title: Mitochondrial biogenesis and remodeling during adipogenesis and in response to the insulin sensitizer rosiglitazone.
abstract: White adipose tissue is an important endocrine organ involved in the control of whole-body metabolism, insulin sensitivity, and food intake. To better understand these functions, 3T3-L1 cell differentiation was studied by using combined proteomic and genomic strategies. The proteomics approach developed here exploits velocity gradient centrifugation as an alternative to isoelectric focusing for protein separation in the first dimension. A 20- to 30-fold increase in the concentration of numerous mitochondrial proteins was observed during adipogenesis, as determined by mass spectrometry and database correlation analysis. Light and electron microscopy confirmed a large increase in the number of mitochondrion profiles with differentiation. Furthermore, mRNA profiles obtained by using Affymetrix GeneChips revealed statistically significant increases in the expression of many nucleus-encoded mitochondrial genes during adipogenesis. Qualitative changes in mitochondrial composition also occur during adipose differentiation, as exemplified by increases in expression of proteins involved in fatty acid metabolism and of mitochondrial chaperones. Furthermore, the insulin sensitizer rosiglitazone caused striking changes in mitochondrial shape and expression of selective mitochondrial proteins. Thus, although mitochondrial biogenesis has classically been associated with brown adipocyte differentiation and thermogenesis, our results reveal that mitochondrial biogenesis and remodeling are inherent to adipose differentiation per se and are influenced by the actions of insulin sensitizers.
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01615, USA.
authors.forename: Leanne
authors.initials: L
authors.lastname: Wilson-Fritch
authors.forename: Alison
authors.initials: A
authors.lastname: Burkart
authors.forename: Gregory
authors.initials: G
authors.lastname: Bell
authors.forename: Karen
authors.initials: K
authors.lastname: Mendelson
authors.forename: John
authors.initials: J
authors.lastname: Leszyk
authors.forename: Sarah
authors.initials: S
authors.lastname: Nicoloro
authors.forename: Michael
authors.initials: M
authors.lastname: Czech
authors.forename: Silvia
authors.initials: S
authors.lastname: Corvera
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D008854:Microscopy, Electron; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000077154:Rosiglitazone; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones
chemical_list: D007328:Insulin; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D013844:Thiazoles; D045162:Thiazolidinediones; D000077154:Rosiglitazone