scholarly journals FAT/CD36-mediated Long-Chain Fatty Acid Uptake in Adipocytes Requires Plasma Membrane Rafts

2005 ◽  
Vol 16 (1) ◽  
pp. 24-31 ◽  
Author(s):  
Jürgen Pohl ◽  
Axel Ring ◽  
Ümine Korkmaz ◽  
Robert Ehehalt ◽  
Wolfgang Stremmel
Keyword(s):  
Plasma Membrane ◽  
Oleic Acid ◽  
Fatty Acid ◽  
Lipid Rafts ◽  
Chain Fatty Acid ◽  
Dominant Negative Mutant ◽  
Acid Uptake ◽  
Long Chain Fatty Acid ◽  
Lcfa Uptake ◽  
Long Chain

We previously reported that lipid rafts are involved in long-chain fatty acid (LCFA) uptake in 3T3-L1 adipocytes. The present data show that LCFA uptake does not depend on caveolae endocytosis because expression of a dominant negative mutant of dynamin had no effect on uptake of [3H]oleic acid, whereas it effectively prevented endocytosis of cholera toxin. Isolation of detergent-resistant membranes (DRMs) from 3T3-L1 cell homogenates revealed that FAT/CD36 was expressed in both DRMs and detergent-soluble membranes (DSMs), whereas FATP1 and FATP4 were present only in DSMs but not DRMs. Disruption of lipid rafts by cyclodextrin and specific inhibition of FAT/CD36 by sulfo-N-succinimidyl oleate (SSO) significantly decreased uptake of [3H]oleic acid, but simultaneous treatment had no additional or synergistic effects, suggesting that both treatments target the same mechanism. Indeed, subcellular fractionation demonstrated that plasma membrane fatty acid translocase (FAT/CD36) is exclusively located in lipid rafts, whereas intracellular FAT/CD36 cofractionated with DSMs. Binding assays confirmed that [3H]SSO predominantly binds to FAT/CD36 within plasma membrane DRMs. In conclusion, our data strongly suggest that FAT/CD36 mediates raft-dependent LCFA uptake. Plasma membrane lipid rafts might control LCFA uptake by regulating surface availability of FAT/CD36.

scholarly journals Etomoxir-induced partial carnitine palmitoyltransferase-I (CPT-I) inhibition in vivo does not alter cardiac long-chain fatty acid uptake and oxidation rates

2009 ◽  
Vol 419 (2) ◽  
pp. 447-455 ◽  
Author(s):  
Joost J. F. P. Luiken ◽  
Hanneke E. C. Niessen ◽  
Susan L. M. Coort ◽  
Nicole Hoebers ◽  
Will A. Coumans ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Chain Fatty Acid ◽  
Carnitine Palmitoyltransferase ◽  
Acid Uptake ◽  
Long Chain Fatty Acid ◽  
Fatty Acid Binding ◽  
Carnitine Palmitoyltransferase I ◽  
Cpt I ◽  
Lcfa Uptake ◽  
Long Chain

Although CPT-I (carnitine palmitoyltransferase-I) is generally regarded to present a major rate-controlling site in mitochondrial β-oxidation, it is incompletely understood whether CPT-I is rate-limiting in the overall LCFA (long-chain fatty acid) flux in the heart. Another important site of regulation of the LCFA flux in the heart is trans-sarcolemmal LCFA transport facilitated by CD36 and FABPpm (plasma membrane fatty acid-binding protein). Therefore, we explored to what extent a chronic pharmacological blockade of the LCFA flux at the level of mitochondrial entry of LCFA-CoA would affect sarcolemmal LCFA uptake. Rats were injected daily with saline or etomoxir, a specific CPT-I inhibitor, for 8 days at 20 mg/kg of body mass. Etomoxir-treated rats displayed a 44% reduced cardiac CPT-I activity. Sarcolemmal contents of CD36 and FABPpm, as well as the LCFA transport capacity, were not altered in the hearts of etomoxir-treated versus control rats. Furthermore, rates of LCFA uptake and oxidation, and glucose uptake by cardiac myocytes from etomoxir-treated rats were not different from control rats, neither under basal nor under acutely induced maximal metabolic demands. Finally, hearts from etomoxir-treated rats did not display triacylglycerol accumulation. Therefore CPT-I appears not to present a major rate-controlling site in total cardiac LCFA flux. It is likely that sarcolemmal LCFA entry rather than mitochondrial LCFA-CoA entry is a promising target for normalizing LCFA flux in cardiac metabolic diseases.

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 Phosphatidylinositol 3-kinase-dependent insulin regulation of long-chain fatty acid (LCFA) metabolism in L6 muscle cells: involvement of atypical protein kinase C-ζ in LCFA uptake but not oxidation

2008 ◽  
Vol 198 (2) ◽  
pp. 375-384 ◽  
Author(s):  
Karen R Kelly ◽  
Chin K Sung ◽  
Marcia J Abbott ◽  
Lorraine P Turcotte
Keyword(s):  
Protein Kinase C ◽  
Fatty Acid ◽  
Protein Kinase ◽  
Chain Fatty Acid ◽  
Phosphatidylinositol 3 Kinase ◽  
Long Chain Fatty Acid ◽  
Atypical Protein Kinase ◽  
Kinase C ◽  
Lcfa Uptake ◽  
Long Chain

Insulin is important in the regulation of muscle metabolism. However, its role in the regulation of muscle long-chain fatty acid (LCFA) metabolism, independent of glucose, is not clear. To determine whether insulin regulates LCFA metabolism independent of glucose and if so, via which signaling pathway, L6 myotubes were incubated, in the presence or absence of insulin (100 nM) and with either an inhibitor of phosphatidylinositol 3-kinase (PI3K) (wortmannin (W), 50 nM), protein kinase B (PKB)/Akt (A, 10 μM), or atypical protein kinase C-ζ (aPKC-ζ) (mP, 100 μM). LCFA kinetic parameters were measured via incubation with [1-14C]palmitate. Basal LCFA uptake was found to increase linearly with time (1–60 min) and concentration (50–750 μM). LCFA uptake increased in the presence of insulin and was maximum at 10 nM (P<0.05). Wortmannin prevented the insulin-induced increase in LCFA uptake and decrease in LCFA oxidation. While mP abolished the insulin-induced increase in LCFA uptake, it did not prevent the insulin-induced decrease in LCFA oxidation. None of the variables were affected by Akt inhibition. These results suggest a direct effect of insulin on LCFA metabolism in muscle cells, and that downstream of PI3K, aPKC-ζ, but not PKB/Akt mediates the effects of insulin on LCFA uptake but not oxidation.

Crucial role for LKB1 to AMPKα2 axis in the regulation of CD36-mediated long-chain fatty acid uptake into cardiomyocytes☆

2009 ◽  
Vol 1791 (3) ◽  
pp. 212-219 ◽  
Author(s):  
Daphna D.J. Habets ◽  
Will A. Coumans ◽  
Mohammed El Hasnaoui ◽  
Elham Zarrinpashneh ◽  
Luc Bertrand ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Crucial Role ◽  
Fatty Acid Uptake ◽  
Chain Fatty Acid ◽  
Acid Uptake ◽  
Long Chain Fatty Acid ◽  
Long Chain
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