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Protein mediated fatty acid uptake: Synergy between CD36/FAT-facilitated transport and acyl-CoA synthetase-driven metabolism

Published on Mar 1, 2014in Archives of Biochemistry and Biophysics3.56
· DOI :10.1016/j.abb.2014.01.025
Hannah Schneider2
Estimated H-index: 2
(Heidelberg University),
Sarah Staudacher2
Estimated H-index: 2
(Heidelberg University)
+ 3 AuthorsJoachim Füllekrug28
Estimated H-index: 28
(Heidelberg University)
Cite
Abstract
Abstract The mechanism of cellular fatty acid uptake is highly relevant for basic and clinical research. Previous work has demonstrated that fatty acid uptake is facilitated by cell surface membrane proteins as well as by intracellularly localized enzymes. Here, the exogenous expression of the CD36/FAT glycoprotein and the acyl-CoA synthetases FATP4 and ACSL1 in MDCK cells was quantified by comparison to recombinant proteins, and related to the corresponding increases of fatty acid uptake. At the molecular level, CD36/FAT was 30-fold more efficient than either FATP4 or ACSL1 in enhancing fatty acid uptake. Remarkably, co-expression of CD36/FAT with FATP4 or ACSL1 led to a higher increase of fatty acid uptake than expected from the combined individual contributions, whereas co-expression of FATP4 and ACSL1 did not. Immunofluorescence microscopy confirmed the plasma membrane localization of CD36/FAT and the intracellular localization of FATP4 to the endoplasmic reticulum, and of ACSL1 to mitochondria. Concluding, we suggest that fatty acid uptake in our model system is organized by two spatially distinct but synergistic mechanisms: the cell surface protein CD36/FAT directly facilitates fatty acid transport across the plasma membrane, whereas the intracellular acyl-CoA synthetases FATP4 and ACSL1 enhance fatty acid uptake indirectly by metabolic trapping.
  • References (53)
  • Citations (14)
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References53
Newest
Published on Sep 14, 2012in PLOS ONE2.78
Tianzuo Zhan8
Estimated H-index: 8
(Heidelberg University),
Margarete Poppelreuther5
Estimated H-index: 5
(Heidelberg University)
+ 1 AuthorsJoachim Füllekrug28
Estimated H-index: 28
(Heidelberg University)
Long chain acyl-CoA synthetases are essential enzymes of lipid metabolism, and have also been implicated in the cellular uptake of fatty acids. It is controversial if some or all of these enzymes have an additional function as fatty acid transporters at the plasma membrane. The most abundant acyl-CoA synthetases in adipocytes are FATP1, ACSVL4/FATP4 and ACSL1. Previous studies have suggested that they increase fatty acid uptake by direct transport across the plasma membrane. Here, we used a gain...
Published on Jul 1, 2012in Physiological Reviews24.25
Nada A. Abumrad58
Estimated H-index: 58
,
Nicholas O. Davidson38
Estimated H-index: 38
Intestinal lipid transport plays a central role in fat homeostasis. Here we review the pathways regulating intestinal absorption and delivery of dietary and biliary lipid substrates, principally long-chain fatty acid, cholesterol, and other sterols. We discuss the regulation and functions of CD36 in fatty acid absorption, NPC1L1 in cholesterol absorption, as well as other lipid transporters including FATP4 and SRB1. We discuss the pathways of intestinal sterol efflux via ABCG5/G8 and ABCA1 as we...
Published on Jan 1, 2012in Frontiers in Physiology3.20
Joachim Füllekrug28
Estimated H-index: 28
(Heidelberg University),
Robert Ehehalt25
Estimated H-index: 25
(Heidelberg University),
Margarete Poppelreuther5
Estimated H-index: 5
(Heidelberg University)
The mechanism of fatty acid uptake is of high interest for basic research and clinical interventions. Recently we showed that mammalian long chain fatty acyl-CoA synthetases (ACS) are not only essential enzymes for lipid metabolism but are also involved in cellular fatty acid uptake. Overexpression, RNAi depletion or hormonal stimulation of ACS enzymes lead to corresponding changes of fatty acid uptake. Remarkably, ACS are not localized to the plasma membrane where fatty acids are entering the c...
Margarete Digel5
Estimated H-index: 5
,
Simone Staffer3
Estimated H-index: 3
+ 3 AuthorsJoachim Füllekrug28
Estimated H-index: 28
The function of membrane proteins in long-chain fatty acid transport is controversial. The acyl-CoA synthetase fatty acid transport protein-4 (FATP4) has been suggested to facilitate fatty acid uptake indirectly by its enzymatic activity, or directly by transport across the plasma membrane. Here, we investigated the function of FATP4 in basal and insulin mediated fatty acid uptake in C2C12 muscle cells, a model system relevant for fatty acid metabolism. Stable expression of exogenous FATP4 resul...
Published on Jul 15, 2011in Journal of Biological Chemistry
Thi Tran3
Estimated H-index: 3
,
Hélène Poirier13
Estimated H-index: 13
+ 9 AuthorsNada A. Abumrad58
Estimated H-index: 58
The membrane glycoprotein CD36 binds nanomolar concentrations of long chain fatty acids (LCFA) and is highly expressed on the luminal surface of enterocytes. CD36 deficiency reduces chylomicron production through unknown mechanisms. In this report, we provide novel insights into some of the underlying mechanisms. Our in vivo data demonstrate that CD36 gene deletion in mice does not affect LCFA uptake and subsequent esterification into triglycerides by the intestinal mucosa exposed to the micella...
Published on Jan 1, 2011in International Journal of Medical Sciences2.33
Julia Krammer1
Estimated H-index: 1
,
Margarete Digel5
Estimated H-index: 5
+ 3 AuthorsRobert Ehehalt25
Estimated H-index: 25
(Heidelberg University)
Background: Understanding the mechanisms of long chain fatty acid (LCFA) uptake in hepatic cells is of high medical importance to treat and to prevent fatty liver disease (FLD). ACSs (Acyl-CoA synthetases) are a family of enzymes that catalyze the esterification of fatty acids (FA) with CoA. Recent studies suggest that ACS enzymes drive the uptake of LCFA indirectly by their enzymatic activity and could promote special metabolic pathways dependent on their localization. The only protein located ...
Published on May 1, 2010in Journal of Lipid Research4.74
Jeffrey R. Simard8
Estimated H-index: 8
,
Tova Meshulam16
Estimated H-index: 16
+ 5 AuthorsJames A. Hamilton57
Estimated H-index: 57
Ectopic expression of caveolin-1 in HEK293 cells enhances FA sequestration in membranes as measured by a pH-sensitive fluorescent dye (1). We hypothesized that sequestration of FA is due to the enrichment of caveolin in the cytosolic leaflet and its ability to facilitate the formation of lipid rafts to buffer high FA levels. Here we show that ec­topic expression of caveolin-3 also results in enhanced FA sequestration. To further discriminate the effect that caveolins have on transmembrane FA mov...
Published on Jan 1, 2010in Physiological Reviews24.25
Jan F. C. Glatz67
Estimated H-index: 67
,
Joost J. F. P. Luiken46
Estimated H-index: 46
,
Arend Bonen75
Estimated H-index: 75
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, ...
Published on Jun 12, 2009in Journal of Biological Chemistry
James G. Nickerson4
Estimated H-index: 4
,
Hakam Alkhateeb5
Estimated H-index: 5
+ 10 AuthorsJan F. C. Glatz67
Estimated H-index: 67
In selected mammalian tissues, long chain fatty acid transporters (FABPpm, FAT/CD36, FATP1, and FATP4) are co-expressed. There is controversy as to whether they all function as membrane-bound transporters and whether they channel fatty acids to oxidation and/or esterification. Among skeletal muscles, the protein expression of FABPpm, FAT/CD36, and FATP4, but not FATP1, correlated highly with the capacities for oxidative metabolism (r ≥ 0.94), fatty acid oxidation (r ≥ 0.88), and triacylglycerol ...
Published on Mar 1, 2009in Progress in Lipid Research12.54
Isabelle Niot26
Estimated H-index: 26
(École nationale supérieure de biologie appliquée à la nutrition et à l'Alimentation),
Hélène Poirier13
Estimated H-index: 13
(École nationale supérieure de biologie appliquée à la nutrition et à l'Alimentation)
+ 1 AuthorsPhilippe Besnard36
Estimated H-index: 36
(École nationale supérieure de biologie appliquée à la nutrition et à l'Alimentation)
Over the two last decades, cloning of proteins responsible for trafficking and metabolic fate of long-chain fatty acids (LCFA) in gut has provided new insights on cellular and molecular mechanisms involved in fat absorption. To this systematic cloning period, functional genomics has succeeded in providing a new set of surprises. Disruption of several genes, thought to play a crucial role in LCFA absorption, did not lead to clear phenotypes. This observation raises the question of the real physio...
Cited By14
Newest
Published on 2019in Antioxidants
Małgorzata Zakłos-Szyda3
Estimated H-index: 3
,
Nina Pawlik1
Estimated H-index: 1
+ 3 AuthorsAnna Podsędek16
Estimated H-index: 16
In recent years, there has been increasing interest in studying food-originated phytocompounds with beneficial influences for humans. Amongst the most active natural substances are polyphenols, for which high content has been identified in the Viburnum opulus berry, and which are unused in Western Europe. Due to its strong antioxidant activity we explored the potential of V. opulus as a preventive agent against diet-related chronic diseases, such as obesity and type 2 diabetes. Among the causes ...
Published on Apr 4, 2019in Disease Markers2.76
Young Sik Kim33
Estimated H-index: 33
(KU: Korea University),
Jiyoon Jung2
Estimated H-index: 2
(KU: Korea University)
+ 4 AuthorsJung-Woo Choi12
Estimated H-index: 12
(KU: Korea University)
The increased requirement of fatty acids forces cancer cells to enhance uptake of fatty acids from the extracellular milieu, in addition to de novo lipogenesis. Coexpression of cluster of differentiation 36 (CD36) with fatty acid transport protein 4 (FATP4) or long-chain acyl CoA synthetase 1 (ACSL1) synergistically activated fatty acid uptake in experimental models. In this study, we investigated the immunohistochemical expression of CD36, FATP4, and ACSL1 in 180 cases of clear cell renal cell ...
