35 Changes in epigenetic regulation are associated with metabolic disease and inflammation in pediatric obesity

Background

Chronic low-grade inflammation plays a pivotal role in dysregulation of central pathways involved in lipid and glucose metabolism in obesity leading to metabolic disease. MicroRNAs (miRNAs) are known to fine-tune gene expression upstream from known regulators of metabolic homeostasis. We aimed to assess the relationship of circulating miRNAs with inflammatory modulators and metabolic disorders in pediatric obesity.

Methods

From a pediatric cohort with severe obesity (n=109), clinically thoroughly characterized including diverse routine blood parameters, oral glucose tolerance test and liver MRI, a panel of 16 circulating miRNAs was quantified using qRT-PCR. Additionally, markers of inflammation TNFα, IL1 receptor antagonist, procalcitonin, CRP and IL-6 were measured.

Results

We identified a strong yet unrecognized relationship of miRNAs 34a, 122 and 192 with both obesity-associated inflammation and metabolic disease. Concentrations of miRNAs 122 and 192 correlated with serum adiponectin that links adipose tissue inflammation to glucose metabolism. Several miRNA levels including miRNAs 34a, 93, 122, and 192 were statistically significantly differing between individuals with prediabetes, impaired glucose tolerance, metabolic syndrome, or non-alcoholic fatty liver disease compared and the respective controls. Additionally, miRNA 192 was significantly elevated in metabolically unhealthy obesity.

Conclusions

An unfavorable miRNA pattern related to obesity-associated inflammation and comorbidities is already present in children and may be used to distinguish metabolically healthy from unhealthy pediatric patients with obesity. Moreover, these changes in epigenetic regulation could potentially be involved in the etiology of obesity-linked metabolic disease in children and adolescents.

Publication History

Article published online:
24 September 2021