Activation of PPAR gamma induces profound multilocularization of adipocytes in adult mouse white adipose tissues.
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.
Koh
Young Jun
YJ
National 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.
Park
Byung-Hyun
BH
Park
Ji-Hyun
JH
Han
Jinah
J
Lee
In-Kyu
IK
Park
Jin Woo
JW
Koh
Gou Young
GY
D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D052436:Adipose Tissue, White / Q000166:cytology*; D058667:Adrenergic beta-3 Receptor Agonists; D000818:Animals; D002352:Carrier Proteins; D048750:Cell Nucleus Division; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007473:Ion Channels / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D047493:PPAR alpha / Q000819:agonists / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism*; D000070778:Perilipin-1; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010750:Phosphoproteins / Q000378:metabolism; D000077205:Pioglitazone; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors; D000071256:Uncoupling Protein 1
D058667:Adrenergic beta-3 Receptor Agonists; D002352:Carrier Proteins; D007004:Hypoglycemic Agents; D007473:Ion Channels; D024101:Mitochondrial Proteins; D047493:PPAR alpha; D047495:PPAR gamma; D000070778:Perilipin-1; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010750:Phosphoproteins; C485290:Ppargc1a protein, mouse; D045162:Thiazolidinediones; D015534:Trans-Activators; D014157:Transcription Factors; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D000077154:Rosiglitazone; D000077205:Pioglitazone