Abstract

Child and adolescent obesity constitute one of the greatest contemporary public health menaces. The enduring disproportion between calorie intake and energy consumption, determined by a complex interaction of genetic, epigenetic, and environmental factors, finally leads to the development of overweight and obesity. Child and adolescent overweight/obesity promotes smoldering systemic inflammation (“para-inflammation”) and increases the likelihood of later metabolic and cardiovascular complications, including metabolic syndrome and its components, which progressively deteriorate during adulthood. Exosomes are endosome-derived extracellular vesicles that are secreted by a variety of cells, are naturally taken-up by target cells, and may be involved in many physiological and pathological processes. Over the last decade, intensive research has been conducted regarding the special role of exosomes and the non-coding (nc) RNAs they contain (primarily micro (mi) RNAs, long (l) non-coding RNAs, messenger (m) RNAs and other molecules) in inter-cellular communications. Through their action as communication mediators, exosomes may contribute to the pathogenesis of obesity and associated disorders. There is increasing evidence that exosomal miRNAs and lncRNAs are involved in pivotal processes of adipocyte biology and that, possibly, play important roles in gene regulation linked to human obesity. This review aims to improve our understanding of the roles of exosomes and their cargo in the development of obesity and related metabolic and inflammatory disorders. We examined their potential roles in adipose tissue physiology and reviewed the scarce data regarding the altered patterns of circulating miRNAs and lncRNAs observed in obese children and adolescents, compared them to the equivalent, more abundant existing findings of adult studies, and speculated on their proposed mechanisms of action. Exosomal miRNAs and lncRNAs could be applied as cardiometabolic risk biomarkers, useful in the early diagnosis and prevention of obesity. Furthermore, the targeting of crucial circulating exosomal cargo to tissues involved in the pathogenesis and maintenance of obesity could provide a novel therapeutic approach to this devastating and management-resistant pandemic.

Highlights

  • As defined by the World Health Organization (WHO), overweight and obesity are characterized by potentially detrimental excessive fat accumulation

  • Considering that exosome-mediated intra-adipose and inter-organ communication appears to be of great significance for energy metabolism, there seems to be a special function of exosomes in adipose tissue biology, which may be disrupted in obesity

  • HLA complex P5 (HCP5) polymorphisms have been associated with autoimmune disorders, leading to the hypothesis that HCP5related disruption of immune response can contribute to childhood obesity; HCP5 functions as a competing endogenous RNA binding to miR17-5p and increasing Ras-related protein R-Ras (RRAS) protein expression in the mitogen-activated protein kinase (MAPK) signaling pathway, which regulates adipocyte carbohydrate metabolism, promoting childhood obesity development [106]

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Summary

Introduction

As defined by the World Health Organization (WHO), overweight and obesity are characterized by potentially detrimental excessive fat accumulation. Exosomal microRNAs (miRNAs) appear to be involved in obesity and its cardiometabolic sequelae by acting as signaling entities, mediating the crosstalk among adipose tissue, liver, skeletal muscles and immune cells, and promoting inflammation in these organs [8]. These biological properties of exosomes and the non-coding RNAs they contain suggest that they could hold great potential for the diagnosis and treatment of obesity and its detrimental complications. The most recent, complete and relevant reviews and original articles on the topic, published up to November 2020, were selected

Biogenesis and Secretion of Exosomes
Exosomal miRNAs and lncRNAs
Adipose Tissue Depots
Endocrine Properties of Adipose Tissue
Adipose-Derived Exosomes
Current Knowledge
Evolutionary and Genetic Basis of Obesity
Environmental and Epigenetic Contributing Factors
Clinical Use of Exosomes and Therapeutic Aspects
Findings
Conclusions and Future Perspectives
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