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Lipotoxic cardiomyopathy

Minae An, Dong-Ryeol Ryu, Jang Won Park, Ji Ha Choi, Eun-Mi Park, Kyung Eun Lee, Minna Woo, Minsuk Kim
Aims: Autophagy is essential to maintain tissue homeostasis, particularly in long-lived cells such as cardiomyocytes. Whereas many studies support the importance of autophagy in the mechanisms underlying obesity-related cardiac dysfunction, the role of autophagy in cardiac lipid metabolism remains unclear. In the heart, lipotoxicity is exacerbated by cardiac lipoprotein lipase (LPL), which mediates accumulation of fatty acids to the heart through intravascular triglyceride (TG) hydrolysis...
April 17, 2017: Cardiovascular Research
Rebecca H Ritchie, Eser J Zerenturk, Darnel Prakoso, Anna C Calkin
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...
May 2017: Journal of Molecular Endocrinology
C Y Chen, Y F Huang, Y J Ko, Y J Liu, Y H Chen, R L Walzem, S E Chen
Feed intake is typically restricted (R) in broiler hens to avoid obesity and improve egg production and livability. To determine whether improved heart health contributes to improved livability, fully adult 45-week-old R hens were allowed to consume feed to appetite (ad libitum; AL) up to 10 wk (70 d). Mortality, contractile functions, and morphology at 70 d, and measurements of cardiac hypertrophic remodeling at 7 d and 21 d were made and compared between R and AL hens. Outcomes for cardiac electrophysiology and mortality, reported separately, found increased mortality in AL hens in association with cardiac pathological hypertrophy and contractile dysfunction...
February 22, 2017: Poultry Science
Amedeo Lonardo, Fabio Nascimbeni, Giovanni Targher, Mauro Bernardi, Ferruccio Bonino, Elisabetta Bugianesi, Alessandro Casini, Amalia Gastaldelli, Giulio Marchesini, Fabio Marra, Luca Miele, Filomena Morisco, Salvatore Petta, Fabio Piscaglia, Gianluca Svegliati-Baroni, Luca Valenti, Stefano Bellentani
This review summarizes our current understanding of nonalcoholic fatty liver disease (NAFLD), a multi-factorial systemic disease resulting from a complex interaction between a specific genetic background and multiple environmental/metabolic "hits". The role of gut microbiota, lipotoxicity, inflammation and their molecular pathways is reviewed in-depth. We also discuss the epidemiology and natural history of NAFLD by pinpointing the remarkably high prevalence of NAFLD worldwide and its inherent systemic complications: hepatic (steatohepatitis, advanced fibrosis and cirrhosis), cardio-metabolic (cardiovascular disease, cardiomyopathy, arrhythmias and type 2 diabetes) and neoplastic (primary liver cancers and extra-hepatic cancers)...
January 23, 2017: Digestive and Liver Disease
Michael Joubert, Benoît Jagu, David Montaigne, Xavier Marechal, Angela Tesse, Audrey Ayer, Lucile Dollet, Cédric Le May, Gilles Toumaniantz, Alain Manrique, Flavien Charpentier, Bart Staels, Jocelyne Magré, Bertrand Cariou, Xavier Prieur
Type 2 diabetes mellitus (T2DM) is a well-recognized independent risk factor for heart failure. T2DM is associated with altered cardiac energy metabolism, leading to ectopic lipid accumulation and glucose overload, the exact contribution of these two parameters remaining unclear. To provide new insight into the mechanism driving the development of diabetic cardiomyopathy, we studied a unique model of T2DM: lipodystrophic Bscl2(-/-) (seipin knockout [SKO]) mice. Echocardiography and cardiac magnetic resonance imaging revealed hypertrophic cardiomyopathy with left ventricular dysfunction in SKO mice, and these two abnormalities were strongly correlated with hyperglycemia...
April 2017: Diabetes
Runmin Guo, Zijun Wu, Jiamei Jiang, Chang Liu, Bin Wu, Xingyue Li, Teng Li, Hailiang Mo, Songjian He, Shanghai Li, Hai Yan, Ruina Huang, Qiong You, Keng Wu
OBJECTIVE: To investigate the roles and mechanisms of endogenous hydrogen sulfide (H2S) and endoplasmic reticulum (ER) stress in the development of diabetic cardiomyopathy (DCM). METHODS: Blood of DCM patients included in the study were collected. The model of DCM rats was established using streptozotocin (STZ) injection. Cardiac lipotoxicity in vitro models were established using 500μM palmitic acid (PA) treatment for 24h in AC16 cardiomyocytes. Endogenous H2S production in plasma, culture supernatant and heart was measured by sulphur ion-selective electrode assay...
