The Experts below are selected from a list of 216 Experts worldwide ranked by ideXlab platform
Lars Nielsen - One of the best experts on this subject based on the ideXlab platform.
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Cardiac Expression of Microsomal Triglyceride Transfer Protein Is Increased in Obesity and Serves to Attenuate Cardiac Triglyceride Accumulation
PloS one, 2009Co-Authors: Emil D. Bartels, Jan Møller Nielsen, Lars Hellgren, Thorkil Ploug, Lars NielsenAbstract:Obesity causes lipid accumulation in the heart and may lead to lipotoxic heart disease. Traditionally, the size of the cardiac Triglyceride pool is thought to reflect the balance between uptake and β-oxidation of fatty acids. However, Triglycerides can also be exported from cardiomyocytes via secretion of apolipoproteinB-containing (apoB) lipoproteins. Lipoprotein formation depends on expression of microsomal Triglyceride transfer protein (MTP); the mouse expresses two isoforms of MTP, A and B. Since many aspects of the link between obesity-induced cardiac disease and cardiac lipid metabolism remain unknown, we investigated how cardiac lipoprotein synthesis affects cardiac expression of Triglyceride metabolism-controlling genes, insulin sensitivity, and function in obese mice. Heart-specific ablation of MTP-A in mice using Cre-loxP technology impaired upregulation of MTP expression in response to increased fatty acid availability during fasting and fat feeding. This resulted in cardiac Triglyceride accumulation but unaffected cardiac insulin-stimulated glucose uptake. Long-term fat-feeding of male C57Bl/6 mice increased cardiac Triglycerides, induced cardiac expression of Triglyceride metabolism-controlling genes and attenuated heart function. Abolishing cardiac Triglyceride accumulation in fat-fed mice by overexpression of an apoB transgene in the heart prevented the induction of Triglyceride metabolism-controlling genes and improved heart function. The results suggest that in obesity, the physiological increase of cardiac MTP expression serves to attenuate cardiac Triglyceride accumulation albeit without major effects on cardiac insulin sensitivity. Nevertheless, the data suggest that genetically increased lipoprotein secretion prevents development of obesity-induced lipotoxic heart disease.
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Microsomal Triglyceride Transfer Protein Gene Expression and Triglyceride Accumulation in Hypoxic Human Hearts
Arteriosclerosis thrombosis and vascular biology, 2002Co-Authors: Lars Nielsen, Mario J. Perko, Henrik Arendrup, Claus B. AndersenAbstract:Objectives— Cardiac myocytes secrete apolipoprotein (apo)B-containing lipoproteins. Their function may be the removal of Triglycerides when β-oxidation of fatty acids is decreased, eg, during hypoxia. To test this hypothesis, we examined heart biopsies from patients undergoing coronary artery bypass graft (CABG, n=13) or valve replacement (n=6) surgery. Methods and Results— Ventricular microsomal Triglyceride transfer protein ( P =0.02) and apoB ( P =0.04) mRNA levels were both ≈2-fold higher in CABG compared with valve replacement patients. In CABG patients, ventricular microsomal Triglyceride transfer protein mRNA levels were negatively associated with the Triglyceride content in ventricular myocytes ( r =−0.70; P =0.02) and with mRNA levels of sterol regulatory element binding protein-1 ( r =−0.74; P =0.004). Conclusions— The results are compatible with the notion that cardiac lipoprotein production is increased in hypoxic human ventricle, possibly as a result of decreased sterol regulatory element binding protein-1 expression. This might attenuate accumulation of Triglycerides in cardiac myocytes.
Peter Arner - One of the best experts on this subject based on the ideXlab platform.
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Adipocyte Triglyceride turnover is independently associated with atherogenic dyslipidemia.
