Effect of Pioglitazone on the Fructose-Induced Abdominal Adipose Tissue Dysfunction

Ana Alzamendi,Eduardo Spinedi,Oscar R Rebolledo,Juan J Gagliardino,Andrés Giovambattista,María E García

doi:10.1155/2012/259093

Abstract

Aim. To test the potential role of PPARγ in the endocrine abdominal tissue dysfunction induced by feeding normal rats with a fructose rich diet (FRD) during three weeks. Methodology. Adult normal male rats received a standard commercial diet (CD) or FRD, (10% in drinking water) without or with pioglitazone (PIO) (i.p. 0.25 mg/Kg BW/day; CD-PIO and FRD-PIO). Thereafter, we measured circulating metabolic, endocrine, and oxidative stress (OS) markers, abdominal adipose tissue (AAT) mass, leptin (LEP) and plasminogen activator inhibitor-1 (PAI-1) tissue content/expression, and leptin release by isolated adipocytes incubated with different concentrations of insulin. Results. Plasma glucose, insulin, triglyceride, TBARS, LEP, and PAI-1 levels were higher in FRD rats; PIO coadministration fully prevented all these increments. AAT adipocytes from FRD rats were larger, secreted a higher amount of LEP, and displayed decreased sensitivity to insulin stimulation; these effects were significantly ameliorated by PIO. Whereas AAT LEP and PAI-1 (mRNA) concentrations increased significantly in FRD rats, those of insulin-receptor-substrate- (IRS-) 1 and IRS-2 were reduced. PIO coadministration prevented FRD effects on LEP, PAI-1, and IRS-2 (fully) and IRS-1 (partially) mRNAs in AAT. Conclusion. PPARγ would play a relevant role in the development of the FRD-induced metabolic-endocrine dysfunction.

Highlights

The annual per capita consumption of fructose has drastically risen in the USA in recent decades [1], and some authors consider that this increased consumption could actively contribute to the development of the current epidemics of obesity, type 2 diabetes, and metabolic syndrome (MS) [2, 3]
On account that PPAR-γ plays an important role in the control of tissue-insulin sensitivity, we currently studied the involvement of those receptors in the fructose rich diet (FRD)-induced abdominal adipose tissue (AAT) endocrine dysfunction
We investigated the effect of simultaneous administration of FRD and pioglitazone (PIO), an effective PPAR-γ agonist [26, 27] on (a) circulating concentrations of metabolic, endocrine, and oxidative stress (OS) markers, (b) morphometric characteristics of AAT adipocytes, (c) in vitro leptin release by isolated AAT adipocytes, and (d) expression of adipokines and of intracellular insulin mediators (insulin-receptor-substrate- (IRS-) 1 and IRS-2) in the AAT

Summary

Introduction

The annual per capita consumption of fructose has drastically risen in the USA in recent decades [1], and some authors consider that this increased consumption could actively contribute to the development of the current epidemics of obesity, type 2 diabetes, and metabolic syndrome (MS) [2, 3]. The precise mechanism whereby FRD induces the features of MS is still controversial, it has been suggested that an increased rate of oxidative stress (OS) is actively involved [9,10,11,12,13] In this regard, we have previously reported increased OS in abdominal adipose tissue (AAT) [14] and impaired adipoinsular axis function [14, 15] in normal rats fed an FRD for 3 weeks. The facts that the intake of an FRD increases serum triglyceride and insulin levels and impairs glucose tolerance supports this assumption [14, 15] All these alterations could be consequences of the enhancement in the OS rate [14] and/or the impairment of tissue insulin sensitivity induced by fructose [6, 23,24,25]

Methods

Results

Discussion

Conclusion