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Lipotoxic cardiomyopathy

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https://www.readbyqxmd.com/read/27871808/new-mechanism-of-lipotoxicity-in-diabetic-cardiomyopathy-deficiency-of-endogenous-h2s-production-and-er-stress
#1
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
https://www.readbyqxmd.com/read/27728904/hypothalamic-lipids-key-regulators-of-whole-body-energy-balance
#2
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 (FAS) and AMP-activated protein kinase (AMPK), impacts both feeding and energy expenditure. However, lipids can also cause pathological alterations in the hypothalamus. Lipotoxicity is promoted by excess lipids in tissues non 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...
October 11, 2016: Neuroendocrinology
https://www.readbyqxmd.com/read/27606935/puerarin-suppresses-na-k-atpase-mediated-systemic-inflammation-and-cd36-expression-and-alleviates-cardiac-lipotoxicity-in-vitro-and-in-vivo
#3
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
https://www.readbyqxmd.com/read/27558317/fatty-old-hearts-role-of-cardiac-lipotoxicity-in-age-related-cardiomyopathy
#4
REVIEW
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
https://www.readbyqxmd.com/read/27523632/disruption-of-calpain-reduces-lipotoxicity-induced-cardiac-injury-by-preventing-endoplasmic-reticulum-stress
#5
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
https://www.readbyqxmd.com/read/27247947/physiological-and-pharmacological-roles-of-fgf21-in-cardiovascular-diseases
#6
REVIEW
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
https://www.readbyqxmd.com/read/26924249/lipid-metabolism-and-signaling-in-cardiac-lipotoxicity
#7
REVIEW
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
https://www.readbyqxmd.com/read/26921179/sodium-orthovanadate-suppresses-palmitate-induced-cardiomyocyte-apoptosis-by-regulation-of-the-jak2-stat3-signaling-pathway
#8
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
https://www.readbyqxmd.com/read/26899197/lipotoxicity-in-obesity-and-diabetes-related-cardiac-dysfunction
#9
REVIEW
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
https://www.readbyqxmd.com/read/26546819/impaired-fatty-acid-oxidation-as-a-cause-for-lipotoxicity-in-cardiomyocytes
#10
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
https://www.readbyqxmd.com/read/26429397/amplification-of-lipotoxic-cardiomyopathy-in-the-vdr-gene-knockout-mouse
#11
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 acyl transferase 1 (DGAT1), selectively in the cardiac myocyte...
September 28, 2015: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/26412155/ceramides-lipotoxic-inducers-of-metabolic-disorders
#12
REVIEW
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
https://www.readbyqxmd.com/read/26322921/low-dose-exogenous-ouabain-alleviates-cardiac-lipotoxicity-through-suppressing-expression-of-cd36
#13
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
https://www.readbyqxmd.com/read/26096833/the-paradox-of-obesity-cardiomyopathy-and-the-potential-for-weight-loss-as-a-therapy
#14
REVIEW
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
https://www.readbyqxmd.com/read/25985803/comprehensive-metabolic-profiling-of-age-related-mitochondrial-dysfunction-in-the-high-fat-fed-ob-ob-mouse-heart
#15
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
https://www.readbyqxmd.com/read/25888006/clinical-diabetic-cardiomyopathy-a-two-faced-disease-with-restrictive-and-dilated-phenotypes
#16
REVIEW
Petar M Seferović, Walter J Paulus
Diabetes mellitus-related cardiomyopathy (DMCMP) was originally described as a dilated phenotype with eccentric left ventricular (LV) remodelling and systolic LV dysfunction. Recently however, clinical studies on DMCMP mainly describe a restrictive phenotype with concentric LV remodelling and diastolic LV dysfunction. Both phenotypes are not successive stages of DMCMP but evolve independently to respectively heart failure with preserved left ventricular ejection fraction (HFPEF) or reduced left ventricular ejection fraction (HFREF)...
July 14, 2015: European Heart Journal
https://www.readbyqxmd.com/read/25808033/myocardial-metabolism-in-diabetic-cardiomyopathy-potential-therapeutic-targets
#17
REVIEW
Miranda M Sung, Shereen M Hamza, Jason R B Dyck
SIGNIFICANCE: Cardiovascular complications in diabetes are particularly serious and represent the primary cause of morbidity and mortality in diabetic patients. Despite early observations of cardiac dysfunction in diabetic humans, cardiomyopathy unique to diabetes has only recently been recognized. RECENT ADVANCES: Research has focused on understanding the pathogenic mechanisms underlying the initiation and development of diabetic cardiomyopathy. Emerging data highlight the importance of altered mitochondrial function as a major contributor to cardiac dysfunction in diabetes...
June 10, 2015: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/25753422/pgc-1-spargel-counteracts-high-fat-diet-induced-obesity-and-cardiac-lipotoxicity-downstream-of-tor-and-brummer-atgl-lipase
#18
Soda Balla Diop, Jumana Bisharat-Kernizan, Ryan Tyge Birse, Sean Oldham, Karen Ocorr, Rolf Bodmer
Obesity and metabolic syndrome are associated with an increased risk for lipotoxic cardiomyopathy, which is strongly correlated with excessive accumulation of lipids in the heart. Obesity- and type-2-diabetes-related disorders have been linked to altered expression of the transcriptional cofactor PGC-1α, which regulates the expression of genes involved in energy metabolism. Using Drosophila, we identify PGC-1/spargel (PGC-1/srl) as a key antagonist of high-fat diet (HFD)-induced lipotoxic cardiomyopathy...
March 4, 2015: Cell Reports
https://www.readbyqxmd.com/read/25645463/implications-of-ghrelin-and-hexarelin-in-diabetes-and-diabetes-associated-heart-diseases
#19
REVIEW
Rasha Mofeed Habeeb Mosa, Zhen Zhang, Renfu Shao, Chao Deng, Jiezhong Chen, Chen Chen
Ghrelin and its synthetic analog hexarelin are specific ligands of growth hormone secretagogue (GHS) receptor. GHS have strong growth hormone-releasing effect and other neuroendocrine activities such as stimulatory effects on prolactin and adrenocorticotropic hormone secretion. Recently, several studies have reported other beneficial functions of GHS that are independent of GH. Ghrelin and hexarelin, for examples, have been shown to exert GH-independent cardiovascular activity. Hexarelin has been reported to regulate peroxisome proliferator-activated receptor gamma (PPAR-γ) in macrophages and adipocytes...
June 2015: Endocrine
https://www.readbyqxmd.com/read/25499591/astragalus-polysaccharides-repress-myocardial-lipotoxicity-in-a-pparalpha-dependent-manner-in-vitro-and-in-vivo-in-mice
#20
Wei Chen, Yanni Lai, Liying Wang, Yanping Xia, Wenjie Chen, Xuelan Zhao, Maohua Yu, Yiming Li, Yu Zhang, Hongying Ye
BACKGROUND: The role of peroxisome proliferator-activated receptor alpha (PPARα) in the development of myocardial lipotoxicity is widely observed in diabetic disorders. Thus, we investigated if treatment of Astragalus polysaccharides modulates lipotoxic cardiomyopathy both in vivo and in vitro through PPARα mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: The effects of Astragalus polysaccharides (APS) on PPARα target gene expression and protein levels were tested in vitro and in vivo, including in mice with PPARα cardiac-restricted overexpression [myosin heavy chain (MHC)-PPARα] and in H9c2 embryonic rat cardiomyocytes with or without PPARα agonist...
March 2015: Journal of Diabetes and its Complications
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