FABP4 dynamics in obesity: discrepancies in adipose tissue and liver expression regarding circulating plasma levels.

Joan Vendrell,María Isabel Queipo-Ortuño,Belen Peral,Merce Miranda,Lourdes Garrido-Sanchez,Fernando Cardona,Jose Manuel Fernández-Real,Victoria Ceperuelo-Mallafré,Xavier Escoté,Francisco J Tinahones,Mercedes Clemente-Postigo,Rafael Pérez-Pérez

doi:10.1371/journal.pone.0048605

Abstract

BackgroundFABP4 is predominantly expressed in adipose tissue, and its circulating levels are linked with obesity and a poor atherogenic profile.ObjectiveIn patients with a wide BMI range, we analyze FABP4 expression in adipose and hepatic tissues in the settings of obesity and insulin resistance. Associations between FABP4 expression in adipose tissue and the FABP4 plasma level as well as the main adipogenic and lipolytic genes expressed in adipose tissue were also analyzed.MethodsThe expression of several lipogenic, lipolytic, PPAR family and FABP family genes was analyzed by real time PCR. FABP4 protein expression in total adipose tissues and its fractions were determined by western blot.ResultsIn obesity FABP4 expression was down-regulated (at both mRNA and protein levels), with its levels mainly predicted by ATGL and inversely by the HOMA-IR index. The BMI appeared as the only determinant of the FABP4 variation in both adipose tissue depots. FABP4 plasma levels showed a significant progressive increase according to BMI but no association was detected between FABP4 circulating levels and SAT or VAT FABP4 gene expression. The gene expression of FABP1, FABP4 and FABP5 in hepatic tissue was significantly higher in tissue from the obese IR patients compared to the non-IR group.ConclusionThe inverse pattern in FABP4 expression between adipose and hepatic tissue observed in morbid obese patients, regarding the IR context, suggests that both tissues may act in a balanced manner. These differences may help us to understand the discrepancies between circulating plasma levels and adipose tissue expression in obesity.

Highlights

Cytoplasmic fatty-acid-binding proteins (FABPs) are proteins with a tissue-specific distribution implicated in cellular uptake and transport of fatty acids as well as coordination of metabolic and inflammatory pathways and modulation of gene expression [1,2]
The inverse pattern in FABP4 expression between adipose and hepatic tissue observed in morbid obese patients, regarding the IR context, suggests that both tissues may act in a balanced manner
In others prospective studies FABP4 levels are considered an early marker of metabolic risk for metabolic syndrome development and T2D [4,17,18]. These findings suggest that circulating FABP4 could promote inflammation, mediate insulin resistance, type 2 diabetes and atherosclerosis

Summary

Introduction

Cytoplasmic fatty-acid-binding proteins (FABPs) are proteins with a tissue-specific distribution implicated in cellular uptake and transport of fatty acids as well as coordination of metabolic and inflammatory pathways and modulation of gene expression [1,2]. FABP4 is highly expressed in adipose tissue and expressed in macrophages; it is one of the most abundant proteins in mature adipocytes [3] and is detected at high concentrations in human serum [4,5]. FABP4 has emerged as an important mediator in the crosstalk between adipocytes and macrophages in adipose tissue. Animal studies have shown that FABP4 knock-out mice are protected from the development of obesity-induced IR, impaired glucose tolerance and atherosclerosis, and their adipocytes have reduced lipolysis effectiveness [7,8]. FABP4 is predominantly expressed in adipose tissue, and its circulating levels are linked with obesity and a poor atherogenic profile

Methods

Results

Conclusion