Lipoprotein Secretion and Triglyceride Stores in the Heart

Björkegren, Johan; Véniant, Murielle M.; Kim, Sun K.; Withycombe, Shannon K.; Wood, Philip A.; Hellerstein, Marc K.; Neese, Richard A.; Young, Stephen G.

doi:10.1074/jbc.m106839200

Cited by 80 publications

(65 citation statements)

References 40 publications

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“…Because HuB/hLpL GPI hearts secrete more apoB, it is likely that this transgene increased lipid removal from the heart. This conclusion is supported by studies that showed a reduction in heart lipid due to apoB expression in long chain acyl CoA dehydrogenase knockout mice (10). In addition, these investigators found that cardiacspecific loss of microsomal triglyceride transfer protein, leading to an inability to produce lipoproteins in the heart, increased cardiac triglyceride stores.…”

Section: Discussionsupporting

confidence: 73%

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Apolipoprotein B Production Reduces Lipotoxic Cardiomyopathy

Yokoyama

Yagyu

et al. 2004

Journal of Biological Chemistry

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Lipid accumulation is associated with cardiac dysfunction in diabetes and obesity. Transgenic mice expressing non-transferable lipoprotein lipase (LpL) with a glycosylated phosphatidyl-inositol (GPI) anchor in cardiomyocytes have dilated cardiomyopathy. However, the mechanisms responsible for lipid accumulation and cardiomyopathy are not clear. Hearts from 3-month-old mice expressing GPI-anchored human LpL (hLpL GPI ) mice had increased fatty acid oxidation and heart failure genes and decreased glucose transporter genes. 6-month-old mice had increased mRNA expression and activation of the apoptosis marker caspase-3. Moreover, hLpL GPI hearts had significant cytochrome c release from mitochondria to cytosol. Low density lipoprotein uptake was greater in hLpL GPI hearts, and this was associated with more intracellular apolipoprotein B (apoB). To test whether lipid accumulation in the hLpL GPI heart is reduced by cardiac expression of apoB, hLpL GPI mice were bred with transgenic human apoB (HuB)-expressing mice. Hearts of HuB/hLpL GPI mice had less triglyceride (38%) and free fatty acids (19%), secreted more apoB, and expressed less atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) and more glucose transporter 4 (GLUT4). The increased mortality of the mice was abrogated by the transgenic expression of apoB. Therefore, we hypothesize that cardiac apoB expression improves cardiomyopathy by increasing lipid resecretion from the heart.

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Section: Discussionsupporting

confidence: 73%

“…Hearts synthesized and secreted lipoproteins (8). Cardiac apoB expression led to reduced heart lipids after induction of diabetes in mice (9) and in the presence of long chain acyl coA dehydrogenase deficiency (10). This supported the hypothesis that heart apoB enables the heart to secrete excess lipid in lipoproteins (8).…”

supporting

confidence: 67%

Apolipoprotein B Production Reduces Lipotoxic Cardiomyopathy

Yokoyama

Yagyu

et al. 2004

Journal of Biological Chemistry

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“…In contrast, 3 H oleate specific activity was not different in coronary sinus and arterial plasma (P ϭ 0.17). There was a strong negative correlation between 14 C oleate fractional extraction (34 Ϯ 5%) and plasma oleate concentration (R ϭ 0.973, P Ͻ 0.01, data not shown).…”

Section: Resultsmentioning

confidence: 90%

“…Coronary sinus concentrations of both oleate and total FFA were significantly lower than arterial (P Ͻ 0.001). Coronary sinus 14 C oleate specific activities were also lower than arterial (P ϭ 0.033). In contrast, 3 H oleate specific activity was not different in coronary sinus and arterial plasma (P ϭ 0.17).…”

Section: Resultsmentioning

confidence: 94%

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Myocardial Uptake of Circulating Triglycerides in Nondiabetic Patients With Heart Disease

et al. 2007

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Animal studies indicate that oversupply of fatty acids derived from the action of cardiac lipoprotein lipase (LPL) on plasma lipoproteins may contribute to myocardial dysfunction. However, the contribution of circulating triglycerides to myocardial fatty acid supply in humans is not known. Six postabsorptive nondiabetic subjects who were scheduled for diagnostic coronary angiography were studied. 14 C oleate and a lipid emulsion labeled with 3 H triolein were infused to assess myocardial uptake of free fatty acids (FFAs) and triglycerides, as well as myocardial spillover of LPL-generated fatty acids. Six paired blood samples were taken from the femoral artery and the coronary sinus. Coronary sinus concentrations of unlabeled triglycerides were slightly, but not significantly, lower than arterial (P ‫؍‬ 0.12), whereas labeled triglyceride concentrations were significantly lower in the coronary sinus than in the artery (P < 0.05; extraction fraction Х11%). Triglycerides and FFAs accounted for ϳ17% and ϳ83%, respectively, of myocardial fatty acid uptake. Systemic and myocardial fractional spillover of LPL-generated fatty acids was 49.0 ؎ 7% and 34.7 ؎ 13%, respectively. The myocardium was a minor contributor to systemic triglyceride uptake (ϳ3%) and a trivial contributor to systemic FFA production (ϳ0.5%). These results indicate that circulating triglycerides may be a significant source of fatty acids for myocardial respiration. Diabetes 56:527-530, 2007 I t has been suggested that free fatty acids (FFAs) are the primary energy source for the myocardium (1). However, the heart contains a considerable amount of lipoprotein lipase (LPL) (2), and studies in animals have found significant triglyceride uptake by the myocardium. It has been suggested recently that circulating triglycerides are actually the primary lipid fuel for this tissue (3). Very little information on the role of triglycerides in human myocardial metabolism is available, however. The present study was therefore undertaken to determine whether significant uptake of triglycerides occurs in the heart and also to determine the relative role of triglycerides and FFAs in the provision of lipid fuel to that tissue. RESEARCH DESIGN AND METHODSInformed written consent was obtained from six Caucasian subjects (three male, three female; average age 65 years, weight 91.3 kg, BMI 30.9 kg/m 2 ) scheduled for diagnostic coronary angiography. Individuals with diabetes, significant hypertriglyceridemia (Ͼ2.26 mmol/l), congestive heart failure, unstable angina, recent stroke, previous myocardial infarction or angioplasty, left ventricular ejection fraction Ͻ45%, or significant endocrine, hepatic, or renal disorders were excluded. Five of the six subjects proved to have coronary artery disease; four of these underwent percutaneous stent placement. One subject had valve replacement surgery for aortic stenosis.Subjects were studied according to a protocol approved by the Mayo Institutional Review Board. On the morning of the study (after an overnight fast and after ob...

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Green tea polyphenols improve cardiac muscle mRNA and protein levels of signal pathways related to insulin and lipid metabolism and inflammation in insulin‐resistant rats

Qin

Polansky

Dawson

et al. 2010

Molecular Nutrition Food Res

100

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Epidemiological studies indicate that the consumption of green tea polyphenols (GTP) may reduce the risk of coronary artery disease. To explore the underlying mechanisms of action at the molecular level, we examined the effects of GTP on the cardiac mRNA and protein levels of genes involved in insulin and lipid metabolism and inflammation. In rats fed a high-fructose diet, supplementation with GTP (200 mg/kg BW daily dissolved in distilled water) for 6 wk, reduced systemic blood glucose, plasma insulin, retinol-binding protein 4, soluble CD36, cholesterol, triglycerides, free fatty acids and LDL-C levels, as well as the pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and IL-6. GTP did not affect food intake, bodyweight and heart weight. In the myocardium, GTP also increased the insulin receptor (Ir), insulin receptor substrate 1 and 2 (Irs1 and Irs2), phosphoinositide-3-kinase (Pi3k), v-akt murine thymoma viral oncogene homolog 1 (Akt1), glucose transporter 1 and 4 (Glut1 and Glut4) and glycogen synthase 1 (Gys1) expression but inhibited phosphatase and tensin homolog deleted on chromosome ten (Pten) expression and decreased glycogen synthase kinase 3beta (Gsk3beta) mRNA expression. The sterol regulatory element-binding protein-1c (Srebp1c) mRNA, microsomal triglyceride transfer protein (Mttp) mRNA and protein, Cd36 mRNA and cluster of differentiation 36 protein levels were decreased and peroxisome proliferator-activated receptor (Ppar)gamma mRNA levels were increased. GTP also decreased the inflammatory factors: Tnf, Il1b and Il6 mRNA levels, and enhanced the anti-inflammatory protein, zinc-finger protein, protein and mRNA expression. In summary, consumption of GTP ameliorated the detrimental effects of high-fructose diet on insulin signaling, lipid metabolism and inflammation in the cardiac muscle of rats.

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Lipoprotein Secretion and Triglyceride Stores in the Heart

Cited by 80 publications

References 40 publications

Apolipoprotein B Production Reduces Lipotoxic Cardiomyopathy

Apolipoprotein B Production Reduces Lipotoxic Cardiomyopathy

Myocardial Uptake of Circulating Triglycerides in Nondiabetic Patients With Heart Disease

Green tea polyphenols improve cardiac muscle mRNA and protein levels of signal pathways related to insulin and lipid metabolism and inflammation in insulin‐resistant rats

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