Chronic caloric restriction attenuates a loss of sulfatide content in PGC-1α mouse cortex: a potential lipidomic role of PGC-1α in neurodegeneration
| Autor: | John J. Lehman, Dee M. Young, Xianlin Han, Michael A. Kiebish |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Apolipoprotein E
medicine.medical_specialty Proteolipids QD415-436 Oxidative phosphorylation Biology Biochemistry sphingolipidomics Mice Apolipoproteins E Endocrinology Internal medicine medicine Animals Homeostasis Receptor Liver X receptor shotgun lipidomics Cerebroside-Sulfatase Research Articles apolipoprotein E Caloric Restriction Liver X Receptors Cerebral Cortex Sulfoglycosphingolipids Myelin and Lymphocyte-Associated Proteolipid Proteins Neurodegeneration Membrane Transport Proteins Neurodegenerative Diseases Cell Biology Shotgun lipidomics Alzheimer's disease Lipidome Orphan Nuclear Receptors medicine.disease Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Mice Mutant Strains Enzymes Retinoid X Receptors Trans-Activators Sulfotransferases Myelin Proteins Transcription Factors |
| Zdroj: | Journal of Lipid Research, Vol 53, Iss 2, Pp 273-281 (2012) |
| ISSN: | 0022-2275 |
| Popis: | Peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), a key regulator of energy metabolism and lipid homeostasis in multiple highly oxidative tissues, has been implicated in the metabolic derangements of diabetes and obesity. However, relatively less is known regarding its role in neurological functions. Using shotgun lipidomics, we investigated the lipidome of mouse cerebral cortex with generalized deficiency of PGC-1α (PGC-1α(-/-)) versus wild-type (WT) mice under standard diet and chronically calorically restricted conditions. Specific deficiency in sulfatide, a myelin-specific lipid class critically involved in maintaining neurological function, was uncovered in the cortex of PGC-1α(-/-) mice compared with WT mice at all ages examined. Chronic caloric restriction (CR) for 22 months essentially restored the sulfatide reduction in PGC-1α(-/-) mice compared with WT, but sulfatide reduction was not restored in PGC-1α(-/-) with CR for a short term (i.e., 3 months). Mechanistic studies uncovered and differentiated the biochemical mechanisms underpinning the two conditions of altered sulfatide homeostasis. The former is modulated through PGC-1α-MAL pathway, whereas the latter is under the control of LXR/RXR-apoE metabolism pathway. These results suggest a novel mechanistic role of PGC-1α in sulfatide homeostasis, provide new insights into the importance of PGC-1α in neurological functions, and indicate a potential therapeutic approach for treatment of deficient PGC-1α-induced alterations in sulfatide homeostasis. |
| Databáze: | OpenAIRE |
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