Journal of the American Heart Association, 2012Co-Authors: Keith Frayn, Samuel Bernard, Kirsty Spalding, Peter ArnerAbstract:BACKGROUND: Inappropriate storage of fatty acids as Triglycerides in adipocytes and their removal from adipocytes through lipolysis and subsequent oxidation may cause the atherogenic dyslipidemia phenotype of elevated apolipoprotein B levels and subsequent hyperTriglyceridemia. We tested whether turnover of Triglycerides in fat cells was related to dyslipidemia. METHODS AND RESULTS: The age of Triglycerides (reflecting removal) and Triglyceride storage in adipocytes was determined under free living conditions by measuring incorporation of atmospheric (14)C into these lipids within the adipocytes in 47 women and 26 men with a large interindividual variability in body mass index. Because limited (14)C data were available, Triglyceride age was also determined in 97 men and 233 women by using an algorithm based on adipocyte lipolysis, body fat content, waist-to-hip ratio, and insulin sensitivity. This cohort consisted of nonobese subjects since obesity per se is related to all components in the algorithm. Triglyceride turnover (age and storage) was compared with plasma levels of apolipoproteins and lipids. Plasma levels of apolipoprotein B and Triglycerides were positively related to Triglyceride age in adipocytes, when measured directly using radiocarbon analyses (r=0.45 to 0.47; P
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Dynamics of human adipose lipid turnover in health and metabolic disease.
Nature, 2011Co-Authors: Peter Arner, Samuel Bernard, Mehran Salehpour, Göran Possnert, Jakob Liebl, Peter Steier, Bruce A Buchholz, Mats Eriksson, Erik Arner, Hans HaunerAbstract:Adipose tissue mass is determined by the storage and removal of Triglycerides in adipocytes. Little is known, however, about adipose lipid turnover in humans in health and pathology. To study this in vivo, here we determined lipid age by measuring (14)C derived from above ground nuclear bomb tests in adipocyte lipids. We report that during the average ten-year lifespan of human adipocytes, Triglycerides are renewed six times. Lipid age is independent of adipocyte size, is very stable across a wide range of adult ages and does not differ between genders. Adipocyte lipid turnover, however, is strongly related to conditions with disturbed lipid metabolism. In obesity, Triglyceride removal rate (lipolysis followed by oxidation) is decreased and the amount of Triglycerides stored each year is increased. In contrast, both lipid removal and storage rates are decreased in non-obese patients diagnosed with the most common hereditary form of dyslipidaemia, familial combined hyperlipidaemia. Lipid removal rate is positively correlated with the capacity of adipocytes to break down Triglycerides, as assessed through lipolysis, and is inversely related to insulin resistance. Our data support a mechanism in which adipocyte lipid storage and removal have different roles in health and pathology. High storage but low Triglyceride removal promotes fat tissue accumulation and obesity. Reduction of both Triglyceride storage and removal decreases lipid shunting through adipose tissue and thus promotes dyslipidaemia. We identify adipocyte lipid turnover as a novel target for prevention and treatment of metabolic disease.
Goro Matsumiya - One of the best experts on this subject based on the ideXlab platform.
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Triglyceride Deposit Cardiomyovasculopathy
The New England journal of medicine, 2008Co-Authors: Ken-ichi Hirano, Yasuhiko Sakata, Yoshihiko Ikeda, Nobuhiro Zaima, Goro MatsumiyaAbstract:Triglyceride deposit cardiomyovasculopathy (TGCV) is a novel disease concept we found in Japanese cardiac transplant candidates in 2008. Probands carried mutations in the PNPLA2 gene encoding adipose Triglyceride lipase (ATGL). ATGL is the major enzyme that catalyzes the initial rate-limiting step of intracellular Triglyceride hydrolysis to release free nonesterified long-chain fatty acids (LCFAs), which is an essential energy source for the normal heart. Patients with TGCV show ectopic accumulation of Triglycerides in cardiomyocytes and smooth muscle cells resulting from abnormal intracellular metabolism of Triglycerides and LCFA. TGCV is classified into primary and idiopathic TGCV with and without genetic ATGL deficiency, respectively. Both types of TGCV patients suffer from severe heart failure, arrhythmia, and coronary artery disease caused by lipotoxicity and energy failure at cellular levels. The Japan TGCV study group provided the diagnostic guideline and has been trying to develop a nutritional therapeutics with medium-chain fatty acids in order to overcome this intractable disease one day earlier. In this chapter, we describe clinical signs and symptoms, laboratory findings, diagnosis, and possible therapies of TGCV.
