Cell Death and Heart Failure in Obesity: Role of Uncoupling Proteins

Ruiz-Ramírez, Angélica; López-Acosta, Ocarol; Barrios-Maya, Miguel Angel; El-Hafidi, Mohammed

doi:10.1155/2016/9340654

Cited by 42 publications

(25 citation statements)

References 115 publications

(111 reference statements)

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“…Under pathological conditions, some protons return into the matrix while bypassing F0F1 via uncoupling proteins (UCPs) located in the inner mitochondrial membrane [ 43 ]. This results in OXPHOS uncoupling—the dissociation of ATP synthesis from O 2 consumption in the mitochondria.…”

Section: Oxidative Phosphorylation Disorders Of Myocardial Mitochomentioning

confidence: 99%

Involvement of Mitochondrial Disorders in Septic Cardiomyopathy

Durand

Duburcq

Dekeyser

et al. 2017

Oxidative Medicine and Cellular Longevity

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Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. It remains a leading cause of death worldwide, despite the development of various therapeutic strategies. Cardiac dysfunction, also referred to as septic cardiomyopathy, is a frequent and well-described complication of sepsis and associated with worse clinical outcomes. Recent research has increased our understanding of the role of mitochondrial dysfunction in the pathophysiology of septic cardiomyopathy. The purpose of this review is to present this evidence as a coherent whole and to highlight future research directions.

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Section: Oxidative Phosphorylation Disorders Of Myocardial Mitochomentioning

confidence: 99%

Involvement of Mitochondrial Disorders in Septic Cardiomyopathy

Durand

Duburcq

Dekeyser

et al. 2017

Oxidative Medicine and Cellular Longevity

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“…Having successfully established an in vitro model to study the effects of UCP-2 in isolated heart muscle cells by small interfering RNA, we proceeded to identify potential mechanisms by which UCP-2 may affect cardiac hypertrophy and failure. In general, high levels of UCP-2 should reduce ROS formation in the heart by lowering the mitochondrial membrane potential and therefore must be considered as a protective measure [27,28]. Additionally, UCP-2 was found to be activated by ROS [29].…”

Section: Discussionmentioning

confidence: 99%

Alterations in Glucose Metabolism During the Transition to Heart Failure: The Contribution of UCP-2

Kutsche

Schreckenberg

Weber

et al. 2020

Cells

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The cardiac expression of the mitochondrial uncoupling protein (UCP)-2 is increased in patients with heart failure. However, the underlying causes as well as the possible consequences of these alterations during the transition from hypertrophy to heart failure are still unclear. To investigate the role of UCP-2 mechanistically, expression of UCP-2 was silenced by small interfering RNA in adult rat ventricular cardiomyocytes. We demonstrate that a downregulation of UCP-2 by siRNA in cardiomyocytes preserves contractile function in the presence of angiotensin II. Furthermore, silencing of UCP-2 was associated with an upregulation of glucose transporter type (Glut)-4, increased glucose uptake, and reduced intracellular lactate levels, indicating improvement of the oxidative glucose metabolism. To study this adaptation in vivo, spontaneously hypertensive rats served as a model for cardiac hypertrophy due to pressure overload. During compensatory hypertrophy, we found low UCP-2 levels with an upregulation of Glut-4, while the decompensatory state with impaired function was associated with an increase of UCP-2 and reduced Glut-4 expression. By blocking the aldosterone receptor with spironolactone, both cardiac function as well as UCP-2 and Glut-4 expression levels of the compensated phase could be preserved. Furthermore, we were able to confirm this by left ventricular (LV) biopsies of patients with end-stage heart failure. The results of this study show that UCP-2 seems to impact the cardiac glucose metabolism during the transition from hypertrophy to failure by affecting glucose uptake through Glut-4. We suggest that the failing heart could benefit from low UCP-2 levels by improving the efficiency of glucose oxidation. For this reason, UCP-2 inhibition might be a promising therapeutic strategy to prevent the development of heart failure.

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“…In obesity, excessive consumption of foods rich in carbohydrates and excessive release of FAs by adipose tissue both exceed the storage limit and the capacity of oxidation in different tissues . In this regard, FAs are redirected to harmful non‐oxidative metabolic pathways, which are linked with the intracellular accumulation of toxic metabolites such as reactive oxygen species (ROS) …”

Section: Metabolism Of Fatty Acids and Cellular Mechanisms During Injurymentioning

confidence: 99%

Lipotoxicity, neuroinflammation, glial cells and oestrogenic compounds

Hidalgo-Lanussa

Baez‐Jurado

Echeverrı́a

et al. 2019

J Neuroendocrinology

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The high concentrations of free fatty acids as a consequence of obesity and being overweight have become risk factors for the development of different diseases, including neurodegenerative ailments. Free fatty acids are strongly related to inflammatory events, causing cellular and tissue alterations in the brain, including cell death, deficits in neurogenesis and gliogenesis, and cognitive decline. It has been reported that people with a high body mass index have a higher risk of suffering from Alzheimer's disease. Hormones such as oestradiol not only have beneficial effects on brain tissue, but also exert some adverse effects on peripheral tissues, including the ovary and breast. For this reason, some studies have evaluated the protective effect of oestrogen receptor (ER) agonists with more specific tissue activities, such as the neuroactive steroid tibolone. Activation of ERs positively affects the expression of pro‐survival factors and cell signalling pathways, thus promoting cell survival. This review aims to discuss the relationship between lipotoxicity and the development of neurodegenerative diseases. We also elaborate on the cellular and molecular mechanisms involved in neuroprotection induced by oestrogens.

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Cell Death and Heart Failure in Obesity: Role of Uncoupling Proteins

Cited by 42 publications

References 115 publications

Involvement of Mitochondrial Disorders in Septic Cardiomyopathy

Involvement of Mitochondrial Disorders in Septic Cardiomyopathy

Alterations in Glucose Metabolism During the Transition to Heart Failure: The Contribution of UCP-2

Lipotoxicity, neuroinflammation, glial cells and oestrogenic compounds

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