title: Critical role of the peroxisomal protein PEX16 in white adipocyte development and lipid homeostasis.
abstract: The importance of peroxisomes for adipocyte function is poorly understood. Herein, we provide insights into the critical role of peroxin 16 (PEX16)-mediated peroxisome biogenesis in adipocyte development and lipid metabolism. Pex16 is highly expressed in adipose tissues and upregulated during adipogenesis of murine and human cells. We demonstrate that Pex16 is a target gene of the adipogenesis "master-regulator" PPARγ. Stable silencing of Pex16 in 3T3-L1 cells strongly reduced the number of peroxisomes while mitochondrial number was unaffected. Concomitantly, peroxisomal fatty acid (FA) oxidation was reduced, thereby causing accumulation of long- and very long-chain (polyunsaturated) FAs and reduction of odd-chain FAs. Further, Pex16-silencing decreased cellular oxygen consumption and increased FA release. Additionally, silencing of Pex16 impaired adipocyte differentiation, lipogenic and adipogenic marker gene expression, and cellular triglyceride stores. Addition of PPARγ agonist rosiglitazone and peroxisome-related lipid species to Pex16-silenced 3T3-L1 cells rescued adipogenesis. These data provide evidence that PEX16 is required for peroxisome biogenesis and highlights the relevance of peroxisomes for adipogenesis and adipocyte lipid metabolism.
authors.affiliation: Institute of Biochemistry, Graz University of Technology, Austria.
authors.forename: Dina C
authors.initials: DC
authors.lastname: Hofer
authors.affiliation: Institute of Biochemistry, Graz University of Technology, Austria.
authors.forename: Ariane R
authors.initials: AR
authors.lastname: Pessentheiner
authors.affiliation: Institute of Biochemistry, Graz University of Technology, Austria.
authors.forename: Helmut J
authors.initials: HJ
authors.lastname: Pelzmann
authors.affiliation: Institute of Molecular Biology and Biochemistry, Medical University of Graz, Austria.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Schlager
authors.affiliation: Institute of Molecular Biology and Biochemistry, Medical University of Graz, Austria.
authors.forename: Corina T
authors.initials: CT
authors.lastname: Madreiter-Sokolowski
authors.affiliation: Institute of Cell Biology, Histology and Embryology/Center for Medical Research, Medical University of Graz, Austria.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Kolb
authors.affiliation: Institute of Molecular Biosciences, University of Graz, Austria.
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Eichmann
authors.affiliation: Institute of Molecular Biosciences, University of Graz, Austria; Omics-Center, BioTechMed, Graz, Austria.
authors.forename: Gerald
authors.initials: G
authors.lastname: Rechberger
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Bilban
authors.affiliation: Institute of Molecular Biology and Biochemistry, Medical University of Graz, Austria.
authors.forename: Wolfgang F
authors.initials: WF
authors.lastname: Graier
authors.affiliation: Institute of Molecular Biology and Biochemistry, Medical University of Graz, Austria.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Kratky
authors.affiliation: Institute of Biochemistry, Graz University of Technology, Austria. Electronic address: juliane.bogner-strauss@tugraz.at.
authors.forename: Juliane G
authors.initials: JG
authors.lastname: Bogner-Strauss
mesh_terms: D041721:3T3-L1 Cells; D052438:Adipocytes, White / Q000378:metabolism*; D050156:Adipogenesis / Q000502:physiology; D000818:Animals; D019556:COS Cells; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D002522:Chlorocebus aethiops; D005227:Fatty Acids / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology*; D008055:Lipids / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010101:Oxygen Consumption / Q000502:physiology; D047495:PPAR gamma / Q000378:metabolism; D020675:Peroxisomes / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D005227:Fatty Acids; D008055:Lipids; D008565:Membrane Proteins; D047495:PPAR gamma
keywords: Adipogenesis; Lipid homeostasis; PEX16; PPARγ; Peroxisome