Impact of age on cardiometabolic health in children at adiposity rebound: the role of genetic mechanisms

脂肪重积聚时相对儿童心血管代谢健康的影响：遗传的作用机制

Authors：Ling Luo, Fang-Biao Tao

Source：World Journal of Pediatrics

DOI: 10.1007/s12519-025-00893-8

Abstract

Background: Identifying effective predictors early in life is crucial to enable timely prevention and intervention to improve cardiometabolic health outcomes. Adiposity rebound (AR) is an important period in early life, with earlier AR increasing the risk of cardiometabolic abnormalities. However, the role and mechanism of genetic factors in this association are unclear. Therefore, this study reviews the potential genetic mechanisms influencing the age at AR, as well as the genetic mechanisms linking earlier AR with cardiometabolic abnormalities.

Data sources: A comprehensive literature search was conducted in PubMed and China National Knowledge Infrastructure databases using a combination of medical subject headings terms and related keywords, including "adiposity rebound", "cardiometabolic", "obesity", "BMI trajectory", "diabetes mellitus", "dyslipidemias", "hypertension", "metabolic syndrome", "genetics", and "epigenetic". Citation tracking was performed as a supplementary search strategy. All potentially relevant articles were subsequently subjected to full-text evaluation for eligibility assessment.

Results: Polymorphisms in the DMRT1, FTO, LEPR, and TFAP2B genes, along with obesity susceptibility, can influence the age at AR. Single-nucleotide polymorphisms associated with the age at AR are enriched in the insulin-like growth factor 1 (IGF-1) signaling pathway, which can be modulated by the LEPR and TFAP2B genes. Shared genetic mechanisms between cardiometabolic abnormalities and the age at AR are influenced by obesity-related genetic variants. These variants regulate the growth hormone (GH)/IGF-1 axis, advancing AR and leading to cardiometabolic abnormalities. Earlier AR alters adiponectin and leptin levels, further activating the GH/IGF-1 axis and creating a vicious cycle. Long-term breastfeeding can counteract the adverse effects of obesity-related genetic susceptibility on AR timing, thereby reducing the genetic risk of cardiometabolic abnormalities.

Conclusions: Our results support earlier AR as a marker for identifying cardiometabolic risk and screening high-risk populations at the genetic level.

Keywords: Adiposity rebound; Cardiometabolic abnormalities; Epigenetics; Genetics.

摘要

背景：在生命早期探索有效的预测因子从而实现及时地预防和干预是改善心血管代谢异常的关键所在。脂肪重积聚（AR）是生命早期的重要时期之一。AR时相提前将会增加心血管代谢异常的风险。但是，遗传因素在该关联中发挥的作用和机制尚不明确。因此，本研究综述了影响AR时相的潜在遗传机制以及AR时相与心血管代谢异常关联的遗传机制。

数据来源：利用主题词与副主题词或相近词相结合的形式，在Pubmed和中国知网上对“脂肪重积聚”“心血管代谢”“肥胖”“BMI轨迹”“糖尿病”“血脂异常”“高血压”“代谢综合征”“遗传学”“表观遗传学”等单个或组合的关键词进行全面检索，并进行引文检索作为补充，最后对潜在相关文献进行全文评估。

结果：DMRT1、FTO、LEPR和TFAP2B基因多态性和肥胖易感性能够影响AR时相。与AR时相相关的单核苷酸多态性富集于胰岛素样生长因子1（IGF-1）信号通路，该信号通路受到LEPR和TFAP2B基因调节。心血管代谢异常与AR时相具有共同的遗传机制，均受到肥胖相关遗传变异的影响。而肥胖相关的遗传变异能够调节GH/IGF-1轴促使AR时相提前，进而导致心血管代谢异常。此外，AR时相提前能够改变脂联素和瘦素水平，进一步激活GH/IGF-1轴，继而形成恶性循环。通过长期母乳喂养可以抵消肥胖遗传易感性导致AR时相提前带来的危害，从而降低心血管代谢异常的遗传风险。

结论：在遗传层面为AR时相提前作为早期识别心血管代谢健康风险和筛查高危人群的标志物提供了支持。