Fatty acid and glucose utilization in isolated, working fetal pig hearts

1983 ◽  
Vol 245 (1) ◽  
pp. E19-E23 ◽  
Author(s):  
J. C. Werner ◽  
V. Whitman ◽  
R. R. Fripp ◽  
H. G. Schuler ◽  
J. Musselman ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Glucose Uptake ◽  
Glucose Utilization ◽  
Short Chain Fatty Acids ◽  
Fatty Acid Uptake ◽  
Acid Uptake ◽  
Beta Oxidation ◽  
Tissue Concentrations ◽  
Long Chain ◽  
Fetal Pig

Fatty acid uptake and the effects of long- and short-chain fatty acids on glucose utilization were assessed in isolated perfused fetal pig hearts (0.9 gestation) in which oxygenated nutrient buffer was pumped from both ventricles at controlled pressure (55 mmHg, mean arterial pressure) and heart rate (180 beats/min). When either 1.5 mM palmitate or 1.0 mM octanoate was added to buffer containing 10 mM glucose and insulin (100 microU/ml), glucose uptake, as measured by 3H2O production from D-[2-3H]glucose, was suppressed when compared with glucose uptake in the absence of fatty acid. Increased tissue concentrations of glucose 6-phosphate, fructose 6-phosphate, and citrate in hearts perfused with buffer containing octanoate indicated active beta-oxidation and inhibition of phosphofructokinase activity when compared with hearts perfused with glucose alone. In contrast, hearts perfused with buffer containing palmitate showed no increases in these metabolic intermediates. These results suggest that suppression of glucose uptake in the presence of long-chain fatty acid was not the result of phosphofructokinase inhibition but may result from inhibition of glucose transport by palmitate. Determinations of tissue concentrations of free carnitine and carnitine derivatives indicated that, although palmitate underwent esterification to long-chain acyl carnitine in the fetal heart, it failed to undergo extensive beta-oxidation.

scholarly journals Membrane Fatty Acid Transporters as Regulators of Lipid Metabolism: Implications for Metabolic Disease

2010 ◽  
Vol 90 (1) ◽  
pp. 367-417 ◽  
Author(s):  
Jan F. C. Glatz ◽  
Joost J. F. P. Luiken ◽  
Arend Bonen
Keyword(s):  
Fatty Acid ◽  
Glucose Uptake ◽  
Contractile Activity ◽  
Dynamic Properties ◽  
Fatty Acid Uptake ◽  
The Body ◽  
Acid Uptake ◽  
Membrane Fatty Acid ◽  
Increase Glucose Uptake ◽  
Long Chain

Long-chain fatty acids and lipids serve a wide variety of functions in mammalian homeostasis, particularly in the formation and dynamic properties of biological membranes and as fuels for energy production in tissues such as heart and skeletal muscle. On the other hand, long-chain fatty acid metabolites may exert toxic effects on cellular functions and cause cell injury. Therefore, fatty acid uptake into the cell and intracellular handling need to be carefully controlled. In the last few years, our knowledge of the regulation of cellular fatty acid uptake has dramatically increased. Notably, fatty acid uptake was found to occur by a mechanism that resembles that of cellular glucose uptake. Thus, following an acute stimulus, particularly insulin or muscle contraction, specific fatty acid transporters translocate from intracellular stores to the plasma membrane to facilitate fatty acid uptake, just as these same stimuli recruit glucose transporters to increase glucose uptake. This regulatory mechanism is important to clear lipids from the circulation postprandially and to rapidly facilitate substrate provision when the metabolic demands of heart and muscle are increased by contractile activity. Studies in both humans and animal models have implicated fatty acid transporters in the pathogenesis of diseases such as the progression of obesity to insulin resistance and type 2 diabetes. As a result, membrane fatty acid transporters are now being regarded as a promising therapeutic target to redirect lipid fluxes in the body in an organ-specific fashion.

scholarly journals Arsenite Modulates Cardiac Substrate Preference by Translocation of GLUT4, But Not CD36, Independent of Mitogen-Activated Protein Kinase Signaling

Endocrinology ◽  
2006 ◽  
Vol 147 (11) ◽  
pp. 5205-5216 ◽  
Author(s):  
Joost J. F. P. Luiken ◽  
Iman Momken ◽  
Daphna D. J. Habets ◽  
Mohammed El Hasnaoui ◽  
Will A. Coumans ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Glucose Uptake ◽  
P38 Mapk ◽  
Fatty Acid Uptake ◽  
Chain Fatty Acid ◽  
Acid Uptake ◽  
Long Chain Fatty Acid ◽  
P70 S6k ◽  
Long Chain ◽  
Stimulation Of

