MicroRNAs and other non-coding RNAs in adipose tissue and obesity: emerging roles as biomarkers and therapeutic targets

Abstract

Obesity is a metabolic condition usually accompanied by insulin resistance (IR), type 2 diabetes (T2D), and dyslipidaemia, which is characterised by excessive fat accumulation and related to white adipose tissue (WAT) dysfunction. Enlargement of WAT is associated with a transcriptional alteration of coding and non-coding RNAs (ncRNAs). For many years, big efforts have focused on understanding protein-coding RNAs and their involvement in the regulation of adipocyte physiology and subsequent role in obesity. However, diverse findings have suggested that a dysfunctional adipocyte phenotype in obesity might be also dependent on specific alterations in the expression pattern of ncRNAs, such as miRNAs. The aim of this review is to update current knowledge on the physiological roles of miRNAs and other ncRNAs in adipose tissue function and their potential impact on obesity. Therefore, we examined their regulatory role on specific WAT features: adipogenesis, adipokine secretion, inflammation, glucose metabolism, lipolysis, lipogenesis, hypoxia and WAT browning. MiRNAs can be released to body fluids and can be transported (free or inside microvesicles) to other organs, where they might trigger metabolic effects in distant tissues, thus opening new possibilities to a potential use of miRNAs as biomarkers for diagnosis, prognosis, and personalisation of obesity treatment. Understanding the role of miRNAs also opens the possibility of using these molecules on individualised dietary strategies for precision weight management. MiRNAs should be envisaged as a future therapeutic approach given that miRNA levels could be modulated by synthetic molecules (f.i. miRNA mimics and inhibitors) and/or specific nutrients or bioactive compounds.

Circulating adiposity‐related microRNAs as predictors of the response to a low‐fat diet in subjects with obesity

“…11,25 Some miRNAs have been implicated in the control of body weight, glucose homeostasis, insulin sensitivity and lipid metabolism, 31,32 suggesting that miRNAs could be used as therapeutic targets for the treatment of metabolic disorders, but also as predictive biomarkers. 11 Circulating miRNAs are protected from RNAses in the extracellular environment especially through association with microvesicles, exosomes or proteins, thus participating in cell-to-cell communication. 33,34 Moreover, circulating miRNAs levels usually reflect a systemic response to an external stimulus and their expression measurements may uncover non-invasive biomarkers for human diseases.…”

“…These molecules have well‐known roles in the regulation of several biological processes, including cellular differentiation, proliferation, metabolism, ageing and apoptosis . Additionally, it is estimated that the miRNAs regulate the expression of more than 60% of protein‐coding genes ; thus, changes in miRNAs expression have been associated with several diseases, such as metabolic disorders and obesity …”

“…9 Additionally, it is estimated that the miRNAs regulate the expression of more than 60% of protein-coding genes 8 ; thus, changes in miRNAs expression have been associated with several diseases, such as metabolic disorders and obesity. 10,11 While some miRNAs are highly expressed in various tissues throughout the body, a subgroup of miRNAs are found circulating in biological fluids. 12 Some of them may be transported in an active form to other tissues, increasing the possibility of miRNA involvement in a cell-to-cell communication mode.…”

Harnessing adipogenesis to prevent obesity

“…In fact, an increasing number of genetic and epigenetic studies focusing on obesity revealed miRNAs as potent regulators of posttranscriptional expression of specific genes that are critical in the process of adipogenesis. In this regard, lists of miRNAs that enhance or inhibit adipocyte differentiation in murine preadipocytes or human APCs are reported in recent reviews [32][33][34]. Briefly, several miRNAs (miR-21, miR-29b, miR-144-3p, miR-148a, miR-210, miR-205-5p) enhance adipogenesis by interfering with the expression of molecular components involved in pathways that counteract adipogenesis (TGF-β, TNF-α, Wnt, corepressors of C/EBPα) [35][36][37][38][39][40].…”

Precision Nutrition and Metabolic Syndrome Management

“…In that context, precision nutrition and medicine should consider updated individualized nutritional status indicators for metabolic care and clinical nutrition [6], not only in patients suffering chronic diseases [7] or systemic inflammatory disturbances [8], but also in healthy subjects [9]. Similarly, it is necessary to take into account the development of new transcriptomic biomarkers [10], lipidomic and metabolomic tools [11,12], pharmacogenetic approaches [13] and metagenomic applications [14]. Also, the origins and developmental issues concerning health and disease or epigenetics in line with the developmental origins of health and disease (DOHaD) theory [15] are of interest in precision nutrition [16,17], including specific aspects on obesity [18] and metabolic syndrome features related to liver disease [19].…”