Enhancing Cardiac Triacylglycerol Metabolism Improves Recovery From Ischemic Stress

Elevated cardiac triacylglycerol (TAG) content is traditionally equated with cardiolipotoxicity and suggested to be a culprit in cardiac dysfunction. However, previous work demonstrated that myosin heavy-chain–mediated cardiac-specific overexpression of diacylglycerol transferase 1 (MHC-DGAT1), the...

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Main Authors:	Kolwicz, Stephen C., Liu, Li, Goldberg, Ira J., Tian, Rong
Format:	Online
Language:	English
Published:	American Diabetes Association 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4512225/

id	pubmed-4512225
recordtype	oai_dc
spelling	pubmed-45122252016-08-01 Enhancing Cardiac Triacylglycerol Metabolism Improves Recovery From Ischemic Stress Kolwicz, Stephen C. Liu, Li Goldberg, Ira J. Tian, Rong Metabolism Elevated cardiac triacylglycerol (TAG) content is traditionally equated with cardiolipotoxicity and suggested to be a culprit in cardiac dysfunction. However, previous work demonstrated that myosin heavy-chain–mediated cardiac-specific overexpression of diacylglycerol transferase 1 (MHC-DGAT1), the primary enzyme for TAG synthesis, preserved cardiac function in two lipotoxic mouse models despite maintaining high TAG content. Therefore, we examined whether increased cardiomyocyte TAG levels due to DGAT1 overexpression led to changes in cardiac TAG turnover rates under normoxia and ischemia-reperfusion conditions. MHC-DGAT1 mice had elevated TAG content and synthesis rates, which did not alter cardiac function, substrate oxidation, or myocardial energetics. MHC-DGAT1 hearts had ischemia-induced lipolysis; however, when a physiologic mixture of long-chain fatty acids was provided, enhanced TAG turnover rates were associated with improved functional recovery from low-flow ischemia. Conversely, exogenous supply of palmitate during reperfusion suppressed elevated TAG turnover rates and impaired recovery from ischemia in MHC-DGAT1 hearts. Collectively, this study shows that elevated TAG content, accompanied by enhanced turnover, does not adversely affect cardiac function and, in fact, provides cardioprotection from ischemic stress. In addition, the results highlight the importance of exogenous supply of fatty acids when assessing cardiac lipid metabolism and its relationship with cardiac function. American Diabetes Association 2015-08 2015-04-09 /pmc/articles/PMC4512225/ /pubmed/25858561 http://dx.doi.org/10.2337/db14-1943 Text en © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Kolwicz, Stephen C. Liu, Li Goldberg, Ira J. Tian, Rong
spellingShingle	Kolwicz, Stephen C. Liu, Li Goldberg, Ira J. Tian, Rong Enhancing Cardiac Triacylglycerol Metabolism Improves Recovery From Ischemic Stress
author_facet	Kolwicz, Stephen C. Liu, Li Goldberg, Ira J. Tian, Rong
author_sort	Kolwicz, Stephen C.
title	Enhancing Cardiac Triacylglycerol Metabolism Improves Recovery From Ischemic Stress
title_short	Enhancing Cardiac Triacylglycerol Metabolism Improves Recovery From Ischemic Stress
title_full	Enhancing Cardiac Triacylglycerol Metabolism Improves Recovery From Ischemic Stress
title_fullStr	Enhancing Cardiac Triacylglycerol Metabolism Improves Recovery From Ischemic Stress
title_full_unstemmed	Enhancing Cardiac Triacylglycerol Metabolism Improves Recovery From Ischemic Stress
title_sort	enhancing cardiac triacylglycerol metabolism improves recovery from ischemic stress
description	Elevated cardiac triacylglycerol (TAG) content is traditionally equated with cardiolipotoxicity and suggested to be a culprit in cardiac dysfunction. However, previous work demonstrated that myosin heavy-chain–mediated cardiac-specific overexpression of diacylglycerol transferase 1 (MHC-DGAT1), the primary enzyme for TAG synthesis, preserved cardiac function in two lipotoxic mouse models despite maintaining high TAG content. Therefore, we examined whether increased cardiomyocyte TAG levels due to DGAT1 overexpression led to changes in cardiac TAG turnover rates under normoxia and ischemia-reperfusion conditions. MHC-DGAT1 mice had elevated TAG content and synthesis rates, which did not alter cardiac function, substrate oxidation, or myocardial energetics. MHC-DGAT1 hearts had ischemia-induced lipolysis; however, when a physiologic mixture of long-chain fatty acids was provided, enhanced TAG turnover rates were associated with improved functional recovery from low-flow ischemia. Conversely, exogenous supply of palmitate during reperfusion suppressed elevated TAG turnover rates and impaired recovery from ischemia in MHC-DGAT1 hearts. Collectively, this study shows that elevated TAG content, accompanied by enhanced turnover, does not adversely affect cardiac function and, in fact, provides cardioprotection from ischemic stress. In addition, the results highlight the importance of exogenous supply of fatty acids when assessing cardiac lipid metabolism and its relationship with cardiac function.
publisher	American Diabetes Association
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4512225/
_version_	1613251168184565760

Enhancing Cardiac Triacylglycerol Metabolism Improves Recovery From Ischemic Stress

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