Loss of Metabolic Flexibility in the Failing Heart.
TLDR
An increasing body of evidence shows that increasing cardiac ATP production and/or modulating cardiac energy substrate preference positively correlates with heart function and can lead to better outcomes.Abstract:
To maintain its high energy demand the heart is equipped with a highly complex and efficient enzymatic machinery that orchestrates ATP production using multiple energy substrates, namely fatty acids, carbohydrates (glucose and lactate), ketones and amino acids. The contribution of these individual substrates to ATP production can dramatically change, depending on such variables as substrate availability, hormonal status and energy demand. This "metabolic flexibility" is a remarkable virtue of the heart, which allows utilization of different energy substrates at different rates to maintain contractile function. In heart failure, cardiac function is reduced, which is accompanied by discernible energy metabolism perturbations and impaired metabolic flexibility. While it is generally agreed that overall mitochondrial ATP production is impaired in the failing heart, there is less consensus as to what actual switches in energy substrate preference occur. The failing heart shift toward a greater reliance on glycolysis and ketone body oxidation as a source of energy, with a decrease in the contribution of glucose oxidation to mitochondrial oxidative metabolism. The heart also becomes insulin resistant. However, there is less consensus as to what happens to fatty acid oxidation in heart failure. While it is generally believed that fatty acid oxidation decreases, a number of clinical and experimental studies suggest that fatty acid oxidation is either not changed or is increased in heart failure. Of importance, is that any metabolic shift that does occur has the potential to aggravate cardiac dysfunction and the progression of the heart failure. An increasing body of evidence shows that increasing cardiac ATP production and/or modulating cardiac energy substrate preference positively correlates with heart function and can lead to better outcomes. This includes increasing glucose and ketone oxidation and decreasing fatty acid oxidation. In this review we present the physiology of the energy metabolism pathways in the heart and the changes that occur in these pathways in heart failure. We also look at the interventions which are aimed at manipulating the myocardial metabolic pathways toward more efficient substrate utilization which will eventually improve cardiac performance.read more
Citations
More filters
Journal ArticleDOI
Heart Failure in Type 2 Diabetes Mellitus.
Helena Kenny,E. Dale Abel +1 more
TL;DR: The state of knowledge about the impact of existing antihyperglycemic therapies on HF is summarized, potential mechanisms for beneficial or deleterious effects are discussed, and currently approved pharmacological therapies for HF are reviewed.
Journal ArticleDOI
Empagliflozin Increases Cardiac Energy Production in Diabetes: Novel Translational Insights Into the Heart Failure Benefits of SGLT2 Inhibitors.
Subodh Verma,Sonia Rawat,Kim L. Ho,Cory S. Wagg,Liyan Zhang,Hwee Teoh,John E. Dyck,Golam M. Uddin,Gavin Y. Oudit,Eric Mayoux,Michael Lehrke,Nikolaus Marx,Gary D. Lopaschuk +12 more
TL;DR: In this article, the authors evaluated cardiac energy production and bioenergetics in an experimental model of diabetes treated with the SGLT2 inhibitor empagliflozin.
Journal ArticleDOI
Cardiac Energy Metabolism in Heart Failure
TL;DR: In this paper, the effects of metabolic changes that occur in heart failure are complex and are dependent not only on the severity and type of heart failure present but also on the co-existence of common comorbidities such as obesity and type 2 diabetes.
Journal ArticleDOI
Cellular and molecular pathobiology of heart failure with preserved ejection fraction.
Sumita Mishra,David A. Kass +1 more
TL;DR: A review of the cellular and molecular pathobiology of heart failure with preserved ejection fraction (HFpEF) can be found in this paper, with the major focus being on mechanisms relevant to the heart.
Journal ArticleDOI
Glucose Metabolism in Cardiac Hypertrophy and Heart Failure
Diem Hong Tran,Zhao V. Wang +1 more
TL;DR: Recent findings of cardiac metabolic changes in response to hemodynamic stress and cardiac ischemia with a focus on glucose utilization are reviewed and potential therapeutic targets from carbohydrate metabolic pathways to tackle this devastating heart disease are discussed.
References
More filters
Journal ArticleDOI
Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes.
Bernard Zinman,Christoph Wanner,John M. Lachin,David Fitchett,Erich Bluhmki,Stefan Hantel,Michaela Mattheus,Theresa Devins,Odd Erik Johansen,Hans-Juergen Woerle,Uli C. Broedl,Silvio E. Inzucchi +11 more
TL;DR: Patients with type 2 diabetes at high risk for cardiovascular events who received empagliflozin, as compared with placebo, had a lower rate of the primary composite cardiovascular outcome and of death from any cause when the study drug was added to standard care.
Journal ArticleDOI
Heart Disease and Stroke Statistics—2017 Update: A Report From the American Heart Association
Emelia J. Benjamin,Michael J. Blaha,Stephanie E. Chiuve,Mary Cushman,Sandeep R Das,Rajat Deo,Sarah D. de Ferranti,James S. Floyd,Myriam Fornage,Cathleen Gillespie,Carmen R. Isasi,Monik C. Jim'nez,Lori Chaffn Jordan,Suzanne E. Judd,Daniel T. Lackland,Judith H. Lichtman,Lynda D. Lisabeth,Simin Liu,Chris T. Longenecker,Rachel H. Mackey,Kunihiro Matsushita,Dariush Mozaffarian,Michael E. Mussolino,Khurram Nasir,Robert W. Neumar,Latha Palaniappan,Dilip K. Pandey,Ravi R. Thiagarajan,Mathew J. Reeves,Matthew D. Ritchey,Carlos J. Rodriguez,Gregory A. Roth,Wayne D. Rosamond,Comilla Sasson,Amytis Towfghi,Connie W. Tsao,Melanie B. Turner,Salim S. Virani,Jenifer H. Voeks,Joshua Z. Willey,John T. Wilkins,Jason H Y Wu,Heather M. Alger,Sally S. Wong,Paul Muntner +44 more
TL;DR: WRITING GROUP MEMBERS Emelia J. Benjamin, MD, SCM, FAHA Michael J. Reeves, PhD Matthew Ritchey, PT, DPT, OCS, MPH Carlos J. Jiménez, ScD, SM Lori Chaffin Jordan,MD, PhD Suzanne E. Judd, PhD
Journal ArticleDOI
The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus.
Journal ArticleDOI
The failing heart--an engine out of fuel.
TL;DR: This review describes cardiac energy metabolism, appraises the methods used for its assessment, evaluates the role of impaired energy metabolism in heart failure, and gives options for metabolic therapy.