Kruppel-like Factor 15 Is a Critical Regulator of Cardiac Lipid Metabolism

Background: Metabolic homeostasis is central to normal cardiac function. The molecular mechanisms underlying metabolic plasticity in the heart remain poorly understood. Results: Kruppel-like factor 15 (KLF15) is a direct and independent regulator of myocardial lipid flux. Conclusion: KLF15 is a core component of the transcriptional circuitry that governs cardiac metabolism. Significance: This work is the first to implicate the KLF transcription factor family in cardiac metabolism. The mammalian heart, the body\u27s largest energy consumer, has evolved robust mechanisms to tightly couple fuel supply with energy demand across a wide range of physiologic and pathophysiologic states, yet, when compared with other organs, relatively little is known about the molecular machinery that directly governs metabolic plasticity in the heart. Although previous studies have defined Kruppel-like factor 15 (KLF15) as a transcriptional repressor of pathologic cardiac hypertrophy, a direct role for the KLF family in cardiac metabolism has not been previously established. We show in human heart samples that KLF15 is induced after birth and reduced in heart failure, a myocardial expression pattern that parallels reliance on lipid oxidation. Isolated working heart studies and unbiased transcriptomic profiling in Klf15-deficient hearts demonstrate that KLF15 is an essential regulator of lipid flux and metabolic homeostasis in the adult myocardium. An important mechanism by which KLF15 regulates its direct transcriptional targets is via interaction with p300 and recruitment of this critical co-activator to promoters. This study establishes KLF15 as a key regulator of myocardial lipid utilization and is the first to implicate the KLF transcription factor family in cardiac metabolism

Numerical Studies of Three and Four HAWT Array Using LES and IDDES

The use of wind farms has been growing significantly in the past decades. However, harvesting the wind energy, from wind turbine farms poses significant challenges associated with the complex fluid dynamics such as wind turbine wake flow, wind-tower interactions, blade-wake interactions, etc. The present studies concern the aerodynamics and aeroacoustics studies of HAWT arranged in a 3 and 4 four array configuration. The computational studies are performed using the large-eddy simulation (LES) and improved delayed detached eddy simulation (IDDES) approach. The simulations were performed for a Reynolds number, Re = 1.2 x 105 based on the NACA0012 airfoil chord and free-stream velocity. The results show that the LES and IDDES approaches capture very well the flow physics associated with the wind turbine