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J Biol Chem. 2014 Feb 28;289(9):5914-24. doi: 10.1074/jbc.M113.531384. Epub 2014 Jan 8.

Kruppel-like factor 15 is a critical regulator of cardiac lipid metabolism.

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1
From the Case Cardiovascular Research Institute and Harrington Heart and Vascular Institute.

Abstract

The mammalian heart, the body's 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.

KEYWORDS:

Cardiac Metabolism; Cardiovascular; Kruppel-like Factor (KLF); Lipid Metabolism; Transcription Factors

PMID:
24407292
PMCID:
PMC3937660
DOI:
10.1074/jbc.M113.531384
[Indexed for MEDLINE]
Free PMC Article

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