Pediatric Endocrinology Group, Girona Biomedical Research Institute, Girona, Spain.
Department of Biochemistry and Molecular Biomedicine, Universitat de Barcelona, Barcelona, Spain.
Pediatr Res. 2022 Jan;91(1):107-115. doi: 10.1038/s41390-021-01422-9. Epub 2021 Mar 2.
Accelerated catch-up growth following intrauterine restriction increases the risk of developing visceral adiposity and metabolic abnormalities. However, the underlying molecular mechanisms of such metabolic programming are still poorly understood.
A Wistar rat model of catch-up growth following intrauterine restriction was used. A gene expression array was performed in the retroperitoneal adipose tissue sampled at postnatal day (PD) 42.
Five hundred and forty-six differentially expressed genes (DEGs) were identified (adjusted p value < 0.05). Gene ontology enrichment analysis identified pathways related to immune and lipid metabolic processes, brown fat cell differentiation, and regulation of PI3K. Ccl21, Npr3, Serpina3n, Pnpla3, Slc2a4, and Serpina12 were validated to be upregulated in catch-up pups (all p < 0.01) and related to several fat expansion and metabolic parameters, including body weight at PD42, postnatal body weight gain, white and brown adipose tissue mass, plasma triglycerides, and insulin resistance index (all p < 0.05).
Genes related to immune and metabolic processes were upregulated in retroperitoneal adipose tissue following catch-up growth in juvenile rats and were found to be associated with fat expansion and metabolic parameters. Our results provide evidence for several dysregulated genes in white adipose tissue that could help develop novel strategies to prevent the metabolic abnormalities associated with catch-up growth.
Catch-up growth presents several dysregulated genes in white adipose tissue related to metabolic abnormalities. Ccl21, Npr3, Serpina3n, Pnpla3, Slc2a4, and Serpina12 were validated to be upregulated in catch-up pups and related to visceral fat expansion and metabolic parameters. Profiling and validation of these dysregulated genes in visceral adipose tissue could help develop novel strategies to prevent the metabolic abnormalities associated with catch-up growth.
宫内限制后加速追赶生长会增加发生内脏肥胖和代谢异常的风险。然而，这种代谢编程的潜在分子机制仍知之甚少。
我们使用了宫内限制后追赶生长的 Wistar 大鼠模型。在产后第 42 天采集的腹膜后脂肪组织中进行基因表达谱分析。
鉴定出 546 个差异表达基因（DEGs）（调整后的 p 值<0.05）。基因本体富集分析确定了与免疫和脂质代谢过程、棕色脂肪细胞分化以及 PI3K 调节相关的途径。Ccl21、Npr3、Serpina3n、Pnpla3、Slc2a4 和 Serpina12 在追赶生长的幼崽中被验证上调（均 p<0.01），并与几个脂肪扩张和代谢参数相关，包括 PD42 时的体重、出生后体重增加、白色和棕色脂肪组织质量、血浆甘油三酯和胰岛素抵抗指数（均 p<0.05）。
在幼鼠追赶生长后的腹膜后脂肪组织中，与免疫和代谢过程相关的基因上调，并与脂肪扩张和代谢参数相关。我们的研究结果为白色脂肪组织中几个失调的基因提供了证据，这些基因可能有助于开发预防与追赶生长相关的代谢异常的新策略。
追赶生长表现出与代谢异常相关的几个白色脂肪组织失调基因。Ccl21、Npr3、Serpina3n、Pnpla3、Slc2a4 和 Serpina12 在追赶生长的幼崽中被验证上调，并与内脏脂肪扩张和代谢参数相关。对这些内脏脂肪组织中失调基因的分析和验证，可能有助于开发预防与追赶生长相关的代谢异常的新策略。
