The Experts below are selected from a list of 6177 Experts worldwide ranked by ideXlab platform
Joost J. F. P. Luiken - One of the best experts on this subject based on the ideXlab platform.
-
fluorescent labelling of membrane Fatty Acid Transporter cd36 sr b2 in the extracellular loop
PLOS ONE, 2019Co-Authors: Yilin Liu, Jos L V Broers, Joost J. F. P. Luiken, Jan F. C. Glatz, Ricardo Rodriguezcalvo, Shujin Wang, Xiaoqing Zhu, Dietbert NeumannAbstract:Context Upon palmitate oversupply, membrane Fatty Acid-Transporter CD36 (SR-B2) permanently translocates from endosomal storage to the sarcolemma, inducing lipotoxicity. CD36 translocation results from endosomal alkalinisation elicited by palmitate-induced disattachment of the cytoplasmic V1-subcomplex from the membrane-integrated V0-subcomplex of vacuolar-type H+-ATPase. Objective Develop a CD36 fluorescent labeling technique as initial step towards live cell imaging. Methods Three human CD36 (hCD36) mutants were constructed via insertion of a tetracysteine motif at different positions within the extracellular domain. Constructs were lentivirally transduced for subsequent CD36 labeling with fluorescein-arsenical hairpin-binder (FlAsH). Cell imaging was combined with V0/V1 immunostaining and Western blotting. Results Transduction of hCD36-wildtype and mutants yielded corresponding proteins in HL-1 cardiomyocytes. Tetracysteine mutant-2 (hCD36-TC2) showed similar Fatty Acid uptake to wildtype. FlAsH staining revealed a speckled pattern reminiscent of endosomes. We found decreased V1 co-localization with CD36 upon high-palmitate culturing. Conversely, V0 consistently co-localized with CD36. Conclusion hCD36-TC2 is a possible candidate for application of biarsenical dyes in live imaging studies pending further investigation. Our data is compatible with V0/V1 disassembly in high-palmitate-treated cells.
-
differential translocation of the Fatty Acid Transporter fat cd36 and the glucose Transporter glut4 coordinates changes in cardiac substrate metabolism during ischemia and reperfusion
Circulation-heart Failure, 2013Co-Authors: Lisa C Heather, Joost J. F. P. Luiken, Jan F. C. Glatz, Mark A Cole, Rhys D Evans, Katharine M Pates, Helen J Atherton, Daniel R Ball, Julian L Griffin, Kieran ClarkeAbstract:Background— Fatty Acid and glucose Transporters translocate between the sarcolemma and intracellular compartments to regulate substrate metabolism acutely. We hypothesised that during ischemia Fatty Acid translocase (FAT/CD36) would translocate away from the sarcolemma to limit Fatty Acid uptake when Fatty Acid oxidation is inhibited. Methods and Results— Wistar rat hearts were perfused during preischemia, low-flow ischemia, and reperfusion, using 3H-substrates for measurement of metabolic rates, followed by metabolomic analysis and subcellular fractionation. During ischemia, there was a 32% decrease in sarcolemmal FAT/CD36 accompanied by a 95% decrease in Fatty Acid oxidation rates, with no change in intramyocardial lipids. Concomitantly, the sarcolemmal content of the glucose Transporter, GLUT4, increased by 90% during ischemia, associated with an 86% increase in glycolytic rates, 45% decrease in glycogen content, and a 3-fold increase in phosphorylated AMP-activated protein kinase. Following reperfusion, decreased sarcolemmal FAT/CD36 persisted, but Fatty Acid oxidation rates returned to preischemic levels, resulting in a 35% decrease in myocardial triglyceride content. Elevated sarcolemmal GLUT4 persisted during reperfusion; in contrast, glycolytic rates decreased to 30% of preischemic rates, accompanied by a 5-fold increase in intracellular citrate levels and restoration of glycogen content. Conclusions— During ischemia, FAT/CD36 moved away from the sarcolemma as GLUT4 moved toward the sarcolemma, associated with a shift from Fatty Acid oxidation to glycolysis, while intramyocardial lipid accumulation was prevented. This relocation was maintained during reperfusion, which was associated with replenishing glycogen stores as a priority, occurring at the expense of glycolysis and mediated by an increase in citrate levels.
