Childhood Obesity-Related Mechanisms: MicroRNome and Transcriptome Changes in a Nested Case-Control Study

Abstract

Childhood obesity could contribute to adulthood obesity, leading to adverse health outcomes in adults. However, the mechanisms for how obesity is developed are still unclear. To determine the epigenome-wide and genome-wide expression changes related with childhood obesity, we compared microRNome and transcriptome levels as well as leptin protein levels in whole bloods of 12 obese and 24 normal children aged 6 years. miR-328-3p, miR-1301-3p, miR-4685-3p, and miR-6803-3p were negatively associated with all obesity indicators. The four miRNAs were also associated with 3948 mRNAs, and separate 475 mRNAs (185 among 3948 mRNAs) were associated with all obesity indicators. The 2533 mRNAs (64.2%) among the 3948 mRNAs and 286 mRNAs (60.2%) among the 475 mRNAs were confirmed as targets of the four miRNAs in public databases through miRWalk 2.0. Leptin protein was associated with miR-6803-3p negatively and all obesity indicators positively. Using DAVID bioinformatics resources 6.8, top three pathways for obesity-related gene set were metabolic pathways, pathways in cancer, and PI3K-Akt signaling pathway. The top three obesity-related disease classes were metabolic, cardiovascular, and chemdependency. Our results support that childhood obesity could be developed through miRNAs-related epigenetic mechanism and, further, these obesity-related epigenetic changes could control the pathways related with the development of various diseases.

Does Childhood Obesity Trigger Neuroinflammation?

“…Childhood obesity is increasing all over the world, and it has become a serious challenge for global public health [ 20 ]. It is known that during obesity, adipose tissue undergoes immune, metabolic and functional changes [ 4 ].…”

miRNA and leptin signaling in metabolic diseases and at extreme environments

“… 87 The microRNAs‐related epigenetic mechanism in childhood obesity‐based study on 24 normal and 12 obese children of 6 years depicted the strategies to control the development of various diseases and obesity‐related epigenetic changes that decoded to have negative association between four miRNAs (miR‐1301‐3p, miR‐328‐3p, miR‐4685‐3p, miR‐6803‐3p) and leptin levels. 67 Therefore, it is very necessary to understand the feeding behavior, corresponding regulatory mechanisms for obesity prevention and treatment strategies both at the individual and population level to develop efficient therapeutic strategies against the major health challenge as several advances and medical therapies are found to be unsuccessful. 87 , 88 …”