MiRNAs have been identified as important regulators of adipose tissue development and function ^[1][11]. Adipose tissue is a crucial energy-storing organ and plays a significant role in metabolic homeostasis. MiRNAs control adipogenesis, the process by which pre-adipocytes differentiate into mature adipocytes, and also influence adipocyte metabolism, insulin sensitivity, and lipid storage ^[1][11]. The dysregulation of miRNAs in adipose tissue has been associated with obesity and related metabolic disorders. Understanding the specific miRNA-mediated regulatory mechanisms in adipose tissue development can provide valuable insights into the pathogenesis of obesity and potentially open up new avenues for therapeutic interventions targeting miRNAs to modulate adipose tissue function and combat metabolic diseases.

MiRNAs play a significant role in maintaining the balance between energy intake, storage, and expenditure in various tissues and organs.

MiRNAs have been implicated in the regulation of adipocyte differentiation and lipid metabolism. For example, miR-27a and miR-143 have been shown to promote adipogenesis in rat ^[2][12] and pig ^[3][13] by targeting key genes involved in adipocyte differentiation, such as PPARγ and adiponectin. On the other hand, miR-26a and miR-30d have been found to inhibit adipogenesis by suppressing the expression of adipogenic transcription factors ^[4][14].

Furthermore, miRNAs have been identified as regulators of brown adipose tissue (BAT) and its thermogenic function. MiR-133 and miR-455 have been shown to inhibit BAT development and thermogenesis by targeting key genes involved in brown adipocyte differentiation and function ^[5][15]. Conversely, miR-193b and miR-365 have been found to promote BAT activity and thermogenesis ^[5][15]. A recent multiomics study identified the key nodes likely controlling non-shivering thermogenesis in adipose tissue, and identified numerous miRNAs such as miRNA-27, miRNA-34a, miRNA-106b, and miRNA-125-5p ^[6][16].

In addition to adipose tissue, miRNAs also play a role in the regulation of hepatic lipid metabolism. MiR-122, for instance, is highly expressed in the liver and has been shown to regulate cholesterol and fatty acid metabolism ^[7][17]. Its inhibition leads to decreased hepatic lipid accumulation and improved insulin sensitivity. Non-alcoholic fatty liver disease (NAFLD) impacts the metabolic syndrome associated with obesity. A group investigated the pathophysiological role of miR-194 in metabolic dysfunction brought on by obesity and found that the consumption of a high-fat diet or exposure to palmitic acid significantly elevates the levels of miR-194 in the liver, both in living organisms and in cell cultures ^[8][18]. Inhibiting miR-194 expression shielded cultured liver cells from the inflammatory response induced by palmitic acid. miR-194 directly bound to the 3′-UTR of Farnesoid X Receptor (FXR), leading to the suppression of FXR/Nr1h4 gene expression. Conversely, silencing FXR eliminates the hepatic benefits observed in obese mice treated with a miR-194 inhibitor. These findings suggest that miR-194 and FXR could serve as potential diagnostic markers and therapeutic targets for NAFLD.

Moreover, miRNAs have been implicated in the regulation of glucose metabolism and insulin signaling. For example, miR-143 have been shown to regulate insulin sensitivity by targeting key components of glycolysis and insulin signaling pathways ^[9][19].

Overall, miRNAs play a crucial role in the regulation of energy homeostasis and metabolic pathways. The dysregulation of miRNA expression and function has been associated with metabolic disorders such as obesity, type 2 diabetes (T2D), and dyslipidemia. Therefore, understanding the intricate miRNA-mediated regulatory networks in energy metabolism holds promise for the development of novel therapeutic approaches for metabolic diseases.

MicroRNAs (miRNAs) play a crucial role in the regulation of inflammation and insulin resistance, two interconnected processes that contribute to the development of various metabolic disorders, including obesity, T2D, and cardiovascular diseases (CVD).

Inflammation is a fundamental response of the immune system to injury or infection. However, chronic low-grade inflammation mediated by the NLRP3 inflammasome can occur in adipose tissue and other metabolic organs in the context of obesity and insulin resistance ^[10][20]. MiRNAs are involved in the regulation of pro-inflammatory and anti-inflammatory pathways. For instance, miR-146a and miR-155 are key modulators of inflammation and play important roles in regulating immune responses ^[11][21]. The dysregulation of these miRNAs can contribute to sustained inflammation and impair insulin signaling.

Insulin resistance, a hallmark of T2D, occurs when cells become less responsive to the effects of insulin. MiRNAs are implicated in the regulation of insulin sensitivity by targeting key components of the insulin signaling pathway. For example, miR-29, miR-143, and miR-33 have been shown to modulate insulin sensitivity by regulating insulin receptor substrate-1 (IRS-1), a critical mediator of insulin signaling ^[12][22].

