Functional Significance and Predictive Value of MicroRNAs in Pediatric Obesity: Tiny Molecules with Huge Impact?

Abstract

Obesity is a major health concern. While some children develop comorbidities such as insulin resistance and low-grade systemic inflammation upon weight gain, others stay metabolically healthy. There is an urgent need for clinically relevant markers with prognostic value related to disease development and intervention success. MicroRNAs (miRNAs) are established biomarkers for several disease states. Herein, we give a brief overview of miRNA biogenesis and function and the potential role of circulating miRNA in the context of pediatric obesity.

Novel Insights in the Metabolic Syndrome in Childhood and Adolescence

“…This includes classical hormones (such as leptin), growth factors (e.g., insulin-like growth factor-1 and platelet-derived growth factor), inflammatory mediators, enzymes, and metabolites (such as fatty acids). Thus, white adipose tissue is in permanent crosstalk influencing other organ systems through the production of these adipocytokines [47]. Altered levels of adipocytokines have been demonstrated as a common feature not only in obesity, but also in NAFLD and MetS in children and adolescents [48, 49].…”

“…Both hyperplastic and hypertrophic growth of adipocytes can be observed with diameters exceeding the maximal diffusion rate of oxygen. It is supposed that local hypoxia, cell death, and macrophage infiltration occur consequently and lead to an altered adipokine secretion profile with an upregulation of inflammatory factors, which contribute to the chronic low-grade inflammation observed in obesity [47]. This low-grade inflammation might underlie, at least in part, the clustering of cardiovascular risk factors [53].…”

“…They have emerged as key regulators of metabolism [76]. MiRNA were established as biomarkers for several diseases and are commonly studied in the context of metabolic disease [47, 77, 78]. Recently, various miRNAs associated with obesity or its complications were identified; a few examples will be further discussed.…”

“…Recently, various miRNAs associated with obesity or its complications were identified; a few examples will be further discussed. Several miRNA species, like miR-130 or miR-27b, regulate adipogenic differentiation by targeting the expression of peroxisome proliferator-activated receptor gamma (PPARγ), the master regulator of adipogenesis [47]. Along the same line, miR-125b-5p, which is upregulated during human adipogenesis, downregulates the antiadipogenic matrix metalloproteinase 11 and directly inhibits adipogenesis itself [79].…”

“…Although there are still many challenges and drawbacks, miRNAs are an exciting, novel, rapidly developing, and promising research field. They have the potential for employment in the diagnosis, stratification, and therapeutics in the context of metabolic disease [47]. …”