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

Haldar, Saptarsi M., Jeyaraj, Darwin, Anand, Priti, Zhu, Han, Lu, Yuan, Prosdocimo, Domenick A., Eapen, Betty, Kawanami, Daiji, Okutsu, Mitsuharu, Brotto, Leticia, Fujioka, Hisashi, Kerner, Janos, Rosca, Mariana G., McGuinness, Owen P., Snow, Rod J., Russell, Aaron P., Gerber, Anthony N., Bai, Xiaodong, Yan, Zhen, Nosek, Thomas M., Brotto, Marco, Hoppel, Charles L. and Jain, Mukesh K. 2012, Kruppel-like factor 15 regulates skeletal muscle lipid flux and exercise adaptation, Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. 17, pp. 6739-6744.

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Title Kruppel-like factor 15 regulates skeletal muscle lipid flux and exercise adaptation
Author(s) Haldar, Saptarsi M.
Jeyaraj, Darwin
Anand, Priti
Zhu, Han
Lu, Yuan
Prosdocimo, Domenick A.
Eapen, Betty
Kawanami, Daiji
Okutsu, Mitsuharu
Brotto, Leticia
Fujioka, Hisashi
Kerner, Janos
Rosca, Mariana G.
McGuinness, Owen P.
Snow, Rod J.
Russell, Aaron P.
Gerber, Anthony N.
Bai, Xiaodong
Yan, Zhen
Nosek, Thomas M.
Brotto, Marco
Hoppel, Charles L.
Jain, Mukesh K.
Journal name Proceedings of the National Academy of Sciences of the United States of America
Volume number 109
Issue number 17
Start page 6739
End page 6744
Total pages 6
Publisher National Academy of Sciences
Place of publication Washington D.C.
Publication date 2012-04-24
ISSN 0027-8424
1091-6490
Keyword(s) fat
mitochondria
myocyte
zinc finger
insulin sensitivity
endurance exercise
energy-metabolism
fat-metabolism
obesity
Summary 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.
Language eng
Field of Research 111699 Medical Physiology not elsewhere classified
Socio Economic Objective 970106 Expanding Knowledge in the Biological Sciences
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2012, by the National Academy of Sciences
Persistent URL http://hdl.handle.net/10536/DRO/DU:30046187

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Created: Mon, 23 Jul 2012, 13:39:12 EST by Jane Moschetti

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