-
ps9 43 overexpression of vesicle associated membrane protein 3 vamp3 protects against lipid induced inhibition of insulin stimulated glut4 translocation in cardiomyocytes
Nederlands Tijdschrift voor Diabetologie, 2012Co-Authors: Robert W. Schwenk, Laura K M Steinbusch, Ellen Dirkx, Nicole T H Hoebers, Jos L V Broers, Yeliz Angin, Will A Coumans, Jan F. C. Glatz, Joost J. F. P. LuikenAbstract:Cardiac glucose utilization is regulated by translocation of the glucose Transporter GLUT4 from intracellular stores to the sarcolemma. During lipid-induced insulin resistance, the sarcolemmal presence of the Fatty Acid Transporter CD36 increases, resulting in increased Fatty Acid uptake and elevation of intracellular lipid metabolites, which interfere with insulin-stimulated GLUT4 translocation, and consequently lead to impaired glucose utilization.
-
munc18c provides stimulus selective regulation of glut4 but not Fatty Acid Transporter trafficking in skeletal muscle
FEBS Letters, 2012Co-Authors: Swati S Jain, Joost J. F. P. Luiken, Jan F. C. Glatz, Laelie A Snook, Graham P Holloway, Debbie C Thurmond, Arend BonenAbstract:Insulin-, and contraction-induced GLUT4 and Fatty Acid (FA) Transporter translocation may share common trafficking mechanisms. Our objective was to examine the effects of partial Munc18c ablation on muscle glucose and FA transport, FA oxidation, GLUT4 and FA Transporter (FAT/CD36, FABPpm, FATP1, FATP4) trafficking to the sarcolemma, and FAT/CD36 to mitochondria. In Munc18c−/+ mice, insulin-stimulated glucose transport and GLUT4 sarcolemmal appearance were impaired, but were unaffected by contraction. Insulin- and contraction-stimulated FA transport, sarcolemmal FA Transporter appearance, and contraction-mediated mitochondrial FAT/CD36 were increased normally in Munc18c−/+ mice. Hence, Munc18c provides stimulus-specific regulation of GLUT4 trafficking, but not FA Transporter trafficking.
-
absence of Fatty Acid Transporter cd36 protects against western type diet related cardiac dysfunction following pressure overload in mice
American Journal of Physiology-endocrinology and Metabolism, 2011Co-Authors: Laura K M Steinbusch, Nicole T H Hoebers, Will A Coumans, Joost J. F. P. Luiken, Adrian Chabowski, Ronald Vlasblom, Irene O C M Vroegrijk, P J Voshol, Margriet D Ouwens, Jan F. C. GlatzAbstract:Cardiac patients often are obese and have hypertension, but in most studies these conditions are investigated separately. Here, we aimed at 1) elucidating the interaction of metabolic and mechanoph...
Arend Bonen - One of the best experts on this subject based on the ideXlab platform.
-
munc18c provides stimulus selective regulation of glut4 but not Fatty Acid Transporter trafficking in skeletal muscle
FEBS Letters, 2012Co-Authors: Swati S Jain, Joost J. F. P. Luiken, Jan F. C. Glatz, Laelie A Snook, Graham P Holloway, Debbie C Thurmond, Arend BonenAbstract:Insulin-, and contraction-induced GLUT4 and Fatty Acid (FA) Transporter translocation may share common trafficking mechanisms. Our objective was to examine the effects of partial Munc18c ablation on muscle glucose and FA transport, FA oxidation, GLUT4 and FA Transporter (FAT/CD36, FABPpm, FATP1, FATP4) trafficking to the sarcolemma, and FAT/CD36 to mitochondria. In Munc18c−/+ mice, insulin-stimulated glucose transport and GLUT4 sarcolemmal appearance were impaired, but were unaffected by contraction. Insulin- and contraction-stimulated FA transport, sarcolemmal FA Transporter appearance, and contraction-mediated mitochondrial FAT/CD36 were increased normally in Munc18c−/+ mice. Hence, Munc18c provides stimulus-specific regulation of GLUT4 trafficking, but not FA Transporter trafficking.
