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

First Author  Haldar SM Year  2012
Journal  Proc Natl Acad Sci U S A Volume  109
Issue  17 Pages  6739-44
PubMed ID  22493257 Mgi Jnum  J:183838
Mgi Id  MGI:5319416 Doi  10.1073/pnas.1121060109
Citation  Haldar SM, et al. (2012) Kruppel-like factor 15 regulates skeletal muscle lipid flux and exercise adaptation. Proc Natl Acad Sci U S A 109(17):6739-44
abstractText  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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