Altered mitochondrial metabolism in the insulin resistant heart

Marina Makrecka-Kuka; Edgars Liepinsh; Andrew J Murray; Hélène Lemieux; Maija Dambrova; Kersti Tepp; Marju Puurand; Tuuli Käämbre; Woo Hyun Han; Paul de Goede; Katie A O'Brien; Belma Turan; Erkan Tuncay; Yusuf Olgar; Anabela P Rolo; Carlos M Palmeira; Neoma T Boardman; Rob Ci Wüst; Terje S Larsen

doi:10.1111/apha.13430

Altered mitochondrial metabolism in the insulin resistant heart

Marina Makrecka-Kuka, Edgars Liepinsh, Andrew J Murray, Hélène Lemieux, Maija Dambrova, Kersti Tepp, Marju Puurand, Tuuli Käämbre, Woo Hyun Han, Paul de Goede, Katie A O'Brien, Belma Turan, Erkan Tuncay, Yusuf Olgar, Anabela P Rolo, Carlos M Palmeira, Neoma T Boardman, Rob Ci Wüst, Terje S Larsen

Physiology

Research output: Contribution to Journal › Review article › Academic › peer-review

Abstract

Obesity-induced insulin resistance and type 2 diabetes mellitus can ultimately result in various complications, including diabetic cardiomyopathy. In this case, cardiac dysfunction is characterized by metabolic disturbances such as impaired glucose oxidation and an increased reliance on fatty acid oxidation. Mitochondrial dysfunction has often been associated with the altered metabolic function in the diabetic heart, and may result from fatty acid-induced lipotoxicity and uncoupling of oxidative phosphorylation. In this review, we address the metabolic changes in the diabetic heart, focusing on the loss of metabolic flexibility and cardiac mitochondrial function. We consider the alterations observed in mitochondrial substrate utilization, bioenergetics and dynamics, and highlight new areas of research which may improve our understanding of the cause and effect of cardiac mitochondrial dysfunction in diabetes. Finally, we explore how lifestyle (nutrition and exercise) and pharmacological interventions can prevent and treat metabolic and mitochondrial dysfunction in diabetes.

Original language	English
Article number	e13430
Pages (from-to)	e13430
Journal	Acta Physiologica
Volume	228
Issue number	3
Early online date	16 Dec 2019
DOIs	https://doi.org/10.1111/apha.13430
Publication status	Published - Mar 2020

Bibliographical note

Funding

This publication is based upon work from COST Action CA15203 MITOEAGLE, supported by COST (European Cooperation in Science and Technology). Web site: www.cost.eu . EL was supported by Latvian Council of Science grant project no. lzp‐2018/1‐0082. KT, MP, TK were supported by the institutional research funding IUT23‐1 of the Estonian Ministry of Education and Research.

Funders	Funder number
European Cooperation in Science and Technology	CA15203
Haridus- ja Teadusministeerium
Latvijas Zinātnes Padome	lzp‐2018/1‐0082

Keywords

diabetes
heart
lipotoxicity
mitochondria

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1111/apha.13430

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Makrecka-Kuka, M., Liepinsh, E., Murray, A. J., Lemieux, H., Dambrova, M., Tepp, K., Puurand, M., Käämbre, T., Han, W. H., de Goede, P., O'Brien, K. A., Turan, B., Tuncay, E., Olgar, Y., Rolo, A. P., Palmeira, C. M., Boardman, N. T., Wüst, R. C., & Larsen, T. S. (2020). Altered mitochondrial metabolism in the insulin resistant heart. Acta Physiologica, 228(3), e13430. Article e13430. https://doi.org/10.1111/apha.13430

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abstract = "Obesity-induced insulin resistance and type 2 diabetes mellitus can ultimately result in various complications, including diabetic cardiomyopathy. In this case, cardiac dysfunction is characterized by metabolic disturbances such as impaired glucose oxidation and an increased reliance on fatty acid oxidation. Mitochondrial dysfunction has often been associated with the altered metabolic function in the diabetic heart, and may result from fatty acid-induced lipotoxicity and uncoupling of oxidative phosphorylation. In this review, we address the metabolic changes in the diabetic heart, focusing on the loss of metabolic flexibility and cardiac mitochondrial function. We consider the alterations observed in mitochondrial substrate utilization, bioenergetics and dynamics, and highlight new areas of research which may improve our understanding of the cause and effect of cardiac mitochondrial dysfunction in diabetes. Finally, we explore how lifestyle (nutrition and exercise) and pharmacological interventions can prevent and treat metabolic and mitochondrial dysfunction in diabetes.",

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Makrecka-Kuka, M, Liepinsh, E, Murray, AJ, Lemieux, H, Dambrova, M, Tepp, K, Puurand, M, Käämbre, T, Han, WH, de Goede, P, O'Brien, KA, Turan, B, Tuncay, E, Olgar, Y, Rolo, AP, Palmeira, CM, Boardman, NT, Wüst, RC & Larsen, TS 2020, 'Altered mitochondrial metabolism in the insulin resistant heart', Acta Physiologica, vol. 228, no. 3, e13430, pp. e13430. https://doi.org/10.1111/apha.13430

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AU - Makrecka-Kuka, Marina

AU - Liepinsh, Edgars

AU - Murray, Andrew J

AU - Lemieux, Hélène

AU - Dambrova, Maija

AU - Tepp, Kersti

AU - Puurand, Marju

AU - Käämbre, Tuuli

AU - Han, Woo Hyun

AU - de Goede, Paul

AU - O'Brien, Katie A

AU - Turan, Belma

AU - Tuncay, Erkan

AU - Olgar, Yusuf

AU - Rolo, Anabela P

AU - Palmeira, Carlos M

AU - Boardman, Neoma T

AU - Wüst, Rob Ci

AU - Larsen, Terje S

PY - 2020/3

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AB - Obesity-induced insulin resistance and type 2 diabetes mellitus can ultimately result in various complications, including diabetic cardiomyopathy. In this case, cardiac dysfunction is characterized by metabolic disturbances such as impaired glucose oxidation and an increased reliance on fatty acid oxidation. Mitochondrial dysfunction has often been associated with the altered metabolic function in the diabetic heart, and may result from fatty acid-induced lipotoxicity and uncoupling of oxidative phosphorylation. In this review, we address the metabolic changes in the diabetic heart, focusing on the loss of metabolic flexibility and cardiac mitochondrial function. We consider the alterations observed in mitochondrial substrate utilization, bioenergetics and dynamics, and highlight new areas of research which may improve our understanding of the cause and effect of cardiac mitochondrial dysfunction in diabetes. Finally, we explore how lifestyle (nutrition and exercise) and pharmacological interventions can prevent and treat metabolic and mitochondrial dysfunction in diabetes.

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KW - heart

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Altered mitochondrial metabolism in the insulin resistant heart

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

Access to Document

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