-
metabolic challenges reveal impaired Fatty Acid metabolism and translocation of fat cd36 but not fabppm in obese zucker rat muscle
American Journal of Physiology-endocrinology and Metabolism, 2007Co-Authors: Adrian Chabowski, Joost J. F. P. Luiken, Jan F. C. Glatz, Narendra N Tandon, Jorge Callesescandon, Arend BonenAbstract:We examined, in muscle of lean and obese Zucker rats, basal, insulin-induced, and contraction-induced Fatty Acid Transporter translocation and Fatty Acid uptake, esterification, and oxidation. In l...
-
metabolic challenges reveal impaired Fatty Acid metabolism and translocation of fat cd36 but not fabppm in obese zucker rat muscle
American Journal of Physiology-endocrinology and Metabolism, 2007Co-Authors: Xiaoxia Han, Joost J. F. P. Luiken, Jan F. C. Glatz, Narendra N Tandon, Adrian Chabowski, Jorge Callesescandon, Arend BonenAbstract:We examined, in muscle of lean and obese Zucker rats, basal, insulin-induced, and contraction-induced Fatty Acid Transporter translocation and Fatty Acid uptake, esterification, and oxidation. In lean rats, insulin and contraction induced the translocation of the Fatty Acid Transporter FAT/CD36 (43 and 41%, respectively) and plasma membrane-associated Fatty Acid binding protein (FABPpm; 19 and 60%) and increased Fatty Acid uptake (63 and 40%, respectively). Insulin and contraction increased lean muscle palmitate esterification and oxidation 72 and 61%, respectively. In obese rat muscle, basal levels of sarcolemmal FAT/CD36 (+33%) and FABPpm (+14%) and Fatty Acid uptake (+30%) and esterification (+32%) were increased, whereas Fatty Acid oxidation was reduced (-28%). Insulin stimulation of obese rat muscle increased plasmalemmal FABPpm (+15%) but not plasmalemmal FAT/CD36, blunted Fatty Acid uptake and esterification, and failed to reduce Fatty Acid oxidation. In contracting obese rat muscle, the increases in Fatty Acid uptake and esterification and FABPpm translocation were normal, but FAT/CD36 translocation was impaired and Fatty Acid oxidation was blunted. There was no relationship between plasmalemmal Fatty Acid Transporters and palmitate partitioning. In conclusion, Fatty Acid metabolism is impaired at several levels in muscles of obese Zucker rats; specifically, they are 1) insulin resistant with respect to FAT/CD36 translocation and Fatty Acid uptake, esterification, and oxidation and 2) contraction resistant with respect to Fatty Acid oxidation and FAT/CD36 translocation, but, conversely, 3) obese muscles are neither insulin nor contraction resistant at the level of FABPpm. Finally, 4) there is no evidence that plasmalemmal Fatty Acid Transporters contribute to the channeling of Fatty Acids to specific metabolic destinations within the muscle.
-
hypoxia induced Fatty Acid Transporter translocation increases Fatty Acid transport and contributes to lipid accumulation in the heart
FEBS Letters, 2006Co-Authors: Narendra N Tandon, Adrian Chabowski, Jorge Callesescandon, Jan Gorski, Arend BonenAbstract:Protein-mediated LCFA transport across plasma membranes is highly regulated by the Fatty Acid Transporters FAT/CD36 and FABPpm. Physiologic stimuli (insulin stimulation, AMP kinase activation) induce the translocation of one or both Transporters to the plasma membrane and increase the rate of LCFA transport. In the hypoxic/ischemic heart, intramyocardial lipid accumulation has been attributed to a reduced rate of Fatty Acid oxidation. However, since acute hypoxia (15 min) activates AMPK, we examined whether an increased accumulation of intramyocardial lipid during hypoxia was also attributable to an increased rate of LCFA uptake as a result AMPK-induced translocation of FAT/CD36 and FABPpm. In cardiac myocytes, hypoxia (15 min) induced the redistribution of FAT/CD36 from an intracellular pool (LDM) (−25%, P < 0.05) to the plasma membranes (PM) (+54%, P < 0.05). Hypoxia also induced an increase in FABPpm at the PM (+56%, P < 0.05) and a concomitant FABPpm reduction in the LDM (−24%, P < 0.05). Similarly, in intact, Langendorff perfused hearts, hypoxia induced the translocation of a both FAT/CD36 and FABPpm to the PM (+66% and +61%, respectively, P < 0.05), with a concomitant decline in FAT/CD36 and FABPpm in the LDM (−24% and −23%, respectively, P < 0.05). Importantly, the increased plasmalemmal content of these Transporters was associated with increases in the initial rates of palmitate uptake into cardiac myocytes (+40%, P < 0.05). Acute hypoxia also redirected palmitate into intracellular lipid pools, mainly to PL and TG (+48% and +28%, respectively, P < 0.05), while Fatty Acid oxidation was reduced (−35%, P < 0.05). Thus, our data indicate that the increased intracellular lipid accumulation in hypoxic hearts is attributable to both: (a) a reduced rate of Fatty Acid oxidation and (b) an increased rate of Fatty Acid transport into the heart, the latter being attributable to a hypoxia-induced translocation of Fatty Acid Transporters.