November 18, 2016: Mechanisms of Ageing and Development
Ismael González-García, Johan Fernø, Carlos Diéguez, Rubén Nogueiras, Miguel López
Hypothalamic lipid metabolism plays a major role in the physiological regulation of energy balance. Modulation of several enzymatic activities that control lipid biosynthesis, such as fatty acid synthase and AMP-activated protein kinase, impacts both feeding and energy expenditure. However, lipids can also cause pathological alterations in the hypothalamus. Lipotoxicity is promoted by excess lipids in tissues not suitable for their storage. A large amount of evidence has demonstrated that lipotoxicity is a pathophysiological mechanism leading to metabolic diseases such as insulin resistance, cardiomyopathy, atherosclerosis, and steatohepatitis...
2017: Neuroendocrinology
Hua Qin, Yan Zhang, Ru Wang, Xiaoyan Du, Liping Li, Haiwei Du
Puerarin, a type of isoflavone, was shown to have multiple protective effects on myocardial injury. The objective of this study was to investigate the role of puerarin in the progression of lipotoxic cardiomyopathy. Primary cardiomyocytes were isolated from FATP1 transgenic (Tg) mice with lipotoxic cardiomyopathy, and various concentrations of puerarin were used to incubate with the cardiomyocytes. Our results showed low-dose puerarin (≤20 μM) treatment increased the cell viability and decreased the accumulation of free fatty acid (FFA)...
December 2016: Journal of Cardiovascular Pharmacology
Konstantinos Drosatos
Age-related cardiomyopathy accounts for a significant part of heart failure cases. Imbalance of the energetic equilibrium of the heart along with mitochondrial dysfunction and impaired β-adrenergic receptor signaling contributes in the aggravation of cardiac function in the elderly. In this review article, studies that correlate cardiac aging with lipotoxicity are summarized. The involvement of inhibition of peroxisome proliferator-activated receptor-α, β-adrenergic receptor desensitization, and mitochondrial dysfunction as underlying mechanisms for the lipid-driven age-related cardiomyopathy are presented with the aim to indicate potential therapeutic targets for cardiac aging...
2016: Pathobiology of Aging & Age related Diseases
Shengcun Li, Lulu Zhang, Rui Ni, Ting Cao, Dong Zheng, Sidong Xiong, Peter A Greer, Guo-Chang Fan, Tianqing Peng
Diabetes and obesity are prevalent in westernized countries. In both conditions, excessive fatty acid uptake by cardiomyocytes induces cardiac lipotoxicity, an important mechanism contributing to diabetic cardiomyopathy. This study investigated the effect of calpain disruption on cardiac lipotoxicity. Cardiac-specific capns1 knockout mice and their wild-type littermates (male, age of 4weeks) were fed a high fat diet (HFD) or normal diet for 20weeks. HFD increased body weight, altered blood lipid profiles and impaired glucose tolerance comparably in both capns1 knockout mice and their wild-type littermates...
November 2016: Biochimica et Biophysica Acta
Peng Cheng, Fangfang Zhang, Lechu Yu, Xiufei Lin, Luqing He, Xiaokun Li, Xuemian Lu, Xiaoqing Yan, Yi Tan, Chi Zhang
Cardiovascular disease (CVD) is one of the most severe diseases in clinics. Fibroblast growth factor 21 (FGF21) is regarded as an important metabolic regulator playing a therapeutic role in diabetes and its complications. The heart is a key target as well as a source of FGF21 which is involved in heart development and also induces beneficial effects in CVDs. Our review is to clarify the roles of FGF21 in CVDs. Strong evidence showed that the development of CVDs including atherosclerosis, coronary heart disease, myocardial ischemia, cardiac hypertrophy, and diabetic cardiomyopathy is associated with serum FGF21 levels increase which was regarded as a compensatory response to induced cardiac protection...
2016: Journal of Diabetes Research
Kenneth D'Souza, Carine Nzirorera, Petra C Kienesberger
The heart balances uptake, metabolism and oxidation of fatty acids (FAs) to maintain ATP production, membrane biosynthesis and lipid signaling. Under conditions where FA uptake outpaces FA oxidation and FA sequestration as triacylglycerols in lipid droplets, toxic FA metabolites such as ceramides, diacylglycerols, long-chain acyl-CoAs, and acylcarnitines can accumulate in cardiomyocytes and cause cardiomyopathy. Moreover, studies using mutant mice have shown that dysregulation of enzymes involved in triacylglycerol, phospholipid, and sphingolipid metabolism in the heart can lead to the excess deposition of toxic lipid species that adversely affect cardiomyocyte function...
October 2016: Biochimica et Biophysica Acta
Jing Liu, Hui Fu, Fen Chang, Jinlan Wang, Shangli Zhang, Yi Caudle, Jing Zhao, Deling Yin
Elevated circulatory free fatty acids (FFAs) especially saturated FFAs, such as palmitate (PA), are detrimental to the heart. However, mechanisms responsible for this phenomenon remain unknown. Here, the role of JAK2/STAT3 in PA-induced cytotoxicity was investigated in cardiomyocytes. We demonstrate that PA suppressed the JAK2/STAT3 pathway by dephosphorylation of JAK2 (Y1007/1008) and STAT3 (Y705), and thus blocked the translocation of STAT3 into the nucleus. Conversely, phosphorylation of S727, another phosphorylated site of STAT3, was increased in response to PA treatment...
