Exp Mol Med.  2009 Dec;41(12):880-895. 10.3858/emm.2009.41.12.094.

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

Affiliations
  • 1National Research Laboratory of Vascular Biology and Graduate School of Medical Science and Engineering, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea. gykoh@kaist.ac.kr
  • 2Department of Biochemistry and Internal Medicine, College of Medicine, Chonbuk National University, Jeonju 560-180, Korea.
  • 3Department of Internal Medicine, Endocrinology Section, Kyungbook National University, Daegu 540-749, Korea.

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 beta3-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.

Keyword

mitochondria; mitochondrial uncoupling protein; pioglitazone; receptors, adrenergic, beta-3; rosiglitazone

MeSH Terms

Adipocytes/*cytology/metabolism
Adipose Tissue, White/*cytology
Animals
Cell Nucleus Division
Hypoglycemic Agents/pharmacology
Ion Channels/metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Obese
Mitochondria/metabolism
Mitochondrial Proteins/metabolism
PPAR alpha/agonists/metabolism
PPAR gamma/*agonists/*metabolism
Phosphoproteins/metabolism
Receptors, Adrenergic, beta-3/agonists
Thiazolidinediones/pharmacology
Trans-Activators/metabolism
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