Ken-ichi Hirano - One of the best experts on this subject based on the ideXlab platform.
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Triglyceride deposit cardiomyovasculopathy
Nihon rinsho. Japanese journal of clinical medicine, 2013Co-Authors: Ken-ichi HiranoAbstract:Cholesterol is a vital causal factor and focus of research into heart diseases, however the involvement of Triglycerides remains unclear. We recently reported a patient suffering from severe congestive heart failure and needing cardiac transplantation. Massive accumulation of Triglycerides was noted in coronary atherosclerotic lesions as well as in the myocardium. We named this phenotype"Triglyceride deposit cardiomyovasculopathy (TGCV)". The patient was identified as homozygous for a genetic mutation in the adipose Triglyceride lipase (ATGL), an essential molecule for hydrolysis of intracellular Triglycerides. In this paper, we describe clinical characteristics of ATGL deficiency and discuss what we can learn from this disorder.
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Triglyceride Deposit Cardiomyovasculopathy
The New England journal of medicine, 2008Co-Authors: Ken-ichi Hirano, Yasuhiko Sakata, Yoshihiko Ikeda, Nobuhiro Zaima, Goro MatsumiyaAbstract:Triglyceride deposit cardiomyovasculopathy (TGCV) is a novel disease concept we found in Japanese cardiac transplant candidates in 2008. Probands carried mutations in the PNPLA2 gene encoding adipose Triglyceride lipase (ATGL). ATGL is the major enzyme that catalyzes the initial rate-limiting step of intracellular Triglyceride hydrolysis to release free nonesterified long-chain fatty acids (LCFAs), which is an essential energy source for the normal heart. Patients with TGCV show ectopic accumulation of Triglycerides in cardiomyocytes and smooth muscle cells resulting from abnormal intracellular metabolism of Triglycerides and LCFA. TGCV is classified into primary and idiopathic TGCV with and without genetic ATGL deficiency, respectively. Both types of TGCV patients suffer from severe heart failure, arrhythmia, and coronary artery disease caused by lipotoxicity and energy failure at cellular levels. The Japan TGCV study group provided the diagnostic guideline and has been trying to develop a nutritional therapeutics with medium-chain fatty acids in order to overcome this intractable disease one day earlier. In this chapter, we describe clinical signs and symptoms, laboratory findings, diagnosis, and possible therapies of TGCV.
Karol E. Watson - One of the best experts on this subject based on the ideXlab platform.
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Triglycerides: A reappraisal
Trends in cardiovascular medicine, 2017Co-Authors: Philipp Wiesner, Karol E. WatsonAbstract:Elevated cholesterol levels are clearly independently associated with adverse cardiovascular events. Another class of lipid particles, Triglycerides, is also abundant in the human body and has been found in atherosclerotic plaques. Recent observational studies have demonstrated an association between elevated Triglyceride levels and increased risk for future cardiovascular events. With this knowledge and the discovery of effective agents to lower Triglyceride levels, the management of Triglycerides is currently undergoing a renaissance. Unfortunately, no randomized, controlled clinical trials have been completed to date, proving that lowering Triglycerides will reduce cardiovascular events. In this review we highlight some of the evidence that led to this stage and discuss the current data on pharmacologic intervention of Triglyceride levels and the effect on clinical outcomes. Lastly, we want to give the reader insight on what the most recent lipid guidelines state about clinical Triglyceride management, mention new pharmacological agents, and highlight the clinical evidence for safe and effective lowering of Triglycerides levels with life style modification.
