Kruppel-like factor 15 is required for the cardiac adaptive response to fasting.

Autor:	Sugi K; Case Cardiovascular Research Institute and Harrington Heart & Vascular Institute, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, OH, United States of America.; Department of Medicine, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, OH, United States of America., Hsieh PN; Case Cardiovascular Research Institute and Harrington Heart & Vascular Institute, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, OH, United States of America.; Department of Medicine, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, OH, United States of America.; Department of Pathology, Case Western Reserve University, Cleveland, OH, United States of America., Ilkayeva O; Sarah W. Stedman Nutrition and Metabolism Center, Departments of Medicine and Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, United States of America., Shelkay S; Case Cardiovascular Research Institute and Harrington Heart & Vascular Institute, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, OH, United States of America.; Department of Medicine, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, OH, United States of America., Moroney B; Case Cardiovascular Research Institute and Harrington Heart & Vascular Institute, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, OH, United States of America.; Department of Medicine, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, OH, United States of America., Baadh P; Case Cardiovascular Research Institute and Harrington Heart & Vascular Institute, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, OH, United States of America.; Department of Medicine, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, OH, United States of America., Haynes B; Case Cardiovascular Research Institute and Harrington Heart & Vascular Institute, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, OH, United States of America.; Department of Medicine, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, OH, United States of America., Pophal M; Case Cardiovascular Research Institute and Harrington Heart & Vascular Institute, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, OH, United States of America.; Department of Medicine, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, OH, United States of America., Fan L; Case Cardiovascular Research Institute and Harrington Heart & Vascular Institute, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, OH, United States of America.; Department of Medicine, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, OH, United States of America.; Department of Pathology, Case Western Reserve University, Cleveland, OH, United States of America., Newgard CB; Sarah W. Stedman Nutrition and Metabolism Center, Departments of Medicine and Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, United States of America., Prosdocimo DA; Case Cardiovascular Research Institute and Harrington Heart & Vascular Institute, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, OH, United States of America.; Department of Medicine, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, OH, United States of America., Jain MK; Case Cardiovascular Research Institute and Harrington Heart & Vascular Institute, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, OH, United States of America.; Department of Medicine, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, OH, United States of America.
Jazyk:	angličtina
Zdroj:	PloS one [PLoS One] 2018 Feb 06; Vol. 13 (2), pp. e0192376. Date of Electronic Publication: 2018 Feb 06 (Print Publication: 2018).
DOI:	10.1371/journal.pone.0192376
Abstrakt:	Cardiac metabolism is highly adaptive in response to changes in substrate availability, as occur during fasting. This metabolic flexibility is essential to the maintenance of contractile function and is under the control of a group of select transcriptional regulators, notably the nuclear receptor family of factors member PPARα. However, the diversity of physiologic and pathologic states through which the heart must sustain function suggests the possible existence of additional transcriptional regulators that play a role in matching cardiac metabolism to energetic demand. Here we show that cardiac KLF15 is required for the normal cardiac response to fasting. Specifically, we find that cardiac function is impaired upon fasting in systemic and cardiac specific Klf15-null mice. Further, cardiac specific Klf15-null mice display a fasting-dependent accumulation of long chain acylcarnitine species along with a decrease in expression of the carnitine translocase Slc25a20. Treatment with a diet high in short chain fatty acids relieves the KLF15-dependent long chain acylcarnitine accumulation and impaired cardiac function in response to fasting. Our observations establish KLF15 as a critical mediator of the cardiac adaptive response to fasting through its regulation of myocardial lipid utilization.
Databáze:	MEDLINE
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