The protein thiol-modifying agent arsenite, a potent activator of stress signaling, was used to examine the involvement of MAPKs in the regulation of cardiac substrate uptake. Arsenite strongly induced p38 MAPK phosphorylation in isolated rat cardiac myocytes but also moderately enhanced phosphorylation of p42/44 ERK and p70 S6K. At the level of cardiomyocytic substrate use, arsenite enhanced glucose uptake dose dependently up to 5.1-fold but failed to stimulate long-chain fatty acid uptake. At the substrate transporter level, arsenite stimulated the translocation of GLUT4 to the sarcolemma but failed to recruit CD36 or FABPpm. Because arsenite did not influence the intrinsic activity of glucose transporters, GLUT4 translocation is entirely responsible for the selective increase in glucose uptake by arsenite. Moreover, the nonadditivity of arsenite-induced glucose uptake and insulin-induced glucose uptake indicates that arsenite recruits GLUT4 from insulin-responsive intracellular stores. Inhibitor studies with SB203580/SB202190, PD98059, and rapamycin indicate that activation of p38 MAPK, p42/44 ERK, and p70 S6K, respectively, are not involved in arsenite-induced glucose uptake. In addition, all these kinases do not play a role in regulation of cardiac glucose and long-chain fatty acid uptake by insulin. Hence, arsenite’s selective stimulation of glucose uptake appears unrelated to its signaling actions, suggesting that arsenite acts via thiol modification of a putative intracellular protein target of arsenite within insulin-responsive GLUT4-containing stores. Because of arsenite’s selective stimulation of cardiac glucose uptake, identification of this putative target of arsenite within the GLUT4-storage compartment may indicate whether it is a target for future strategies in prevention of diabetic cardiomyopathy.

Increased FAT (fatty acid translocase)/CD36-mediated long-chain fatty acid uptake in cardiac myocytes from obese Zucker rats

2004 ◽  
Vol 32 (1) ◽  
pp. 83-85 ◽  
Author(s):  
S.L.M. Coort ◽  
J.J.F.P. Luiken ◽  
G.J. van der Vusse ◽  
A. Bonen ◽  
J.F.C. Glatz
Keyword(s):  
Fatty Acid ◽  
Glucose Uptake ◽  
Cardiac Myocytes ◽  
Fatty Acid Uptake ◽  
Chain Fatty Acid ◽  
Zucker Rats ◽  
Acid Uptake ◽  
Long Chain Fatty Acid ◽  
Obese Zucker Rats ◽  
Long Chain

Disturbed cardiac lipid homoeostasis in obesity is regarded as a key player in the development of cardiovascular diseases. In this study, we show that FAT (fatty acid translocase)/CD36-mediated LCFA (long-chain fatty acid) uptake in cardiac myocytes from young adult obese Zucker rats is markedly increased, but insensitive to insulin. Basal and insulin-induced glucose uptake rates in these myocytes are not changed, suggesting that during the development from obesity to hyperglycaemic Type II diabetes, alterations in cardiac LCFA uptake precede alterations in cardiac glucose uptake.

AMPK-mediated increase in myocardial long-chain fatty acid uptake critically depends on sarcolemmal CD36

2007 ◽  
Vol 355 (1) ◽  
pp. 204-210 ◽  
Author(s):  
Daphna D.J. Habets ◽  
Will A. Coumans ◽  
Peter J. Voshol ◽  
Marion A.M. den Boer ◽  
Maria Febbraio ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Uptake ◽  
Chain Fatty Acid ◽  
Acid Uptake ◽  
Long Chain Fatty Acid ◽  
Long Chain

scholarly journals Biocatalyst Engineering by Assembly of Fatty Acid Transport and Oxidation Activities for In Vivo Application of Cytochrome P-450BM-3 Monooxygenase

1998 ◽  
Vol 64 (10) ◽  
pp. 3784-3790 ◽  
Author(s):  
Silke Schneider ◽  
Marcel G. Wubbolts ◽  
Dominique Sanglard ◽  
Bernard Witholt
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Coenzyme A ◽  
Fatty Acid Uptake ◽  
Acid Uptake ◽  
Uptake System ◽  
Whole Cells ◽  
E Coli ◽  
Cytochrome P 450 ◽  
Long Chain

