Activation of PPARγ induces profound multilocularization of adipocytes in adult mouse white adipose tissues

Young Jun Koh,Gou Young Koh,Jinah Han,Jin Woo Park,In-Kyu Lee,Ji-Hyun Park,Byung-Hyun Park

doi:10.3858/emm.2009.41.12.094

Young Jun Koh, Gou Young Koh + Show 5 more

Open Access

https://doi.org/10.3858/emm.2009.41.12.094

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Abstract

We sought to determine the effects of activation of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) on multilocularization of adipocytes in adult white adipose tissue (WAT). Male C57BL/6 normal, db/db, and ob/ob mice were treated with agonists of PPAR-gamma, PPAR-alpha, or beta(3)-adrenoceptor for 3 weeks. To distinguish multilocular adipocytes from unilocular adipocytes, whole- mounted adipose tissues were co-immunostained for perilipin and collagen IV. PPAR-gamma activation with rosiglitazone or pioglitazone induced a profound change of unilocular adipocytes into smaller, multilocular adipocytes in adult WAT in a time-dependent, dose-dependent, and reversible manner. PPAR-alpha activation with fenofibrate did not affect the number of locules or remodeling. db/db and ob/ob obese mice exhibited less multilocularization in response to PPAR-gamma activation compared to normal mice. Nevertheless, all adipocytes activated by PPAR-gamma contained a single nucleus regardless of locule number. Multilocular adipocytes induced by PPAR-gamma activation contained substantially increased mitochondrial content and enhanced expression of uncoupling protein-1, PPAR-gamma coactivator-1-alpha, and perilipin. Taken together, PPAR-gamma activation induces profound multilocularization and enhanced mitochondrial biogenesis in the adipocytes of adult WAT. These changes may affect the overall function of WAT.

Highlights

PPARγ agonists are commonly used as insulin sensitizers for treating patients with type II diabetes (Fonseca, 2003; Hammarstedt et al, 2005)
In normal adult mice fed with normal diet (Control), most of the adipocytes in adult white adipose tissue (WAT) were round-shaped unilocular adipocytes and a few are multilocular adipocytes in subcutaneous (6.7%, n = 3,000 cells), epididymal (4.9%, n = 3,000 cells), and retroperitoneal (12.7%, n = 3,000 cells) adipose tissues (Figure 1)
Similar to the rosiglitazone treatment, at 3 weeks after the start of pioglitazone treatment, percentages of multilocular adipocytes in total adipocytes were markedly increased in subcutaneous (65.6%, n = 4,000 cells, P < 0.01), epididymal (54.6%, n = 4,000 cells, P < 0.01), and retroperitoneal (74.7%, n = 4,000 cells, P < 0.01) adipose tissues compared to the Control (Figures 1C and 1D)

Summary

Introduction

PPARγ agonists are commonly used as insulin sensitizers for treating patients with type II diabetes (Fonseca, 2003; Hammarstedt et al, 2005). Activation of PPARγ causes structural remodeling of adipocytes in adult WAT This remodeling is characterized by increased number of smaller adipocytes, reduced size of lipid droplet and enlarged rounded nuclei in adipocytes, and more matrix tissue surrounding the adipocytes, which have been visualized mainly by sectioned adipose tissues and conventional staining methods (Okuno et al, 1998; Toseland et al, 2001; Yamauchi et al, 2001). The origin of these smaller adipocytes is postulated to be the amplified differentiation of residential adipoblasts/preadipocytes or the active division of adipocytes themselves (Okuno et al, 1998; Yamauchi et al, 2001)

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