-
the Fatty Acid Transporter fat cd36 is upregulated in subcutaneous and visceral adipose tissues in human obesity and type 2 diabetes
International Journal of Obesity, 2006Co-Authors: Arend Bonen, Joost J. F. P. Luiken, Narendra N Tandon, J F C Glatz, George J F HeigenhauserAbstract:The Fatty Acid Transporter FAT/CD36 is upregulated in subcutaneous and visceral adipose tissues in human obesity and type 2 diabetes
Jan F. C. Glatz - One of the best experts on this subject based on the ideXlab platform.
-
fluorescent labelling of membrane Fatty Acid Transporter cd36 sr b2 in the extracellular loop
PLOS ONE, 2019Co-Authors: Yilin Liu, Jos L V Broers, Joost J. F. P. Luiken, Jan F. C. Glatz, Ricardo Rodriguezcalvo, Shujin Wang, Xiaoqing Zhu, Dietbert NeumannAbstract:Context Upon palmitate oversupply, membrane Fatty Acid-Transporter CD36 (SR-B2) permanently translocates from endosomal storage to the sarcolemma, inducing lipotoxicity. CD36 translocation results from endosomal alkalinisation elicited by palmitate-induced disattachment of the cytoplasmic V1-subcomplex from the membrane-integrated V0-subcomplex of vacuolar-type H+-ATPase. Objective Develop a CD36 fluorescent labeling technique as initial step towards live cell imaging. Methods Three human CD36 (hCD36) mutants were constructed via insertion of a tetracysteine motif at different positions within the extracellular domain. Constructs were lentivirally transduced for subsequent CD36 labeling with fluorescein-arsenical hairpin-binder (FlAsH). Cell imaging was combined with V0/V1 immunostaining and Western blotting. Results Transduction of hCD36-wildtype and mutants yielded corresponding proteins in HL-1 cardiomyocytes. Tetracysteine mutant-2 (hCD36-TC2) showed similar Fatty Acid uptake to wildtype. FlAsH staining revealed a speckled pattern reminiscent of endosomes. We found decreased V1 co-localization with CD36 upon high-palmitate culturing. Conversely, V0 consistently co-localized with CD36. Conclusion hCD36-TC2 is a possible candidate for application of biarsenical dyes in live imaging studies pending further investigation. Our data is compatible with V0/V1 disassembly in high-palmitate-treated cells.
-
differential translocation of the Fatty Acid Transporter fat cd36 and the glucose Transporter glut4 coordinates changes in cardiac substrate metabolism during ischemia and reperfusion
Circulation-heart Failure, 2013Co-Authors: Lisa C Heather, Joost J. F. P. Luiken, Jan F. C. Glatz, Mark A Cole, Rhys D Evans, Katharine M Pates, Helen J Atherton, Daniel R Ball, Julian L Griffin, Kieran ClarkeAbstract:Background— Fatty Acid and glucose Transporters translocate between the sarcolemma and intracellular compartments to regulate substrate metabolism acutely. We hypothesised that during ischemia Fatty Acid translocase (FAT/CD36) would translocate away from the sarcolemma to limit Fatty Acid uptake when Fatty Acid oxidation is inhibited. Methods and Results— Wistar rat hearts were perfused during preischemia, low-flow ischemia, and reperfusion, using 3H-substrates for measurement of metabolic rates, followed by metabolomic analysis and subcellular fractionation. During ischemia, there was a 32% decrease in sarcolemmal FAT/CD36 accompanied by a 95% decrease in Fatty Acid oxidation rates, with no change in intramyocardial lipids. Concomitantly, the sarcolemmal content of the glucose Transporter, GLUT4, increased by 90% during ischemia, associated with an 86% increase in glycolytic rates, 45% decrease in glycogen content, and a 3-fold increase in phosphorylated AMP-activated protein kinase. Following reperfusion, decreased sarcolemmal FAT/CD36 persisted, but Fatty Acid oxidation rates returned to preischemic levels, resulting in a 35% decrease in myocardial triglyceride content. Elevated sarcolemmal GLUT4 persisted during reperfusion; in contrast, glycolytic rates decreased to 30% of preischemic rates, accompanied by a 5-fold increase in intracellular citrate levels and restoration of glycogen content. Conclusions— During ischemia, FAT/CD36 moved away from the sarcolemma as GLUT4 moved toward the sarcolemma, associated with a shift from Fatty Acid oxidation to glycolysis, while intramyocardial lipid accumulation was prevented. This relocation was maintained during reperfusion, which was associated with replenishing glycogen stores as a priority, occurring at the expense of glycolysis and mediated by an increase in citrate levels.
-
ps9 43 overexpression of vesicle associated membrane protein 3 vamp3 protects against lipid induced inhibition of insulin stimulated glut4 translocation in cardiomyocytes
Nederlands Tijdschrift voor Diabetologie, 2012Co-Authors: Robert W. Schwenk, Laura K M Steinbusch, Ellen Dirkx, Nicole T H Hoebers, Jos L V Broers, Yeliz Angin, Will A Coumans, Jan F. C. Glatz, Joost J. F. P. LuikenAbstract:Cardiac glucose utilization is regulated by translocation of the glucose Transporter GLUT4 from intracellular stores to the sarcolemma. During lipid-induced insulin resistance, the sarcolemmal presence of the Fatty Acid Transporter CD36 increases, resulting in increased Fatty Acid uptake and elevation of intracellular lipid metabolites, which interfere with insulin-stimulated GLUT4 translocation, and consequently lead to impaired glucose utilization.
-
munc18c provides stimulus selective regulation of glut4 but not Fatty Acid Transporter trafficking in skeletal muscle
FEBS Letters, 2012Co-Authors: Swati S Jain, Joost J. F. P. Luiken, Jan F. C. Glatz, Laelie A Snook, Graham P Holloway, Debbie C Thurmond, Arend BonenAbstract:Insulin-, and contraction-induced GLUT4 and Fatty Acid (FA) Transporter translocation may share common trafficking mechanisms. Our objective was to examine the effects of partial Munc18c ablation on muscle glucose and FA transport, FA oxidation, GLUT4 and FA Transporter (FAT/CD36, FABPpm, FATP1, FATP4) trafficking to the sarcolemma, and FAT/CD36 to mitochondria. In Munc18c−/+ mice, insulin-stimulated glucose transport and GLUT4 sarcolemmal appearance were impaired, but were unaffected by contraction. Insulin- and contraction-stimulated FA transport, sarcolemmal FA Transporter appearance, and contraction-mediated mitochondrial FAT/CD36 were increased normally in Munc18c−/+ mice. Hence, Munc18c provides stimulus-specific regulation of GLUT4 trafficking, but not FA Transporter trafficking.
-
absence of Fatty Acid Transporter cd36 protects against western type diet related cardiac dysfunction following pressure overload in mice
American Journal of Physiology-endocrinology and Metabolism, 2011Co-Authors: Laura K M Steinbusch, Nicole T H Hoebers, Will A Coumans, Joost J. F. P. Luiken, Adrian Chabowski, Ronald Vlasblom, Irene O C M Vroegrijk, P J Voshol, Margriet D Ouwens, Jan F. C. GlatzAbstract:Cardiac patients often are obese and have hypertension, but in most studies these conditions are investigated separately. Here, we aimed at 1) elucidating the interaction of metabolic and mechanoph...
Andreas Stahl - One of the best experts on this subject based on the ideXlab platform.
-
fatp2 is a hepatic Fatty Acid Transporter and peroxisomal very long chain acyl coa synthetase
American Journal of Physiology-endocrinology and Metabolism, 2010Co-Authors: Alaric Falcon, Bernice Tsang, Holger Doege, Amy Fluitt, Nicki Watson, Mark A Kay, Andreas StahlAbstract: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.
-
silencing of hepatic Fatty Acid Transporter protein 5 in vivo reverses diet induced non alcoholic Fatty liver disease and improves hyperglycemia
Journal of Biological Chemistry, 2008Co-Authors: Angelica M Ortegon, Bernice Tsang, Holger Doege, Alaric Falcon, Mark A Kay, Dirk Grimm, Theresa A Storm, Melissa Kazantzis, Andreas StahlAbstract:Non-alcoholic Fatty liver disease is a serious health problem linked to obesity and type 2 diabetes. To investigate the biological outcome and therapeutic potential of hepatic Fatty Acid uptake inhibition, we utilized an adeno-associated virus-mediated RNA interference technique to knock down the expression of hepatic Fatty Acid transport protein 5 in vivo prior to or after establishing non-alcoholic Fatty liver disease in mice. Using this approach, we demonstrate here the ability to achieve specific, non-toxic, and persistent knockdown of Fatty Acid transport protein 5 in mouse livers from a single adeno-associated virus injection, resulting in a marked reduction of hepatic dietary Fatty Acid uptake, reduced caloric uptake, and concomitant protection from diet-induced non-alcoholic Fatty liver disease. Importantly, knockdown of Fatty Acid transport protein 5 was also able to reverse already established non-alcoholic Fatty liver disease, resulting in significantly improved whole-body glucose homeostasis. Thus, continued activity of hepatic Fatty Acid transport protein 5 is required to sustain caloric uptake and Fatty Acid flux into the liver during high fat feeding and may present a novel avenue for the treatment of non-alcoholic Fatty liver disease.
-
fatp1 is an insulin sensitive Fatty Acid Transporter involved in diet induced obesity
Molecular and Cellular Biology, 2006Co-Authors: Angelica M Ortegon, Bernice Tsang, Holger Doege, Kenneth R Feingold, Andreas StahlAbstract:Fatty Acid transport protein 1 (FATP1), a member of the FATP/Slc27 protein family, enhances the cellular uptake of long-chain Fatty Acids (LCFAs) and is expressed in several insulin-sensitive tissues. In adipocytes and skeletal muscle, FATP1 translocates from an intracellular compartment to the plasma membrane in response to insulin. Here we show that insulin-stimulated Fatty Acid uptake is completely abolished in FATP1-null adipocytes and greatly reduced in skeletal muscle of FATP1-knockout animals while basal LCFA uptake by both tissues was unaffected. Moreover, loss of FATP1 function altered regulation of postprandial serum LCFA, causing a redistribution of lipids from adipocyte tissue and muscle to the liver, and led to a complete protection from diet-induced obesity and insulin desensitization. This is the first in vivo evidence that insulin can regulate the uptake of LCFA by tissues via FATP1 activation and that FATPs determine the tissue distribution of dietary lipids. The strong protection against diet-induced obesity and insulin desensitization observed in FATP1-null animals suggests FATP1 as a novel antidiabetic target.
-
identification of the major intestinal Fatty Acid transport protein
Molecular Cell, 1999Co-Authors: Andreas Stahl, Nicki Watson, David Hirsch, Ruth E Gimeno, Sandhya Punreddy, Shraddha Patel, Mariana Kotler, Alejandra Raimondi, Louis A Tartaglia, Harvey F LodishAbstract:While intestinal transport systems for metabolites such as carbohydrates have been well characterized, the molecular mechanisms of Fatty Acid (FA) transport across the apical plasmalemma of enterocytes have remained largely unclear. Here, we show that FATP4, a member of a large family of FA transport proteins (FATPs), is expressed at high levels on the apical side of mature enterocytes in the small intestine. Further, overexpression of FATP4 in 293 cells facilitates uptake of long chain FAs with the same specificity as enterocytes, while reduction of FATP4 expression in primary enterocytes by antisense oligonucleotides inhibits FA uptake by 50%. This suggests that FATP4 is the principal Fatty Acid Transporter in enterocytes and may constitute a novel target for antiobesity therapy.
