CD36 as a target to prevent cardiac lipotoxicity and insulin resistance

Glatz, Jan F. C.; Angın, Yeliz; Steinbusch, Laura K. M.; Schwenk, Robert W.; Luiken, Joost J. F. P.

doi:10.1016/j.plefa.2012.04.009

Cited by 45 publications

(42 citation statements)

References 38 publications

(49 reference statements)

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“…In further support of vesicular trafficking of CD36, its sarcolemmal recruitment was shown to involve vesicle-associated membrane proteins (VAMPs) (79). In insulin resistant human muscle, CD36 trafficking is disrupted with chronic relocation of CD36 to the sarcolemma (24, 27) which associates with FA accumulation.…”

Section: Cd36 Influences Heart Ca++ Dynamics and Functional Adaptatiomentioning

confidence: 99%

Structure-Function of CD36 and Importance of Fatty Acid Signal Transduction in Fat Metabolism

et al. 2014

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CD36 is a scavenger receptor that functions in high affinity tissue uptake of long chain fatty acids (FA) and contributes under excessive fat supply to lipid accumulation and metabolic dysfunction. This review describes recent evidence regarding the CD36 FA binding site and a potential mechanism for FA transfer. It also presents the view that CD36 and FA signaling coordinate fat utilization based on newly identified CD36 actions that involve oral fat perception, intestinal fat absorption, secretion of the peptides cholecystokinin and secretin, regulation of hepatic lipoprotein output, activation of beta oxidation by muscle and regulation of the production of the FA derived bioactive eicosanoids. Thus abnormalities of fat metabolism and the associated pathology might involve dysfunction of CD36-mediated signal transduction in addition to the changes of FA uptake.

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Section: Cd36 Influences Heart Ca++ Dynamics and Functional Adaptatiomentioning

confidence: 99%

Structure-Function of CD36 and Importance of Fatty Acid Signal Transduction in Fat Metabolism

et al. 2014

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“…Therefore, cardiomyocytes acquire FAs from the circulation or from hydrolysis of stored lipids (Fig. 1 (Glatz et al 2013), and CD36 has been shown to be necessary for the development of lipotoxic cardiomyopathy in mice (Yang et al 2007). In humans, CD36 deficiency is associated with reduced myocardial FA uptake (Kusaka et al 2008).…”

Section: Lipid Metabolism and Diabetic Cardiomyopathymentioning

confidence: 99%

Lipid metabolism and its implications for type 1 diabetes-associated cardiomyopathy

Ritchie

Zerenturk

Prakoso

et al. 2017

Journal of Molecular Endocrinology

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Diabetic cardiomyopathy was first defined over four decades ago. It was observed in small post-mortem studies of diabetic patients who suffered from concomitant heart failure despite the absence of hypertension, coronary disease or other likely causal factors, as well as in large population studies such as the Framingham Heart Study. Subsequent studies continue to demonstrate an increased incidence of heart failure in the setting of diabetes independent of established risk factors, suggesting direct effects of diabetes on the myocardium. Impairments in glucose metabolism and handling receive the majority of the blame. The role of concomitant impairments in lipid handling, particularly at the level of the myocardium, has however received much less attention. Cardiac lipid accumulation commonly occurs in the setting of type 2 diabetes and has been suggested to play a direct causal role in the development of cardiomyopathy and heart failure in a process termed as cardiac lipotoxicity. Excess lipids promote numerous pathological processes linked to the development of cardiomyopathy, including mitochondrial dysfunction and inflammation. Although somewhat underappreciated, cardiac lipotoxicity also occurs in the setting of type 1 diabetes. This phenomenon is, however, largely understudied in comparison to hyperglycaemia, which has been widely studied in this context. The current review addresses the changes in lipid metabolism occurring in the type 1 diabetic heart and how they are implicated in disease progression. Furthermore, the pathological pathways linked to cardiac lipotoxicity are discussed. Finally, we consider novel approaches for modulating lipid metabolism as a cardioprotective mechanism against cardiomyopathy and heart failure.

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“…CD36, the main fatty acid transporter molecule, facilitates fatty acid uptake by being recruited to the sarcolemma from the intracellular compartment (20)(21)(22)(23). This molecule plays a role in the pathogenesis of various cardiac metabolic diseases, including alterations in cellular lipid metabolism (cardiac lipotoxicity) leading to cardiac contractile dysfunction (24)(25)(26). We tested the presence of CD36 in lipid accumulation in BMPR2 mutant H9c2 cells.…”

Section: Characterization Of H9c2 Cellsmentioning

confidence: 99%

Mechanisms of Lipid Accumulation in the Bone Morphogenetic Protein Receptor Type 2 Mutant Right Ventricle

Talati

Brittain²,

Fessel

et al. 2016

Am J Respir Crit Care Med

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Rationale: In heritable pulmonary arterial hypertension with germline mutation in the bone morphogenetic protein receptor type 2 (BMPR2) gene, right ventricle (RV) dysfunction is associated with RV lipotoxicity; however, the underlying mechanism for lipid accumulation is not known.Objectives: We hypothesized that lipid accumulation in cardiomyocytes with BMPR2 mutation occurs owing to alterations in lipid transport and impaired fatty acid oxidation (FAO), which is exacerbated by a high-lipid (Western) diet (WD).Methods: We used a transgenic mouse model of pulmonary arterial hypertension with mutant BMPR2 and generated a cardiomyocyte cell line with BMPR2 mutation. Electron microscopy and metabolomic analysis were performed on mouse RVs.Measurements and Main Results: By metabolomics analysis, we found an increase in long-chain fatty acids in BMPR2 mutant mouse RVs compared with controls, which correlated with cardiac index. BMPR2-mutant cardiomyocytes had increased lipid compared with controls. Direct measurement of FAO in the WD-fed BMPR2-mutant RV showed impaired palmitate-linked oxygen consumption, and metabolomics analysis showed reduced indices of FAO. Using both mutant BMPR2 mouse RVs and cardiomyocytes, we found an increase in the uptake of 14 C-palmitate and fatty acid transporter CD36 that was further exacerbated by WD.Conclusions: Taken together, our data suggest that impaired FAO and increased expression of the lipid transporter CD36 are key mechanisms underlying lipid deposition in the BMPR2-mutant RV, which are exacerbated in the presence of dietary lipids. These findings suggest important features leading to RV lipotoxicity in pulmonary arterial hypertension and may point to novel areas of therapeutic intervention.

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CD36 as a target to prevent cardiac lipotoxicity and insulin resistance

Cited by 45 publications

References 38 publications

Structure-Function of CD36 and Importance of Fatty Acid Signal Transduction in Fat Metabolism

Structure-Function of CD36 and Importance of Fatty Acid Signal Transduction in Fat Metabolism

Lipid metabolism and its implications for type 1 diabetes-associated cardiomyopathy

Mechanisms of Lipid Accumulation in the Bone Morphogenetic Protein Receptor Type 2 Mutant Right Ventricle

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