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Publication
Kruppel-like factor 15 regulates skeletal muscle lipid flux and exercise
adaptation.
Authors Haldar SM, Jeyaraj D, Anand P, Zhu H, Lu Y, Prosdocimo DA, Eapen B, Kawanami D,
Okutsu M, Brotto L, Fujioka H, Kerner J, Rosca MG, McGuinness OP, Snow RJ,
Russell AP, Gerber AN, Bai X, Yan Z, Nosek TM, Brotto M, Hoppel CL, Jain MK
Submitted By Submitted Externally on 9/18/2012
Status Published
Journal Proceedings of the National Academy of Sciences of the United States of America
Year 2012
Date Published
Volume : Pages 109 : 6739 - 6744
PubMed Reference 22493257
Abstract 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.




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