Narendra N Tandon - One of the best experts on this subject based on the ideXlab platform.
-
metabolic challenges reveal impaired Fatty Acid metabolism and translocation of fat cd36 but not fabppm in obese zucker rat muscle
American Journal of Physiology-endocrinology and Metabolism, 2007Co-Authors: Adrian Chabowski, Joost J. F. P. Luiken, Jan F. C. Glatz, Narendra N Tandon, Jorge Callesescandon, Arend BonenAbstract:We examined, in muscle of lean and obese Zucker rats, basal, insulin-induced, and contraction-induced Fatty Acid Transporter translocation and Fatty Acid uptake, esterification, and oxidation. In l...
-
metabolic challenges reveal impaired Fatty Acid metabolism and translocation of fat cd36 but not fabppm in obese zucker rat muscle
American Journal of Physiology-endocrinology and Metabolism, 2007Co-Authors: Xiaoxia Han, Joost J. F. P. Luiken, Jan F. C. Glatz, Narendra N Tandon, Adrian Chabowski, Jorge Callesescandon, Arend BonenAbstract:We examined, in muscle of lean and obese Zucker rats, basal, insulin-induced, and contraction-induced Fatty Acid Transporter translocation and Fatty Acid uptake, esterification, and oxidation. In lean rats, insulin and contraction induced the translocation of the Fatty Acid Transporter FAT/CD36 (43 and 41%, respectively) and plasma membrane-associated Fatty Acid binding protein (FABPpm; 19 and 60%) and increased Fatty Acid uptake (63 and 40%, respectively). Insulin and contraction increased lean muscle palmitate esterification and oxidation 72 and 61%, respectively. In obese rat muscle, basal levels of sarcolemmal FAT/CD36 (+33%) and FABPpm (+14%) and Fatty Acid uptake (+30%) and esterification (+32%) were increased, whereas Fatty Acid oxidation was reduced (-28%). Insulin stimulation of obese rat muscle increased plasmalemmal FABPpm (+15%) but not plasmalemmal FAT/CD36, blunted Fatty Acid uptake and esterification, and failed to reduce Fatty Acid oxidation. In contracting obese rat muscle, the increases in Fatty Acid uptake and esterification and FABPpm translocation were normal, but FAT/CD36 translocation was impaired and Fatty Acid oxidation was blunted. There was no relationship between plasmalemmal Fatty Acid Transporters and palmitate partitioning. In conclusion, Fatty Acid metabolism is impaired at several levels in muscles of obese Zucker rats; specifically, they are 1) insulin resistant with respect to FAT/CD36 translocation and Fatty Acid uptake, esterification, and oxidation and 2) contraction resistant with respect to Fatty Acid oxidation and FAT/CD36 translocation, but, conversely, 3) obese muscles are neither insulin nor contraction resistant at the level of FABPpm. Finally, 4) there is no evidence that plasmalemmal Fatty Acid Transporters contribute to the channeling of Fatty Acids to specific metabolic destinations within the muscle.
-
hypoxia induced Fatty Acid Transporter translocation increases Fatty Acid transport and contributes to lipid accumulation in the heart
FEBS Letters, 2006Co-Authors: Narendra N Tandon, Adrian Chabowski, Jorge Callesescandon, Jan Gorski, Arend BonenAbstract:Protein-mediated LCFA transport across plasma membranes is highly regulated by the Fatty Acid Transporters FAT/CD36 and FABPpm. Physiologic stimuli (insulin stimulation, AMP kinase activation) induce the translocation of one or both Transporters to the plasma membrane and increase the rate of LCFA transport. In the hypoxic/ischemic heart, intramyocardial lipid accumulation has been attributed to a reduced rate of Fatty Acid oxidation. However, since acute hypoxia (15 min) activates AMPK, we examined whether an increased accumulation of intramyocardial lipid during hypoxia was also attributable to an increased rate of LCFA uptake as a result AMPK-induced translocation of FAT/CD36 and FABPpm. In cardiac myocytes, hypoxia (15 min) induced the redistribution of FAT/CD36 from an intracellular pool (LDM) (−25%, P < 0.05) to the plasma membranes (PM) (+54%, P < 0.05). Hypoxia also induced an increase in FABPpm at the PM (+56%, P < 0.05) and a concomitant FABPpm reduction in the LDM (−24%, P < 0.05). Similarly, in intact, Langendorff perfused hearts, hypoxia induced the translocation of a both FAT/CD36 and FABPpm to the PM (+66% and +61%, respectively, P < 0.05), with a concomitant decline in FAT/CD36 and FABPpm in the LDM (−24% and −23%, respectively, P < 0.05). Importantly, the increased plasmalemmal content of these Transporters was associated with increases in the initial rates of palmitate uptake into cardiac myocytes (+40%, P < 0.05). Acute hypoxia also redirected palmitate into intracellular lipid pools, mainly to PL and TG (+48% and +28%, respectively, P < 0.05), while Fatty Acid oxidation was reduced (−35%, P < 0.05). Thus, our data indicate that the increased intracellular lipid accumulation in hypoxic hearts is attributable to both: (a) a reduced rate of Fatty Acid oxidation and (b) an increased rate of Fatty Acid transport into the heart, the latter being attributable to a hypoxia-induced translocation of Fatty Acid Transporters.
-
the Fatty Acid Transporter fat cd36 is upregulated in subcutaneous and visceral adipose tissues in human obesity and type 2 diabetes
International Journal of Obesity, 2006Co-Authors: Arend Bonen, Joost J. F. P. Luiken, Narendra N Tandon, J F C Glatz, George J F HeigenhauserAbstract:The Fatty Acid Transporter FAT/CD36 is upregulated in subcutaneous and visceral adipose tissues in human obesity and type 2 diabetes
-
tissue specific and Fatty Acid Transporter specific changes in heart and soleus muscle over a 1 yr period
Molecular and Cellular Biochemistry, 2006Co-Authors: Arend Bonen, Jan F. C. Glatz, Narendra N Tandon, James G Nickerson, Iman Momken, Adrian Chabowski, Jorge Callesescandon, Joost J. F. P. LuikenAbstract:Rates of Fatty Acid oxidation increase rapidly in both rat heart and skeletal muscle in the early postnatal period. Therefore, we examined in heart and soleus muscle, (a) whether there were rapid changes in Fatty Acid Transporter (FAT/CD36, FABPpm) mRNA and protein expression early in life (days 10 –36) and thereafter (days 84, 160, 365), and (b) whether the rates of Fatty Acid transport and the plasmalemmal content of FAT/CD36 and FABPpm were altered. Protein expression was altered rapidly from day 10–36 in both heart (FAT/CD36 only, +21%, P < 0.05)) and soleus muscle (FAT/CD36 + 100%, P < 0.05; FABPpm −20%, P < 0.05), with no further changes thereafter (P < 0.05). Rates of Fatty Acid transport (day 10 vs day 160) were increased in heart (+33%, P < 0.05) and muscle (+85%, P < 0.05), and were associated with concomitant increases in plasmalemmal FABPpm (+44%, P < 0.05) and FAT/CD36 (+16%, P < 0.05) in the heart, and only plasmalemmal FAT/CD36 in muscle (+90%, P < 0.05). Therefore, known changes in the rates of Fatty Acid oxidation in heart and muscle early in life appear to be accompanied by a concurrent upregulation in the rates of Fatty Acid transport and the expression of FAT/CD36 in heart and muscle, as well as an increase in plasmalemmal FAT/CD36 and FABPpm in the heart, and only plasmalemmal FAT/CD36 in soleus muscle. We speculate that the rapid upregulation of Fatty Acid transport rates in heart and muscle are needed to support the increased rates of Fatty oxidation that have been previously observed in these tissues.
