Differential circulating and visceral fat microRNA expression of non-obese and obese subjects

doi:10.1016/j.clnu.2019.03.033

Clinical Nutrition

Volume 39, Issue 3, March 2020, Pages 910-916

https://doi.org/10.1016/j.clnu.2019.03.033 Get rights and content

Summary

Background & aims

Altered microRNA (miRNA) expression is associated with the pathophysiology of obesity; however, little is known about the miRNAs commonly dysregulated in the blood and visceral fat tissue of obese patients. This study compared the circulating and visceral fat miRNA expression in subjects with and without obesity.

Methods

For the circulating miRNA study, 20 healthy control and 30 obese subjects were recruited. For the tissue miRNA expression study, omental fat tissue was collected in ten female subjects each in the control and obese groups. MiRNA expression was measured by TaqMan low-density arrays. Metabolic risk factors were measured. Target genes for selected miRNAs were analyzed using informatics tools and a functional network map was constructed.

Results

11 miRNAs were down-regulated (miR-133a, -139-5p, -15b, -26a, -301, -30b, -30c, -374, -451, -570, and -636), and one was up-regulated (miR-155) in both depots in obese subjects. These miRNAs had significant associations with BMI, waist circumference, and fat mass. Among them, miR-15b, miR-26a, miR-301, miR-30b, and miR-30c had more predicted obesity-related target genes than other miRNAs. In particular, miR-15b had numerous target genes associated with adipogenesis, mammalian target of rapamycin (mTOR) signaling, diabetes and insulin resistance, and mitochondrial function.

Conclusions

It is suggested that the miRNA alteration in the serum and visceral fat has pathophysiological implications for obesity. Our study identified dysregulated miRNAs that may be novel therapeutic targets to combat obesity.

Introduction

MicroRNAs (miRNAs) are a class of endogenous, small (21–23 nucleotides in length), non-coding but functional RNAs. Mature miRNAs are generated from sequential processing of the primary miRNA transcript and then serve as posttranscriptional regulators of gene expression through complementary base pairing to messenger RNAs [1]. Since being discovered, miRNAs have been proven to play roles in diverse diseases, including cancer, inflammatory diseases, diabetes, and obesity [2], [3], [4].

There are several experimental studies demonstrating that obesity changes the miRNA expression in metabolically important organs, and conversely, miRNAs are involved in the pathophysiology of obesity, insulin resistance, and diabetes [3], [5]. The miR-17/92, miR-143/145, miR-130, let-7, miR-221/222, miR-200, miR-223, miR-29, and miR-375 families are reportedly associated with insulin signaling, immune-mediated inflammation, adipokine expression, adipogenesis, lipid metabolism, and food intake regulation [2].

Ortega et al. identified 11 miRNAs significantly dysregulated in the subcutaneous fat of obese subjects [6]. Subsequently, Heneghan et al. demonstrated that miR-17-5-p and miR-132 were altered in the adipose tissue and circulation of obese individuals, highlighting their potential as novel biomarkers for obesity [7]. Several studies have described altered miRNA expression in the serum of obese individuals [8], [9], [10], [11], [12], in which multiple miRNAs were differentially expressed in each study. This lack of overlapping results may be due to the different participant recruitment, profiling platforms, and population diversity across the studies.

A few studies have compared miRNA profiles in subcutaneous and visceral fat depots, suggesting some similarities and differences [7], [13]. These miRNA expression differences may contribute to intrinsic differences between visceral and subcutaneous adipose tissue. In addition, human adipose tissue miRNA expression is correlated with the adipocyte phenotype, parameters of obesity, and glucose metabolism [13]. Therefore, identifying miRNAs that are dysregulated in both visceral fat and in the circulation could generate a useful biomarker for obesity. Nonetheless, few studies have compared the miRNA profiles in both the serum and adipose tissue of obese patients after excluding the impact of diabetes. Profiling in obese Asians, in particular, has been understudied.

Therefore, the aim of the present study was to compare the miRNA profiles of both visceral adipose tissue and serum from subjects with and without obesity and to investigate whether miRNA expression was associated with the metabolic parameters. Our goal was to provide information about obesity-specific miRNA profiling in Koreans.

