title: Peroxisome deficient aP2-Pex5 knockout mice display impaired white adipocyte and muscle function concomitant with reduced adrenergic tone.
abstract: Peroxisomes are essential for intermediary lipid metabolism, but the role of these organelles has been primarily studied in the liver. We recently generated aP2-Pex5 conditional knockout mice that due to the nonselectivity of the aP2 promoter, not only had dysfunctional peroxisomes in the adipose tissue but also in the central and peripheral nervous system, besides some other tissues. Peroxisomes were however intact in the liver, heart, pancreas and muscle. Surprisingly, these mice not only showed dysfunctional white adipose tissue with increased fat mass and reduced lipolysis but also the skeletal muscle was affected including impaired shivering thermogenesis, reduced motor performance and increased insulin resistance. Non-shivering thermogenesis by brown adipose tissue was not altered. Strongly reduced levels of plasma adrenaline and to a lesser extent noradrenaline, impaired expression of catecholamine synthesizing enzymes in the adrenal medulla and reversal of all pathologies after administration of the β-agonist isoproterenol indicated that β-adrenergic signaling was reduced. Based on normal white adipose and muscle function in Nestin-Pex5 and Wnt-Pex5 knockout mice respectively, it is unlikely that peroxisome absence from the central and peripheral nervous system caused the phenotype. We conclude that peroxisomal metabolism is necessary to maintain the adrenergic tone in mice, which in turn determines metabolic homeostasis.
authors.affiliation: Laboratory of Cell Metabolism, Department of Pharmaceutical Sciences, KU Leuven, Leuven, Belgium.
authors.forename: Katrin
authors.initials: K
authors.lastname: Martens
authors.forename: Astrid
authors.initials: A
authors.lastname: Bottelbergs
authors.forename: Annelies
authors.initials: A
authors.lastname: Peeters
authors.forename: Frank
authors.initials: F
authors.lastname: Jacobs
authors.forename: Marc
authors.initials: M
authors.lastname: Espeel
authors.forename: Peter
authors.initials: P
authors.lastname: Carmeliet
authors.forename: Paul P
authors.initials: PP
authors.lastname: Van Veldhoven
authors.forename: Myriam
authors.initials: M
authors.lastname: Baes
mesh_terms: D052438:Adipocytes, White / Q000378:metabolism* / Q000473:pathology; D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000235:genetics; D050556:Fatty Acid-Binding Proteins / Q000235:genetics*; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology; D009132:Muscles / Q000378:metabolism* / Q000473:pathology; D000074435:Peroxisome-Targeting Signal 1 Receptor; D020675:Peroxisomes / Q000378:metabolism*; D010641:Phenotype; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D012768:Shivering; D015398:Signal Transduction; D013564:Sympathetic Nervous System / Q000378:metabolism / Q000503:physiopathology; D022722:Thermogenesis / Q000235:genetics
chemical_list: C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D007328:Insulin; D020738:Leptin; D000074435:Peroxisome-Targeting Signal 1 Receptor; C000614265:Pex5 protein, mouse; D018160:Receptors, Cytoplasmic and Nuclear