Abstract

BackgroundVisceral fat plays a central role in the development of metabolic syndrome and atherosclerotic cardiovascular diseases. The association of visceral fat accumulation with cardio-metabolic diseases has been reported, but the impact of visceral fat on the gene expression profile in peripheral blood cells remains to be determined. The aim of this study was to determine the effects of visceral fat area (VFA) and subcutaneous fat area (SFA) on the gene expression profile in peripheral blood cells of obese subjects.MethodsAll 17 enrolled subjects were hospitalized to receive diet therapy for obesity (defined as body mass index, BMI, greater than 25 kg/m2). VFA and SFA were measured at the umbilical level by computed tomography (CT). Blood samples were subjected to gene expression profile analysis by using SurePrint G3 Human GE Microarray 8 × 60 k ver. 2.0. The correlation between various clinical parameters, including VFA and SFA, and peripheral blood gene expression levels was analyzed.ResultsAmong the 17 subjects, 12 had normal glucose tolerance or borderline diabetes, and 5 were diagnosed with type 2 diabetes without medications [glycated hemoglobin (HbA1c); 6.3 ± 1.3%]. The mean BMI, VFA, and SFA were 30.0 ± 5.5 kg/m2, 177 ± 67 and 245 ± 131 cm2, respectively. Interestingly, VFA altered the expression of 1354 genes, including up-regulation of 307 and down-regulation of 1047, under the statistical environment that the parametric false discovery rate (FDR) was less than 0.1. However, no significant effects were noted for SFA or BMI. Gene ontology analysis showed higher prevalence of VFA-associated genes than that of SFA-associated genes, among the genes associated with inflammation, oxidative stress, immune response, lipid metabolism, and glucose metabolism.ConclusionsAccumulation of visceral fat, but not subcutaneous fat, has a significant impact on the gene expression profile in peripheral blood cells in obese Japanese subjects.

Highlights

  • Visceral fat plays a central role in the development of metabolic syndrome and atherosclerotic car‐ diovascular diseases

  • The aim of the present study was to define the association of visceral fat area (VFA) and subcutaneous fat area (SFA) determined by computed tomography (CT), with the gene expression profile in peripheral blood cells in obese subjects free of overt diabetes

  • The target probes were selected under the condition that significant signals were detected in more than 7 cases among 17 subjects and 23,197 probes were extracted for gene expression analysis

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Summary

Introduction

Visceral fat plays a central role in the development of metabolic syndrome and atherosclerotic car‐ diovascular diseases. The association of visceral fat accumulation with cardio-metabolic diseases has been reported, but the impact of visceral fat on the gene expression profile in peripheral blood cells remains to be determined. We have examined the role of gene expression profile in peripheral blood cells, and reported that visceral adiposity can alter the expression profiles of various genes in peripheral blood cells, including those involved in circadian rhythm and inflammation [8, 9]. In these studies, visceral adiposity, including VFA and SFA, was not assessed by modern precision technology such as computed tomography (CT). Lee et al [10] found a significant association between VFA, but not SFA, and sirtuin 1 (SIRT1) mRNA level in peripheral blood mononuclear cells

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