Published on Jun 19, 2019in Growth Factors Journal1.24
Lingjie Li (BNU: Beijing Normal University), Jin Ma (BNU: Beijing Normal University)+ 2 AuthorsJing Zhang (BNU: Beijing Normal University)
Published on Jan 1, 2019in Renal Failure1.69
Yinyin Chen1
Estimated H-index: 1
(Hunan Normal University),
Liyu He11
Estimated H-index: 11
(CSU: Central South University)
+ 4 AuthorsYumei Liang3
Estimated H-index: 3
(Hunan Normal University)
AbstractBackground: Obesity has become a worldwide epidemic, and the incidence of obesity is increasing year by year. Obesity-related nephropathy (ORN) is a common kidney complication of obesity. L...
Published on Jul 1, 2018in Journal of Lipid Research4.74
Jan F. C. Glatz15
Estimated H-index: 15
(UM: Maastricht University),
Joost J. F. P. Luiken46
Estimated H-index: 46
(UM: Maastricht University)
Published on Jan 1, 2018in Animal Science Journal1.30
Masayuki Hayashi5
Estimated H-index: 5
(National Agriculture and Food Research Organization),
Kyoko Kido1
Estimated H-index: 1
(National Agriculture and Food Research Organization),
Kyoko Hodate4
Estimated H-index: 4
Vitamin A (VA) restriction in beef cattle improves meat marbling; however, the underlying molecular mechanisms remain incompletely understood. We performed microarray analysis to clarify the effect of VA restriction on Longissimus thoracis gene expressions in Japanese Black steers. Six Japanese Black steers 13–14 months of age were divided into two groups: S group (n = 3), which received VA supplementation, and R group (n = 3), in which dietary VA intake was restricted. Steers were fattened for ...
Published on Dec 1, 2017in International Journal of Obesity4.51
Etienne Lefai29
Estimated H-index: 29
,
Stéphane Blanc45
Estimated H-index: 45
+ 6 AuthorsChantal Simon48
Estimated H-index: 48
Exercise training improves fat metabolism independent of total energy expenditure in sedentary overweight men, but does not restore lean metabolic phenotype
Published on Dec 1, 2017in Scientific Reports4.01
Kanimozhi Vairamani2
Estimated H-index: 2
(University of Cincinnati Academic Health Center),
Hong-Sheng Wang38
Estimated H-index: 38
(University of Cincinnati Academic Health Center)
+ 2 AuthorsGary E. Shull72
Estimated H-index: 72
(University of Cincinnati Academic Health Center)
Loss of the AE3 Cl−/HCO3 − exchanger (Slc4a3) in mice causes an impaired cardiac force-frequency response and heart failure under some conditions but the mechanisms are not known. To better understand the functions of AE3, we performed RNA Seq analysis of AE3-null and wild-type mouse hearts and evaluated the data with respect to three hypotheses (CO2 disposal, facilitation of Na+-loading, and recovery from an alkaline load) that have been proposed for its physiological functions. Gene Ontology a...
Published on Jun 29, 2017in Frontiers in Physiology3.20
Fengfang Qiu3
Estimated H-index: 3
(CUTe: China University of Technology),
Liang Xie6
Estimated H-index: 6
+ 7 AuthorsXiquan Zhang13
Estimated H-index: 13
(SCAU: South China Agricultural University)
Intramuscular fat (IMF) is recognized as the predominant factor affecting meat quality due to its positive correlation with tenderness, juiciness and flavor. Chicken IMF deposition depends on the balance among lipid synthesis, transport, uptake and subsequent metabolism, involving a lot of genes and pathways, however, its precise molecular mechanisms remain poorly understood. In the present study, the breast muscle tissue of female Wenchang chickens (WC) (higher IMF content, 1.24 in D120 and 1.6...
Published on Jun 1, 2017in Journal of Phycology2.83
Justin Lee1
Estimated H-index: 1
(UCSD: University of California, San Diego),
Shounak Ghosh1
Estimated H-index: 1
(UCSD: University of California, San Diego),
Milton H. Saier91
Estimated H-index: 91
(UCSD: University of California, San Diego)
Galdieria sulphuraria and Cyanidioschyzon merolae are thermo-acidophilic unicellular red algal cousins capable of living in volcanic environments, although the former can additionally thrive in the presence of toxic heavy metals. Bioinformatic analyses of transport systems were carried out on their genomes, as well as that of the mesophilic multicellular red alga Chondrus crispus (Irish moss). We identified transport proteins related to the metabolic capabilities, physiological properties, and e...
View next paperOverexpression of human fatty acid transport protein 2/very long chain acyl-CoA synthetase 1 (FATP2/Acsvl1) reveals distinct patterns of trafficking of exogenous fatty acids