表和深部皮下脂肪组织体积显著更高，而腹内脂肪组织体积在两性之间相似。在汇总分析中，脐带血血浆脂质与不同的脂肪储存部位显示出不同的关联：38种脂质与sSAT相关，4种与dSAT相关，38种与IAT相关。在按性别分层的分析中，13种脂质与女孩的sSAT相关，3种与男孩的sSAT相关，而dSAT与男孩的45种脂质相关，与女孩的脂质无相关性。这些性别差异主要在醚键连接的磷脂和神经酰胺中观察到。值得注意的是，在两性中均未观察到脂质与IAT之间的显著关联，这表明生命早期存在特定储存部位的性别差异。
我们的研究揭示了脐带血脂质组与腹部肥胖之间关联的性别差异，表明生命早期脂肪组织发育和脂质代谢中存在特定储存部位的模式。
