A Conserved Role for Phosphatidylinositol 3-Kinase but Not Akt Signaling in Mitochondrial Adaptations that Accompany Physiological Cardiac Hypertrophy

Brian T O'Neill; Jaetaek Kim; Adam R Wende; Heather A Theobald; Joseph Tuinei; Jonathan Buchanan; Aili Guo; Vlad G Zaha; Don K Davis; John C Schell; Sihem Boudina; Benjamin Wayment; Sheldon E Litwin; Tetsuo Shioi; Seigo Izumo; Morris J Birnbaum; E. Dale Abel

doi:10.1016/j.cmet.2007.09.001

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A Conserved Role for Phosphatidylinositol 3-Kinase but Not Akt Signaling in Mitochondrial Adaptations that Accompany Physiological Cardiac Hypertrophy

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A Conserved Role for Phosphatidylinositol 3-Kinase but Not Akt Signaling in Mitochondrial Adaptations that Accompany Physiological Cardiac Hypertrophy

Brian T O'Neill, Jaetaek Kim, Adam R Wende, Heather A Theobald, Joseph Tuinei, Jonathan Buchanan, Aili Guo, Vlad G Zaha, Don K Davis, John C Schell, …

Cell metabolism, Vol.6(4), pp.294-306

2007

DOI: 10.1016/j.cmet.2007.09.001

PMID: 17908558

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Abstract

Physiological cardiac hypertrophy is associated with mitochondrial adaptations that are characterized by activation of PGC-1α and increased fatty acid oxidative (FAO) capacity. It is widely accepted that phosphatidylinositol 3-kinase (PI3K) signaling to Akt1 is required for physiological cardiac growth. However, the signaling pathways that coordinate physiological hypertrophy and metabolic remodeling are incompletely understood. We show here that activation of PI3K is sufficient to increase myocardial FAO capacity and that inhibition of PI3K signaling prevents mitochondrial adaptations in response to physiological hypertrophic stimuli despite increased expression of PGC-1α. We also show that activation of the downstream kinase Akt is not required for the mitochondrial adaptations that are secondary to PI3K activation. Thus, in physiological cardiac growth, PI3K is an integrator of cellular growth and metabolic remodeling. Although PI3K signaling to Akt1 is required for cellular growth, Akt-independent pathways mediate the accompanying mitochondrial adaptations.

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Title: Subtitle: A Conserved Role for Phosphatidylinositol 3-Kinase but Not Akt Signaling in Mitochondrial Adaptations that Accompany Physiological Cardiac Hypertrophy
Creators: Brian T O'Neill - Program in Human Molecular Biology and Genetics and Division of Endocrinology, Metabolism, and Diabetes, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
Jaetaek Kim - Program in Human Molecular Biology and Genetics and Division of Endocrinology, Metabolism, and Diabetes, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
Adam R Wende - Program in Human Molecular Biology and Genetics and Division of Endocrinology, Metabolism, and Diabetes, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
Heather A Theobald - Program in Human Molecular Biology and Genetics and Division of Endocrinology, Metabolism, and Diabetes, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
Joseph Tuinei - Program in Human Molecular Biology and Genetics and Division of Endocrinology, Metabolism, and Diabetes, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
Jonathan Buchanan - Program in Human Molecular Biology and Genetics and Division of Endocrinology, Metabolism, and Diabetes, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
Aili Guo - Program in Human Molecular Biology and Genetics and Division of Endocrinology, Metabolism, and Diabetes, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
Vlad G Zaha - Program in Human Molecular Biology and Genetics and Division of Endocrinology, Metabolism, and Diabetes, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
Don K Davis - Program in Human Molecular Biology and Genetics and Division of Endocrinology, Metabolism, and Diabetes, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
John C Schell - Program in Human Molecular Biology and Genetics and Division of Endocrinology, Metabolism, and Diabetes, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
Sihem Boudina - Program in Human Molecular Biology and Genetics and Division of Endocrinology, Metabolism, and Diabetes, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
Benjamin Wayment - Division of Cardiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT 84132, USA
Sheldon E Litwin - Division of Cardiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT 84132, USA
Tetsuo Shioi - Department of Internal Medicine and Cardiology, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan
Seigo Izumo - Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USA
Morris J Birnbaum - Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
E. Dale Abel - Program in Human Molecular Biology and Genetics and Division of Endocrinology, Metabolism, and Diabetes, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
Resource Type: Journal article
Publication Details: Cell metabolism, Vol.6(4), pp.294-306
Publisher: Elsevier Inc
DOI: 10.1016/j.cmet.2007.09.001
PMID: 17908558
ISSN: 1550-4131
eISSN: 1932-7420
Language: English
Date published: 2007
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984025296202771

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