Lipid Use and Misuse by the Heart

Schulze, P. Christian; Drosatos, Konstantinos; Goldberg, Ira J.

doi:10.1161/circresaha.116.306842

Cited by 251 publications

(238 citation statements)

References 244 publications

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“…HFrEF patients had the lowest intramyocardial fat amount. Preclinical cardiac cachexia might explain this finding . Myocardial TG was significantly higher in HFpEF women than in men.…”

Section: Discussionmentioning

confidence: 89%

Myocardial adipose deposition and the development of heart failure with preserved ejection fraction

Lee

Hsu

et al. 2019

European J of Heart Fail

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Aims It has been proposed that an increase of myocardial adiposity is related to left ventricular (LV) diastolic dysfunction. The specific roles of myocardial steatosis including epicardial fat and intramyocardial fat for diastolic function are unknown in those patients suffering heart failure (HF) with reduced (HFrEF) or preserved ejection fraction (HFpEF). This study aims to determine the complex relationship between myocardial adiposity in patients with HFrEF or HFpEF. Methods and results Using cardiac magnetic resonance imaging (CMRI), myocardial steatosis was measured in 305 subjects (34 patients with HFrEF, 163 with HFpEF, and 108 non‐HF controls). We also evaluated cardiac structure and diastolic and systolic function by echocardiography and CMRI. Patients with HFpEF had significantly more intramyocardial fat than HFrEF patients or non‐HF controls [intramyocardial fat content (%), 1.56 (1.26, 1.89) vs. 0.75 (0.50, 0.87) and 1.0 (0.79, 1.15), P < 0.05]. Intramyocardial fat amount (%) was higher in HFpEF women than in men [1.91% (1.17%, 2.32%) vs. 1.22 (0.87%, 2.02%), P = 0.01]. When estimated by CMRI (left ventricular peak filling rate), echocardiographic E/e′ level, or left atrial volume index, intramyocardial fat correlated with LV diastolic dysfunction parameters in HFpEF patients, and this was independent of age, co‐morbidities, body mass index, gender, and myocardial fibrosis (standardized coefficient: β = −0.34, P = 0.03; β = 0.29, P = 0.025; and β = 0.25, P = 0.02, respectively). Conclusions Patients with HFpEF had significantly more intramyocardial fat than HFrEF patients or non‐HF controls. Independent of risk factors or gender, intramyocardial fat correlated with LV diastolic dysfunction parameters in HFpEF patients.

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“…HFrEF patients had the lowest intramyocardial fat amount. Preclinical cardiac cachexia might explain this finding . Myocardial TG was significantly higher in HFpEF women than in men.…”

Section: Discussionmentioning

confidence: 89%

Myocardial adipose deposition and the development of heart failure with preserved ejection fraction

Lee

Hsu

et al. 2019

European J of Heart Fail

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“…Recent studies have indicated that diacylglycerol and ceramide, but not TG, are responsible for cardiac lipotoxicity (Schulze et al. ). In addition, several studies have shown protective roles of lipid droplets in cells by storing TGs incorporated from cytotoxic saturated fatty acid (Listenberger et al.…”

Section: Discussionmentioning

confidence: 99%

Empagliflozin normalizes the size and number of mitochondria and prevents reduction in mitochondrial size after myocardial infarction in diabetic hearts

et al. 2018

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To explore mechanisms by which SGLT2 inhibitors protect diabetic hearts from heart failure, we examined the effect of empagliflozin (Empa) on the ultrastructure of cardiomyocytes in the noninfarcted region of the diabetic heart after myocardial infarction (MI). OLETF, a rat model of type 2 diabetes, and its nondiabetic control, LETO, received a sham operation or left coronary artery ligation 12 h before tissue sampling. Tissues were sampled from the posterior ventricle (i.e., the remote noninfarcted region in rats with MI). The number of mitochondria was larger and small mitochondria were more prevalent in OLETF than in LETO. Fis1 expression level was higher in OLETF than in LETO, while phospho‐Ser637‐Drp1, total Drp1, Mfn1/2, and OPA1 levels were comparable. MI further reduced the size of mitochondria with increased Drp1‐Ser616 phosphorylation in OLETF. The number of autophagic vacuoles was unchanged after MI in LETO but was decreased in OLETF. Lipid droplets in cardiomyocytes and tissue triglycerides were increased in OLETF. Empa administration (10 mg/kg per day) reduced blood glucose and triglycerides and paradoxically increased lipid droplets in cardiomyocytes in OLETF. Empa suppressed Fis1 upregulation, increased Bnip3 expression, and prevented reduction in both mitochondrial size and autophagic vacuole number after MI in OLETF. Together with the results of our parallel study showing upregulation of SOD2 and catalase by Empa, the results indicate that Empa normalizes the size and number of mitochondria in diabetic hearts and that diabetes‐induced excessive reduction in mitochondrial size after MI was prevented by Empa via suppression of ROS and restoration of autophagy.

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“…In settings of both T1D and T2D, the heart becomes almost completely reliant upon FAs as a source of energy. Although the mechanisms by which this occurs are (Poornima et al 2006, Goldberg et al 2012, Bayeva et al 2013, Schulze et al 2016). Thus, we will just briefly address the key pathways by which pathological lipid accumulation is thought to contribute toward the development of cardiomyopathy in the setting of diabetes (Fig.…”

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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Lipid Use and Misuse by the Heart

Cited by 251 publications

References 244 publications

Myocardial adipose deposition and the development of heart failure with preserved ejection fraction

Myocardial adipose deposition and the development of heart failure with preserved ejection fraction

Empagliflozin normalizes the size and number of mitochondria and prevents reduction in mitochondrial size after myocardial infarction in diabetic hearts

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

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