ABSTRACT The application of whole cells containing cytochrome P-450BM-3 monooxygenase [EC 1.14.14.1 ] for the bioconversion of long-chain saturated fatty acids to ω-1, ω-2, and ω-3 hydroxy fatty acids was investigated. We utilized pentadecanoic acid and studied its conversion to a mixture of 12-, 13-, and 14-hydroxypentadecanoic acids by this monooxygenase. For this purpose,Escherichia coli recombinants containing plasmid pCYP102 producing the fatty acid monooxygenase cytochrome P-450BM-3were used. To overcome inefficient uptake of pentadecanoic acid by intact E. coli cells, we made use of a cloned fatty acid uptake system from Pseudomonas oleovorans which, in contrast to the common FadL fatty acid uptake system of E. coli, does not require coupling by FadD (acyl-coenzyme A synthetase) of the imported fatty acid to coenzyme A. This system fromP. oleovorans is encoded by a gene carried by plasmid pGEc47, which has been shown to effect facilitated uptake of oleic acid in E. coli W3110 (M. Nieboer, Ph.D. thesis, University of Groningen, Groningen, The Netherlands, 1996). By using a double recombinant of E. coli K27, which is a fadDmutant and therefore unable to consume substrates or products via the β-oxidation cycle, a twofold increase in productivity was achieved. Applying cytochrome P-450BM-3 monooxygenase as a biocatalyst in whole cells does not require the exogenous addition of the costly cofactor NADPH. In combination with the coenzyme A-independent fatty acid uptake system from P. oleovorans, cytochrome P-450BM-3 recombinants appear to be useful alternatives to the enzymatic approach for the bioconversion of long-chain fatty acids to subterminal hydroxylated fatty acids.

scholarly journals Metabolic Reprogramming from Glycolysis to Fatty Acid Uptake and beta-Oxidation in Platinum-Resistant Cancer Cells

2021 ◽  
Author(s):  
Junjie Li ◽  
Yuying Tan ◽  
Guangyuan Zhao ◽  
Kai-Chih Huang ◽  
Horacio Cardenas ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Fatty Acid ◽  
Single Cell ◽  
Cancer Cell ◽  
Aerobic Glycolysis ◽  
Fatty Acid Uptake ◽  
Metabolic Reprogramming ◽  
De Novo Lipogenesis ◽  
Acid Uptake ◽  
Beta Oxidation

Increased aerobic glycolysis is widely considered as a hallmark of cancer. Yet, cancer cell metabolic reprograming during development of therapeutic resistance is under-studied. Here, through high-throughput stimulated Raman scattering imaging and single cell analysis, we found that cisplatin-resistant cells exhibit increased uptake of exogenous fatty acids, accompanied with decreased glucose uptake and de novo lipogenesis, indicating a reprogramming from glucose and glycolysis dependent to fatty acid uptake and beta-oxidation dependent anabolic and energy metabolism. A metabolic index incorporating measurements of glucose derived anabolism and fatty acid uptake correlates linearly to the level of resistance to cisplatin in ovarian cancer cell lines and in primary cells isolated from ovarian cancer patients. Mechanistically, the increased fatty acid uptake facilitates cancer cell survival under cisplatin-induced oxidative stress by enhancing energy production through beta-oxidation. Consequently, blocking fatty acid beta-oxidation by a small molecule inhibitor in combination with cisplatin or carboplatin synergistically suppressed ovarian cancer proliferation in vitro and growth of patient-derived xenograft in vivo. Collectively, these findings support a new way for rapid detection of cisplatin-resistance at single cell level and a new strategy for treatment of cisplatin-resistant tumors.

scholarly journals Protein Kinase D1 Is Essential for Contraction-induced Glucose Uptake but Is Not Involved in Fatty Acid Uptake into Cardiomyocytes

2011 ◽  
Vol 287 (8) ◽  
pp. 5871-5881 ◽  
Author(s):  
Ellen Dirkx ◽  
Robert W. Schwenk ◽  
Will A. Coumans ◽  
Nicole Hoebers ◽  
Yeliz Angin ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Protein Kinase ◽  
Glucose Uptake ◽  
Fatty Acid Uptake ◽  
Acid Uptake ◽  
Protein Kinase D1

scholarly journals Rat Long Chain Acyl-CoA Synthetase 5 Increases Fatty Acid Uptake and Partitioning to Cellular Triacylglycerol in McArdle-RH7777 Cells

2005 ◽  
Vol 281 (2) ◽  
pp. 945-950 ◽  
Author(s):  
Douglas G. Mashek ◽  
Michelle A. McKenzie ◽  
Cynthia G. Van Horn ◽  
Rosalind A. Coleman
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Uptake ◽  
Acid Uptake ◽  
Chain Acyl ◽  
Long Chain
Sign in / Sign up

Export Citation Format

Share Document