microRNAs in the Regulation of Adipogenesis and Obesity

Abstract

Worldwide obesity is a growing health problem, associated with increased risk of chronic disease. Understanding the molecular basis of adipogenesis and fat cell development in obesity is essential to identify new biomarkers and therapeutic targets for the development of anti-obesity drugs. microRNAs (miRNAs) appear to play regulatory roles in many biological processes associated with obesity, including adipocyte differentiation, insulin action and fat metabolism. Recent studies show miRNAs are dysregulated in obese adipose tissue. During adipogenesis miRNAs can accelerate or inhibit adipocyte differentiation and hence regulate fat cell development. In addition miRNAs may regulate adipogenic lineage commitment in multipotent stem cells and hence govern fat cell numbers. Recent findings suggest miR-519d may be associated with human obesity, but larger case-control studies are needed. Few miRNA targets have been experimentally validated in adipocytes but interestingly both miR-27 and miR-519d target PPAR family members, which are well established regulators of fat cell development. In this review recent advances in our understanding of the role of miRNAs in fat cell development and obesity are discussed. The potential of miRNA based therapeutics targeting obesity is highlighted as well as recommendations for future research which could lead to a breakthrough in the treatment of obesity.

Nϵ‐Carboxymethyllysine Increases the Expression of miR‐103/143 and Enhances Lipid Accumulation in 3T3‐L1 Cells

“…MicroRNAs are small non‐coding RNAs for which regulatory functions on mRNAs involved in adipogenesis have been proposed [McGregor and Choi, 2011; Peng et al, 2014]. In the present study, customized miRNA microarrays comprising probes for all mature murine miRNA sequences available in the Sanger miRNA database (Release 19) were used for identifying miRNAs influenced by treatment with 500 μM CML starting at differentiation.…”

“…Since, microRNAs have been linked to the regulation of adipogenesis [McGregor and Choi, 2011], we performed measurements on the miRNA profile of 3T3‐L1 preadipocytes using custom miRNA microarrays and digital droplet PCR. Furthermore, we determined whether CML exerts influence on fully differentiated adipocytes, which may aid in the development of adipocyte hypertrophy or modify adipocyte properties, in terms of gene expression, free fatty acid, and glucose uptake.…”

Obesity and p16INK4A Downregulation Activate Breast Adipocytes and Promote Their Protumorigenicity

“…Intriguingly, Obadi cells express almost undetectable levels of miR-141 and miR-146b-5p, indicating that the level of these two tumor suppressor microRNAs is also affected by obesity in BSAd. miRNA profiling studies have identified several miRNAs which are differentially expressed in adipogenesis and associated with obesity in various adipose depots (46,47). Furthermore, miR-141 was found downregulated in visceral adipose tissue of obese females (48), and miR-146b-5p was downregulated in monocytes during obesity (49).…”

Is Use of Micro-RNA–Containing Food Feasible?

“…The high-tech level functional food can be achieved by combining several core mi-RNAs mimics or antisense oligonucleotides that can selectively suppress target gene expression under physiologic conditions. Core miRNAs involved in various processes such as physical exercise [86,87], cough prevention or release [88], obesity [89,90], and cancer prevention [8] would be effective resource for food or animal feed. We can apply not only mimics of the core miRNAs as tumor suppress gene but also ASO of core miRNAs as oncogene with combination strategy.…”