Peroxisome deficient aP2–Pex5 knockout mice display impaired white adipocyte and muscle function concomitant with reduced adrenergic tone
| Autor: | Peter Carmeliet, Paul P. Van Veldhoven, Frank Jacobs, Katrin Martens, Myriam Baes, Astrid Bottelbergs, Marc Espeel, Annelies Peeters |
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| Rok vydání: | 2012 |
| Předmět: |
Leptin
medicine.medical_specialty Sympathetic Nervous System Peroxisome-Targeting Signal 1 Receptor Adipose Tissue White Endocrinology Diabetes and Metabolism Adipocytes White Receptors Cytoplasmic and Nuclear Adrenergic Adipose tissue White adipose tissue Biology Fatty Acid-Binding Proteins Biochemistry Mice Endocrinology Internal medicine Conditional gene knockout Brown adipose tissue Peroxisomes Genetics medicine Animals Insulin Lipolysis Muscle Skeletal Molecular Biology Inflammation Mice Knockout Muscles Body Weight Shivering Skeletal muscle Thermogenesis Phenotype medicine.anatomical_structure Signal Transduction |
| Zdroj: | Molecular Genetics and Metabolism. 107:735-747 |
| ISSN: | 1096-7192 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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