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Kruppel-like factor 15 regulates skeletal muscle lipid flux and exercise adaptation

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journal contribution
posted on 24.04.2012, 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 Jain
The 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 America

Volume

109

Issue

17

Pagination

6739 - 6744

Publisher

National Academy of Sciences

Location

Washington D.C.

ISSN

0027-8424

eISSN

1091-6490

Language

eng

Publication classification

C1 Refereed article in a scholarly journal

Copyright notice

2012, by the National Academy of Sciences