Abstract

Evidence suggests that visceral fat accumulation plays a central role in the development of metabolic syndrome. Excess visceral fat causes local chronic low-grade inflammation and dysregulation of adipocytokines, which contribute in the pathogenesis of the metabolic syndrome. These changes may affect the gene expression in peripheral blood cells. This study for the first time examined the association between visceral fat adiposity and gene expression profile in peripheral blood cells. The gene expression profile was analyzed in peripheral blood cells from 28 obese subjects by microarray analysis. Reverse transcription-polymerase chain reaction (RT-PCR) was performed using peripheral blood cells from 57 obese subjects. Obesity was defined as body mass index (BMI) greater than 25 kg/m2 according to the Japanese criteria, and the estimated visceral fat area (eVFA) was measured by abdominal bioelectrical impedance. Analysis of gene expression profile was carried out with Agilent whole human genome 4×44 K oligo-DNA microarray. The expression of several genes related to circadian rhythm, inflammation, and oxidative stress correlated significantly with visceral fat accumulation. Period homolog 1 (PER1) mRNA level in blood cells correlated negatively with visceral fat adiposity. Stepwise multiple regression analysis identified eVFA as a significant determinant of PER1 expression. In conclusion, visceral fat adiposity correlated with the expression of genes related to circadian rhythm and inflammation in peripheral blood cells.

Highlights

  • It has been shown that there is a significant association between computed tomography (CT)-based fat distribution and life stylerelated diseases, such as diabetes, dyslipidemia, and hypertension

  • The main findings of the present study were: (1) Visceral fat adiposity correlated with the expression of various genes related to circadian rhythm, inflammation, and oxidative stress, in peripheral blood cells

  • The present data are in agreement with the reported increase in monocytes in obese subjects [18]

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Summary

Introduction

It has been shown that there is a significant association between computed tomography (CT)-based fat distribution and life stylerelated diseases, such as diabetes, dyslipidemia, and hypertension. Visceral fat-related obesity is closely associated with the development of atherosclerotic diseases [1]. The exact pathomechanisms of the metabolic syndrome are not clear at present but seem to involve accumulation of macrophages in adipose tissue, which induce a state of chronic low-grade inflammation by producing a battery of inflammatory mediators. These macrophages interact with adipocytes through free fatty acids and adipocytokines, creating a vicious cycle that promotes the development of the metabolic syndrome and atherosclerosis [2,3,4]. To date, there is no method to evaluate the function and condition of human visceral fat

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