snow-kruppellike-2012.pdf (1.19 MB)
Kruppel-like factor 15 regulates skeletal muscle lipid flux and exercise adaptation
journal contribution
posted on 2012-04-24, 00:00 authored by S Haldar, D Jeyaraj, P Anand, H Zhu, Y Lu, D Prosdocimo, B Eapen, D Kawanami, M Okutsu, L Brotto, H Fujioka, J Kerner, M Rosca, O McGuinness, Rod SnowRod Snow, Aaron RussellAaron Russell, A Gerber, X Bai, Z Yan, T Nosek, M Brotto, C Hoppel, M JainThe ability of skeletal muscle to enhance lipid utilization during exercise is a form of metabolic plasticity essential for survival. Conversely, metabolic inflexibility in muscle can cause organ dysfunction and disease. Although the transcription factor Kruppel-like factor 15 (KLF15) is an important regulator of glucose and amino acid metabolism, its endogenous role in lipid homeostasis and muscle physiology is unknown. Here we demonstrate that KLF15 is essential for skeletal muscle lipid utilization and physiologic performance. KLF15 directly regulates a broad transcriptional program spanning all major segments of the lipid-flux pathway in muscle. Consequently, Klf15-deficient mice have abnormal lipid and energy flux, excessive reliance on carbohydrate fuels, exaggerated muscle fatigue, and impaired endurance exercise capacity. Elucidation of this heretofore unrecognized role for KLF15 now implicates this factor as a central component of the transcriptional circuitry that coordinates physiologic flux of all three basic cellular nutrients: glucose, amino acids, and lipids.
History
Journal
Proceedings of the National Academy of Sciences of the United States of AmericaVolume
109Issue
17Pagination
6739 - 6744Publisher
National Academy of SciencesLocation
Washington D.C.Publisher DOI
Link to full text
ISSN
0027-8424eISSN
1091-6490Language
engPublication classification
C1 Refereed article in a scholarly journalCopyright notice
2012, by the National Academy of SciencesUsage metrics
Categories
No categories selectedKeywords
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC