Myocardial substrate utilization in perfused hearts isolated from adrenalectomizedcats

1975 ◽  
Vol 228 (6) ◽  
pp. 1656-1662 ◽  
Author(s):  
AC Beardsley ◽  
AM Lefer
Keyword(s):  
Fatty Acid ◽  
Constant Pressure ◽  
Fatty Acid Uptake ◽  
Fatty Acid Transport ◽  
Acid Uptake ◽  
Constant Flow ◽  
Isolated Hearts ◽  
Myocardial Substrate ◽  
Perfused Hearts ◽  
Krebs Henseleit Buffer

Isolated hearts form chronically adrenalectomized cats were perfused with Krebs-Henseleit buffer plus either glucose (10mM) or palmitate (0.4 mM) under various conditions of constant pressure and constant flow. Glucose uptake in adrenalectomizedhearts was not diminished from control values under conditions of constant pressure, constant flow, anoxia, or insulin stimulation. Palmatic acid uptake and oxygen consumption were significantly reduced (P less than 0.02) in adrenalectomized hearts. This diminished fatty acid utilization was also reflected in a significantly lower CO'2 production and incorporation of the palmitate into myocardial triglycerides. The decreased fatty acid uptake by adrenalectomized cat hearts may represent aserious defect in myocardial metabolism since lipids are the major energy substrate forthe heart. Whether the defect occurs in fatty acid transport or activation cannot beelucidated by this study. However, it is unlikely that this defect has a major contributory effect on the dysfunction of adrenalectomized hearts since the myocardium iscabable of using other energy substrates readily.

scholarly journals Lipid Accumulation and Chronic Kidney Disease

Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 722 ◽  
Author(s):  
Zhibo Gai ◽  
Tianqi Wang ◽  
Michele Visentin ◽  
Gerd Kullak-Ublick ◽  
Xianjun Fu ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Kidney Disease ◽  
Lipid Accumulation ◽  
Scavenger Receptor ◽  
Fatty Acid Uptake ◽  
Lipid Lowering ◽  
Fatty Acid Transport ◽  
Acid Uptake

Obesity and hyperlipidemia are the most prevalent independent risk factors of chronic kidney disease (CKD), suggesting that lipid accumulation in the renal parenchyma is detrimental to renal function. Non-esterified fatty acids (also known as free fatty acids, FFA) are especially harmful to the kidneys. A concerted, increased FFA uptake due to high fat diets, overexpression of fatty acid uptake systems such as the CD36 scavenger receptor and the fatty acid transport proteins, and a reduced β-oxidation rate underlie the intracellular lipid accumulation in non-adipose tissues. FFAs in excess can damage podocytes, proximal tubular epithelial cells and the tubulointerstitial tissue through various mechanisms, in particular by boosting the production of reactive oxygen species (ROS) and lipid peroxidation, promoting mitochondrial damage and tissue inflammation, which result in glomerular and tubular lesions. Not all lipids are bad for the kidneys: polyunsaturated fatty acids (PUFA) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) seem to help lag the progression of chronic kidney disease (CKD). Lifestyle interventions, especially dietary adjustments, and lipid-lowering drugs can contribute to improve the clinical outcome of patients with CKD.

scholarly journals The effect of high glucose on lipid metabolism in the human placenta

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Charlotte H. Hulme ◽  
Anna Nicolaou ◽  
Sharon A. Murphy ◽  
Alexander E. P. Heazell ◽  
Jenny E. Myers ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
High Glucose ◽  
Fatty Acid Uptake ◽  
Fatty Acid Transport ◽  
Acid Uptake ◽  
Obese Women ◽  
Lipid Transfer ◽  
Glucose Levels ◽  
Fatty Acid Transport Proteins

Abstract Diabetes mellitus (DM) during pregnancy can result in fetal overgrowth, likely due to placental dysfunction, which has health consequences for the infant. Here we test our prediction from previous work using a placental cell line that high glucose concentrations affect placental lipid metabolism. Placentas from women with type 1 (n = 13), type 2 (n = 6) or gestational (n = 12) DM, BMI-matched to mothers without DM (n = 18), were analysed for lipase and fatty acid transport proteins and fatty acid and triglyceride content. Explants from uncomplicated pregnancies (n = 6) cultured in physiological or high glucose were similarly analysed. High glucose levels did not alter placental lipase or transporter expression or the profile and abundance of fatty acids, but triglyceride levels were higher (p < 0.05), suggesting reduced β- oxidation. DM did not affect placental protein expression or fatty acid profile. Triglyceride levels of placentas from mothers with pre-existing DM were similar to controls, but higher in obese women with gestational DM. Maternal hyperglycemia may not affect placental fatty acid uptake and transport. However, placental β-oxidation is affected by high glucose and reduced in a subset of women with DM. Abnormal placental lipid metabolism could contribute to increased maternal-fetal lipid transfer and excess fetal growth in some DM pregnancies.

Effect of surface and intracellular pH on hepatocellular fatty acid uptake

1996 ◽  
Vol 271 (6) ◽  
pp. G1067-G1073
Author(s):  
C. Elsing ◽  
A. Kassner ◽  
W. Stremmel
Keyword(s):  
Fatty Acids ◽  
Plasma Membrane ◽  
Fatty Acid ◽  
Intracellular Ph ◽  
Outer Surface ◽  
Fatty Acid Uptake ◽  
Proton Gradient ◽  
Fatty Acid Transport ◽  
Acid Uptake ◽  
Acid Transport

Fatty acids enter hepatocytes, at least in part, by a carrier-mediated uptake mechanism. The importance of driving forces for fatty acid uptake is still controversial. To evaluate possible driving mechanisms for fatty acid transport across plasma membranes, we examined the role of transmembrane proton gradients on fatty acid influx in primary cultured rat hepatocytes. After hepatocytes were loaded with SNARF-1 acetoxymethyl ester, changes in intracellular pH (pHi) under different experimental conditions were measured and recorded by confocal laser scanning microscopy. Fatty acid transport was increased by 45% during cellular alkalosis, achieved by adding 20 mM NH4Cl to the medium, and a concomitant paracellular acidification was observed. Fatty acid uptake was decreased by 30% during cellular acidosis after withdrawal of NH4Cl from the medium. Cellular acidosis activates the Na+/H+ antiporter to export excessive protons to the outer cell surface. Inhibition of Na+/H+ antiporter activity by amiloride diminishes pHi recovery and thereby accumulation of protons at the outer surface of the plasma membrane. Under these conditions, fatty acid uptake was further inhibited by 57% of control conditions. This suggests stimulation of fatty acid influx by an inwardly directed proton gradient. The accelerating effect of protons at the outer surface of the plasma membrane was confirmed by studies in which pH of the medium was varied at constant pHi. Significantly higher fatty acid influx rates were observed at low buffer pH. Recorded differences in fatty acid uptake appeared to be independent of changes in membrane potential, because BaCl2 did not influence initial uptake velocity during cellular alkalosis and paracellular acidosis. Moreover, addition of oleate-albumin mixtures to the NH4Cl incubation buffer did not change the observed intracellular alkalinization. In contrast, after cells were acid loaded, addition of oleate-albumin solutions to the recovery buffer increased pHi recovery rates from 0.21 +/- 0.02 to 0.36 +/- 0.05 pH units/min (P < 0.05), indicating that fatty acids further stimulate Na+/H+ antiporter activity during pHi recovery from an acid load. It is concluded that carrier-mediated uptake of fatty acids in hepatocytes follows an inwardly directed transmembrane proton gradient and is stimulated by the presence of H+ at the outer surface of the plasma membrane.

Protein-Mediated Fatty Acid Uptake: Novel Insights from In Vivo Models

Physiology ◽  
2006 ◽  
Vol 21 (4) ◽  
pp. 259-268 ◽  
Author(s):  
Holger Doege ◽  
Andreas Stahl
Keyword(s):  
Fatty Acid ◽  
Energy Homeostasis ◽  
Fatty Acid Uptake ◽  
Cellular Fatty Acid ◽  
Fatty Acid Transport ◽  
Acid Uptake ◽  
In Vivo Models ◽  
Knockout Animal ◽  
Fatty Acid Transport Proteins

Long-chain fatty acids are both important metabolites as well as signaling molecules. Fatty acid transport proteins are key mediators of cellular fatty acid uptake and recent transgenic and knockout animal models have provided new insights into their contribution to energy homeostasis and to pathological processes, including obesity and insulin desensitization.

Fatty Acid Transport Proteins Facilitate Fatty Acid Uptake in Skeletal Muscle

2000 ◽  
Vol 25 (5) ◽  
pp. 353-412 ◽  
Author(s):  
Joost J.F.P. Luiken ◽  
Jan F.C. Glatz ◽  
Arend Bonen
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Uptake ◽  
Oxidative Capacity ◽  
Transport Proteins ◽  
Fatty Acid Transport ◽  
Acid Uptake ◽  
Giant Vesicles ◽  
Cellular Processes ◽  
Metabolic Role ◽  
Fatty Acid Transport Proteins

In view of the importance of long chain fatty acids (LCFAs) to many cellular processes, it may be desirable to regulate the LCFA disposition in the cell. Such regulation may be present at the level of the plasma membrane, since a number of putative LCFA transport proteins have been cloned. The development of a model system of giant vesicles has proven to be important in identifying the metabolic role of the LCFA transport system. LCFA transport rates and transporters (FABPpm and FAT/CD36) are scaled with oxidative capacity of heart and muscle. FAT/CD36 is a critical LCFA transport protein in muscle. With chronic contraction the increase in this protein also results in an increase in LCFA transport. Most importantly, LCFA transport is also increased acutely by muscle contraction, involving the translocation of FAT/CD36 from intracellular depots to the surface of the muscle cell. The acute (minutes) and chronic (days) regulation of LCFA transporters and transport by muscle may be an important mechanism for LCFA utilization during exercise and adaptable with training and with a metabolic disease such as type 2 diabetes. Key words: FAT/CD36, FABPpm, giant vesicles, transport

scholarly journals Differences in ischemia-reperfusion-induced endothelial changes in hearts perfused at constant flow and constant pressure

2008 ◽  
Vol 105 (6) ◽  
pp. 1779-1787 ◽  
Author(s):  
Raja B. Singh ◽  
Vijayan Elimban ◽  
Naranjan S. Dhalla
Keyword(s):  
Cardiac Function ◽  
Constant Pressure ◽  
Contractile Activity ◽  
Ischemia Reperfusion ◽  
No Synthase ◽  
Constant Flow ◽  
Calpain Activity ◽  
Isolated Hearts ◽  
Rat Hearts ◽  
Perfused Hearts

Isolated hearts subjected to ischemia-reperfusion (I/R) exhibit depressed cardiac performance and alterations in subcellular function. Since hearts perfused at constant flow (CF) and constant pressure (CP) show differences in their contractile response to I/R, this study was undertaken to examine mechanisms responsible for these I/R-induced alterations in CF-perfused and CP-perfused hearts. Rat hearts, perfused at CF (10 ml/min) or CP (80 mmHg), were subjected to I/R (30 min global ischemia followed by 60 min reperfusion), and changes in cardiac function as well as sarcolemmal (SL) Na+-K+-ATPase activity, sarcoplasmic reticulum (SR) Ca2+ uptake, and endothelial function were monitored. The I/R-induced depressions in cardiac function, SL Na+-K+-ATPase, and SR Ca2+-uptake activities were greater in hearts perfused at CF than in hearts perfused at CP. In hearts perfused at CF, I/R-induced increase in calpain activity and decrease in nitric oxide (NO) synthase (endothelial NO synthase) protein content in the heart as well as decrease in NO concentration of the perfusate were greater than in hearts perfused at CP. These changes in contractile activity and biochemical parameters due to I/R in hearts perfused at CF were attenuated by treatment with l-arginine, a substrate for NO synthase, while those in hearts perfused at CP were augmented by treatment with NG-nitro-l-arginine methyl ester, an inhibitor of NO synthase. The results indicate that the I/R-induced differences in contractile responses and alterations in subcellular organelles between hearts perfused at CF and CP may partly be attributed to greater endothelial dysfunction in CF-perfused hearts than that in CP-perfused hearts.

Myocardial substrate uptake in lambs with and without aortopulmonary shunts during strenuous exercise

1993 ◽  
Vol 75 (2) ◽  
pp. 505-512
Author(s):  
J. W. Gratama ◽  
M. Dalinghaus ◽  
J. J. Meuzelaar ◽  
A. M. Gerding ◽  
J. H. Koers ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Free Fatty Acids ◽  
Fatty Acid Uptake ◽  
Acid Uptake ◽  
Substrate Uptake ◽  
O2 Consumption ◽  
Myocardial Substrate ◽  
Myocardial O2 Consumption ◽  
And Control

Increased myocardial fatty acid uptake during acute exercise could adversely affect myocardial O2 consumption in lambs with left-to-right shunts, which would be unfavorable in view of their decreased coronary blood flow reserve. Therefore, we studied myocardial substrate uptake (glucose, lactate, pyruvate, free fatty acids, triglycerides, beta-hydroxybutyrate, and acetoacetate) in 10 7-wk-old lambs with an aortopulmonary left-to-right shunt [61 +/- 3% (SE) of left ventricular output] and 9 control lambs during strenuous treadmill exercise. The hemodynamic reaction to exercise was similar in shunt and control lambs. The peripheral metabolic response to exercise was also similar in the two groups: glucose free fatty acids, and, most prominently, lactate concentrations increased. Myocardial O2 consumption increased but less in shunt than in control lambs because of a smaller increase in heart rate. In both groups myocardial lactate uptake increased substantially at the cost of other substrates, providing the heart with 40% of its oxidative metabolism. Fatty acid uptake was not different between the two groups. In conclusion, our data reveal no essential differences in myocardial substrate uptake between shunt and control lambs during a substantial circulatory load.

Insulin induces the translocation of the fatty acid transporter FAT/CD36 to the plasma membrane

2002 ◽  
Vol 282 (2) ◽  
pp. E491-E495 ◽  
Author(s):  
Joost J. F. P. Luiken ◽  
David J. Dyck ◽  
Xiao-Xia Han ◽  
Narendra N. Tandon ◽  
Yoga Arumugam ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Fatty Acid ◽  
Muscle Contraction ◽  
Kinase Inhibitor ◽  
Fatty Acid Uptake ◽  
Fatty Acid Transport ◽  
Acid Uptake ◽  
Hindlimb Muscles ◽  
Fatty Acid Transporter ◽  
Acid Transporter

It is well known that muscle contraction and insulin can independently translocate GLUT-4 from an intracellular depot to the plasma membrane. Recently, we have shown that the fatty acid transporter FAT/CD36 is translocated from an intracellular depot to the plasma membrane by muscle contraction (<30 min) (Bonen et al. J Biol Chem 275: 14501–14508, 2000). In the present study, we examined whether insulin also induced the translocation of FAT/CD36 in rat skeletal muscle. In studies in perfused rat hindlimb muscles, we observed that insulin increased fatty acid uptake by +51%. Insulin increased the rate of palmitate incorporation into triacylglycerols, diacylglycerols, and phospholipids ( P < 0.05) while reducing muscle palmitate oxidation ( P < 0.05). Perfusing rat hindlimb muscles with insulin increased plasma membrane FAT/CD36 by +48% ( P < 0.05), whereas concomitantly the intracellular FAT/CD36 depot was reduced by 68% ( P < 0.05). These insulin-induced effects on FAT/CD36 translocation were inhibited by the phosphatidylinositol 3-kinase inhibitor LY-294002. Thus these studies have shown for the first time that insulin can induce the translocation of FAT/CD36 from an intracellular depot to the plasma membrane.This reveals a previously unknown level of regulation of fatty acid transport by insulin and may well have important consequences in furthering our understanding of the relation between fatty acid metabolism and insulin resistance.

scholarly journals FATP2 is a hepatic fatty acid transporter and peroxisomal very long-chain acyl-CoA synthetase

2010 ◽  
Vol 299 (3) ◽  
pp. E384-E393 ◽  
Author(s):  
Alaric Falcon ◽  
Holger Doege ◽  
Amy Fluitt ◽  
Bernice Tsang ◽  
Nicki Watson ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Uptake ◽  
Fatty Acid Transport ◽  
Acid Uptake ◽  
Peroxisomal Enzyme ◽  
Multifunctional Protein ◽  
Hepatic Fatty Acid ◽  
Chain Acyl ◽  
Lcfa Uptake ◽  
Long Chain

Fatty acid transport protein (FATP)2, a member of the FATP family of fatty acid uptake mediators, has independently been identified as a hepatic peroxisomal very long-chain acyl-CoA synthetase (VLACS). Here we address whether FATP2 is 1) a peroxisomal enzyme, 2) a plasma membrane-associated long-chain fatty acid (LCFA) transporter, or 3) a multifunctional protein. We found that, in mouse livers, only a minor fraction of FATP2 localizes to peroxisomes, where it contributes to approximately half of the peroxisomal VLACS activity. However, total hepatic (V)LACS activity was not significantly affected by loss of FATP2, while LCFA uptake was reduced by 40%, indicating a more prominent role in hepatic LCFA uptake. This suggests FATP2 as a potential target for a therapeutic intervention of hepatosteatosis. Adeno-associated virus 8-based short hairpin RNA expression vectors were used to achieve liver-specific FATP2 knockdown, which significantly reduced hepatosteatosis in the face of continued high-fat feeding, concomitant with improvements in liver physiology, fasting glucose, and insulin levels. Based on our findings, we propose a model in which FATP2 is a multifunctional protein that shows subcellular localization-dependent activity and is a major contributor to peroxisomal (V)LACS activity and hepatic fatty acid uptake, suggesting FATP2 as a potential novel target for the treatment of nonalcoholic fatty liver disease.

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