Section snippets

Subjects

The present study was composed of two subsets. For the circulating miRNA study, subjects aged 30–70 years were recruited on a voluntary basis among those who underwent routine health check-ups at the Center for Health Promotion at Korea University Ansan Hospital. Those with a medical history of diabetes, hypertension, or cardiovascular disease (CVD) were excluded. Those who were taking estrogen, oral contraceptives, or medications affecting inflammation (i.e., nonsteroidal anti-inflammatory

Subject characteristics

The baseline characteristics of the study participants are presented in Table 1. The mean BMI of the control and obese groups was 22.1 ± 1.7 and 29.5 ± 2.2 kg/m², respectively. Therefore, metabolic parameters, such as blood glucose, blood pressure, lipid profile, and fat percentage were higher in the obese group than control subjects. The mean age in the fat tissue study was 43.0 ± 5.6 versus 43.0 ± 4.9 years old, and the mean BMI was 21.7 ± 2.1 versus 30.5 ± 2.9 kg/m² in the control and obese

Discussion

In the present study, we found that the majority of differentially expressed miRNAs in the circulation and visceral fat tissue were primarily down-regulated in subjects with obesity relative to non-obese controls. The expression patterns were quite different between these two depots, leaving only 12 miRNAs as commonly dysregulated in obese subjects. These miRNAs had significant associations with obesity measures and glucose levels, and appeared to represent a close network with many target

Conclusion

In conclusion, we identified a set of miRNAs that are dysregulated in both the circulation and visceral fat tissue in obese Korean subjects. Considering the function of the targets of these miRNAs, their alteration is likely to play some role in the pathophysiology of obesity. Alteration of circulating miRNAs may constitute a novel biomarker for risk estimation and classification of obese patients. Because of the cross-over expression of miRNAs between normal and obese groups, the reliability

Author contributions

N.H.K. conceived and designed the study and wrote the first draft of the manuscript. H.J.C., J.H.Y., and J.A.S. helped with the data analysis. Y.M.C., H.J.S., and W.H.C collected and analyzed the data and coordinated the study. Y.J.J, J.A., and C.H.J. helped to design the study and assisted with data interpretation. T.Y.H. conceived the idea, its experimental design, and supervised the study and is the guarantor of this work and, as such, has full access to all the data in the study.

Conflict of interest

No potential conflicts of interest relevant to this article were reported.

Acknowledgements

This study was supported by grants from the Korea Food Research Institute and the Korean government (MSIP, NRF-2015R1A2A2A01003167).

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¹: These two authors contributed equally to this work.

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Original articleDifferential circulating and visceral fat microRNA expression of non-obese and obese subjects

Summary

Background & aims

Methods

Results

Conclusions

Introduction

Section snippets

Subjects

Subject characteristics

Discussion

Conclusion

Author contributions

Conflict of interest

Acknowledgements

Trends Cell Biol

Gene

Obes Res Clin Pract

J Biol Chem

Curr Biol CB

MicroRNAs as regulators of metabolic disease: pathophysiologic significance and emerging role as biomarkers and therapeutics

Int J Obes

MicroRNA regulatory networks in human adipose tissue and obesity

Nat Rev Endocrinol

MicroRNAs: critical mediators of differentiation, development and disease

Swiss Med Wkly

A plasma microRNA panel for early detection of colorectal cancer

Int J Cancer

MiRNA expression profile of human subcutaneous adipose and during adipocyte differentiation

PLoS One

Differential miRNA expression in omental adipose tissue and in the circulation of obese patients identifies novel metabolic biomarkers

J Clin Endocrinol Metab

Circulating miR-130b mediates metabolic crosstalk between fat and muscle in overweight/obesity

Diabetologia

Targeting the circulating microRNA signature of obesity

Clin Chem

Changes in circulating microRNAs are associated with childhood obesity

J Clin Endocrinol Metab

MicroRNA expression in human omental and subcutaneous adipose tissue

PLoS One

Follow-up report on the diagnosis of diabetes mellitus

Diabetes Care

MicroRNA and 3T3-L1 pre-adipocyte differentiation

Rna

Original article
Differential circulating and visceral fat microRNA expression of non-obese and obese subjects