May 2016: Apoptosis: An International Journal on Programmed Cell Death
Igor Zlobine, Keshav Gopal, John R Ussher
Patients with type 2 diabetes (T2D) are at increased risk for cardiovascular diseases including diabetic cardiomyopathy, which is ventricular dysfunction independent of underlying coronary artery disease and/or hypertension. With numerous advancements in our ability to detect ventricular dysfunction, as well as the molecular mechanisms contributing to ventricular dysfunction in diabetic patients, it is now appreciated that diabetic cardiomyopathy is becoming more prevalent in our population. In spite of these advancements, we do not have any specific therapies currently approved for treating this condition...
October 2016: Biochimica et Biophysica Acta
T Haffar, F Bérubé-Simard, N Bousette
A major cause for diabetic cardiomyopathy is excess lipid accumulation. To elucidate mechanisms of lipotoxicity mediated diabetic heart disease we need to further our understanding of how lipid metabolism is altered in the diabetic heart. Here we investigated the role of lipid clearance by oxidation as a regulator of lipid-mediated toxicity (lipotoxicity). We evaluated the effect of pre-treating rat neonatal cardiomyocytes (NCMs) with either oleate (mono-unsaturated fatty acid) or palmitate (saturated fatty acid) on fatty acid oxidation (FAO) by measuring (14)C-CO2 production...
December 4, 2015: Biochemical and Biophysical Research Communications
Denis J Glenn, Michelle C Cardema, David G Gardner
Previous studies demonstrated that the liganded vitamin D receptor (VDR) plays an important role in controlling cardiovascular homeostasis. Both the whole animal VDR gene knockout (VDR(-/-)) and the myocyte-specific VDR gene deletion result in changes in cardiac structure and function. Clinical states associated with cardiac steatosis (obesity and diabetes mellitus) are also associated with low circulating 25 OH vitamin D levels. We, therefore, examined the effects of VDR deficiency (VDR(-/-) mouse) in a murine model of cardiac steatosis that expresses the terminal enzyme involved in triglyceride synthesis, diacylglycerol acyltransferase 1 (DGAT1), selectively in the cardiac myocyte...
November 2016: Journal of Steroid Biochemistry and Molecular Biology
Bhagirath Chaurasia, Scott A Summers
In obesity and dyslipidemia, the oversupply of fat to tissues not suited for lipid storage induces cellular dysfunction that underlies diabetes and cardiovascular disease (i.e., lipotoxicity). Of the myriad lipids that accrue under these conditions, sphingolipids such as ceramide or its metabolites are amongst the most deleterious because they disrupt insulin sensitivity, pancreatic β cell function, vascular reactivity, and mitochondrial metabolism. Remarkably, inhibiting ceramide biosynthesis or catalyzing ceramide degradation in rodents ameliorates many metabolic disorders including diabetes, cardiomyopathy, insulin resistance, atherosclerosis, and steatohepatitis...
October 2015: Trends in Endocrinology and Metabolism: TEM
Ning Guo, Wenting Ai, Xin Jiang, Yanping Ren, Gang Tian, Xiaolin Xue
CD36 is a key transporter involved in fatty acid (FA) uptake and contributes to the accumulation of FA in cardiomyocytes. The objective of this study was to investigate the role of ouabain, a glycoside regulator of Na(+)/K(+)-ATPase, in the regulation of CD36 expression and FA accumulation. FATP1 transgenic (Tg) mice with lipotoxic cardiomyopathy displayed significantly increased cardiac CD36 expression and free fatty acid accumulation. The data on enzyme-linked immunosorbent assay showed that endogenous ouabain was decreased in the serum of Tg mice versus wild-type mice...
January 2016: Journal of Cardiovascular Pharmacology
J J Rayner, S Neubauer, O J Rider
Obesity is an independent risk factor for developing heart failure and the combination of the two disease states will prove to be a significant health burden over the coming years. Obesity is likely to contribute to the development of heart failure through a variety of mechanisms, including structural and functional changes, lipotoxicity and steatosis and altered substrate selection. However, once heart failure has developed, it seems that obesity confers a beneficial influence on prognosis in what has been termed the 'obesity paradox'...
August 2015: Obesity Reviews: An Official Journal of the International Association for the Study of Obesity
Xinzhu Wang, James A West, Andrew J Murray, Julian L Griffin
The ectopic deposition of fat is thought to lead to lipotoxicity and has been associated with mitochondrial dysfunction and diabetic cardiomyopathy. We have measured mitochondrial respiratory capacities in the hearts of ob/ob and wild-type mice on either a regular chow (RCD) or high-fat (HFD) diet across four age groups to investigate the impact of diet and age on mitochondrial function alongside a comprehensive strategy for metabolic profiling of the tissue. Myocardial mitochondrial dysfunction was only evident in ob/ob mice on RCD at 14 months, but it was detectable at 3 months on the HFD...
July 2, 2015: Journal of Proteome Research
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