Journal
JOURNAL OF LIPID RESEARCH
Volume 53, Issue 2, Pages 273-281Publisher
ELSEVIER
DOI: 10.1194/jlr.M020628
Keywords
Alzheimer's disease; apolipoprotein E; shotgun lipidomics; sphingolipidomics
Categories
Funding
- National Institute on Aging/National Institute of Diabetes and Digestive and Kidney Diseases [R01 AG-31675]
- LipoSpectrum, LLC
Ask authors/readers for more resources
Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha), 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-1 alpha (PGC-1 alpha(-/-)) 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-1 alpha(-/-) mice compared with WT mice at all ages examined. Chronic caloric restriction (CR) for 22 months essentially restored the sulfatide reduction in PGC-1 alpha(-/-) mice compared with WT, but sulfatide reduction was not restored in PGC-1 alpha(-/-) 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-1 alpha-MAL pathway, whereas the latter is under the control of LXR/RXR-apoE metabolism pathway. These results suggest a novel mechanistic role of PGC-1 alpha in sulfatide homeostasis, provide new insights into the importance of PGC-1 alpha in neurological functions, and indicate a potential therapeutic approach for treatment of deficient PGC-1 alpha-induced alterations in sulfatide homeostasis.-Kiebish, M.A., D.M. Young, J.J. Lehman, and X. Han. Chronic caloric restriction attenuates a loss of sulfatide content in PGC-1 alpha(-/-) mouse cortex: a potential lipidomic role of PGC-1 alpha in neurodegeneration. J. Lipid Res. 2012. 53: 273-281.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available