Furthermore, miRNAs are involved in the cross-talk between inflammation and insulin resistance. They can regulate the production of inflammatory cytokines and chemokines, as well as the expression of insulin signaling molecules. MiR-155, for instance, has been shown to promote both inflammation and insulin resistance by targeting multiple molecules involved in these processes ^[13][23]. More precisely, mice that display double knock-out for both ApoE and miR-155 have high-fat diet-induced obesity, adipocyte hypertrophy, non-alcoholic fatty liver disease, and increased plasma leptin ^[13][23].

2. MicroRNAs as Biomarkers for Obesity-Related Diseases

In chronic kidney disease (CKD), the altered expression of miRNAs has been observed in renal tissues but also in biofluids, such as urine and blood. These miRNAs modulate key molecular pathways involved in CKD pathogenesis, including transforming growth factor-beta (TGF-β) signaling, epithelial-to-mesenchymal transition (EMT), and fibrosis. For example, miR-21 is upregulated in CKD and promotes renal fibrosis by targeting anti-fibrotic factors ^[14][25]. MicroRNAs (miRNAs) have gained significant attention as potential biomarkers for obesity-related diseases due to their stability, tissue specificity, and altered expression patterns in various physiological and pathological conditions ^[15][39]. The identification of reliable biomarkers is crucial for the early detection, accurate diagnosis, and monitoring of obesity-related diseases. MiRNAs are thus emerging as promising candidates for fulfilling this role. The dysregulation of miRNAs has been observed in various obesity-related diseases, suggesting their involvement in disease pathogenesis. These dysregulated miRNAs can be detected in various biological samples, such as blood, serum, plasma, urine, and adipose tissue, making them accessible for non-invasive testing and potential clinical applications ^[15][39]. In T2D, several miRNAs have shown altered expression levels in insulin-producing pancreatic beta cells, liver, skeletal muscle, and adipose tissue. MiR-126, miR-375, and miR-29 have been implicated in pancreatic beta cell function and insulin secretion ^[16][17][18][32,40,41]. In cardiovascular diseases, miRNAs such as miR-21, miR-126, and miR-155 have been associated with endothelial dysfunction, atherosclerosis, and cardiac remodeling ^[19][24]. In NAFLD, miR-122, miR-34a, and miR-34c are dysregulated and play a role in hepatic lipid metabolism and inflammation ^[7][17]. MiRNAs have been identified as potential biomarkers for obesity-related cardiac abnormalities. Circulating levels of specific miRNAs, such as miR-21, miR-208a, and miR-499 ^[20][10], have been found to be altered in obese individuals and correlated with the severity of cardiac dysfunction. These findings highlight the potential of miRNAs as non-invasive diagnostic tools for assessing cardiac remodeling and dysfunction in obesity. The potential utility of miRNAs as biomarkers lies in their ability to discriminate between different disease states and provide information about disease severity, progression, and responses to treatment. High-throughput technologies, such as microarray analysis and next-generation sequencing, have enabled the identification of panels of miRNAs that exhibit differential expression patterns in obesity-related diseases. These panels can serve as signatures for disease classification and prediction. Moreover, advances in quantitative polymerase chain reaction (qPCR) and sequencing technologies have facilitated the development of robust and sensitive methods for miRNA detection and quantification. For this, one would need to compare, for example, obesity patients afflicted with CKD to obesity patients with no renal disorder, and detect the most deregulated miRNAs. MiRNAs also offer the advantage of being able to provide information about the underlying molecular mechanisms of disease. Through their regulatory roles, miRNAs can modulate key pathways involved in disease pathogenesis, including inflammation, insulin signaling, lipid metabolism, and cell proliferation. By studying the functional implications of dysregulated miRNAs, researchers can gain insights into disease mechanisms and identify potential therapeutic targets. Despite the potential of miRNAs as biomarkers, there are challenges that need to be addressed ^[21][42]. The standardization of sample collection, processing, and analysis methods is essential to ensure the reproducibility and comparability of results. Furthermore, the identification of disease-specific miRNA signatures requires large-scale validation studies involving diverse populations ^[22][43]. Additionally, the development of miRNA-based diagnostic tests and their integration into clinical practice requires regulatory approval and validation in prospective clinical trials. In conclusion, miRNAs hold great promise as biomarkers for obesity-related diseases. Their altered expression patterns in various biological samples make them attractive candidates for non-invasive testing and monitoring. The ability of miRNAs to provide insights into disease mechanisms further enhances their potential as diagnostic and prognostic tools. Continued research and validation efforts are needed to fully exploit the clinical utility of miRNAs in the management of obesity-related diseases, with the ultimate goal of improving patient outcomes and personalized medicine.