Abstract
Obesity is a multifactorial and complex condition that is characterized by abnormal and excessive white adipose tissue accumulation, which can lead to the development of metabolic diseases, such as type 2 diabetes mellitus, nonalcoholic fatty liver disease, cardiovascular diseases, and several types of cancer. Obesity is characterized by excessive adipose tissue accumulation and associated with alterations in immunity, displaying a chronic low-grade inflammation profile. Adipose tissue is a dynamic and complex endocrine organ composed not only by adipocytes, but several immunological cells, which can secrete hormones, cytokines and many other factors capable of regulating metabolic homeostasis and several critical biological pathways. Remarkably, adipose tissue is a major source of circulating microRNAs (miRNAs), recently described as a novel form of adipokines. Several adipose tissue–derived miRNAs are deeply associated with adipocytes differentiation and have been identified with an essential role in obesity-associated inflammation, insulin resistance, and tumor microenvironment. During obesity, adipose tissue can completely change the profile of the secreted miRNAs, influencing circulating miRNAs and impacting the development of different pathological conditions, such as obesity, metabolic syndrome, and cancer. In this review, we discuss how miRNAs can act as epigenetic regulators affecting adipogenesis, adipocyte differentiation, lipid metabolism, browning of the white adipose tissue, glucose homeostasis, and insulin resistance, impacting deeply obesity and metabolic diseases. Moreover, we characterize how miRNAs can often act as oncogenic and tumor suppressor molecules, significantly modulating cancer establishment and progression. Furthermore, we highlight in this manuscript how adipose tissue–derived miRNAs can function as important new therapeutic targets.
Highlights
The worldwide statistics of overweight and obesity are considered a threat and contribute to a set of risk factors that enhances the development of several other diseases, such as type 2 diabetes, cardiovascular diseases, and cancer [1]
Several works have shown the role of miRNAs in the development of metabolic disease, glucose homeostasis, and progression of obesity [44,45,46,47]. miRNAs can exhibit a crucial impact on adipose tissues (Table 1) and influence the phenotype and function of white miRNAs in Obesity and Cancer and brown adipocyte [75]. miRNAs can function both as activators and inhibitors of brown adipogenesis and are crucial for adipose tissue plasticity and dynamics of adipocytes differentiation [76, 77]
Obesity can often lead to metabolic impairment, triggering inflammation, and contributing to disorders related to adipogenesis and lipid metabolism
Summary
The worldwide statistics of overweight and obesity are considered a threat and contribute to a set of risk factors that enhances the development of several other diseases, such as type 2 diabetes, cardiovascular diseases, and cancer [1]. The adipose tissue increases in mass and quantity, with a significant change in its metabolic and immunological profile, followed by adipocyte lytic cell death This adipocyte death triggers free fatty acids and several metabolites release, pivoting the immune repertoire toward a type 1 (proinflammatory) state and establishing a microenvironment that supports oxidative stress, free radicals generation associated with DNA damage and mutations. Several inflammatory genes upregulation in immune cells can drive the inflammatory response itself in adipose tissue, contributing to the insulin resistance and glucose intolerance [6], critical factors associated with metabolic syndrome Those metabolic and inflammatory changes in adipose tissue can disrupt physiological homeostasis both within local tissues and systemically, impacting directly the obesity development, as well as the initiation and progression of cancer and metabolic syndrome, creating positive feedback loops among them. Recent studies have highlighted the importance of adipose tissue resident macrophages as a principal source for this inflammatory signature supporting meta-inflammation and miRNAs are key molecules in these signaling pathways [11]
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