Protein expression of fatty acid transporter 2 is polarized to the trophoblast basal plasma membrane and increased in placentas from overweight/obese women

AbstractContextPlacental transport capacity influences fetal glucose supply. The syncytiotrophoblast is the transporting epithelium in the human placenta, expressing glucose transporters (GLUTs) and insulin receptors (IRs) in its maternal-facing microvillous plasma membrane (MVM) and fetal-facing basal plasma membrane (BM).ObjectiveThe objectives of this study were to (i) determine the expression of the insulin-sensitive GLUT4 glucose transporter and IR in the syncytiotrophoblast plasma membranes across gestation in normal pregnancy and in pregnancies complicated by maternal obesity, and (ii) assess the effect of insulin on GLUT4 plasma membrane trafficking in human placental explants.Design, Setting, and ParticipantsPlacental tissue was collected across gestation from women with normal body mass index (BMI) and mothers with obesity with appropriate for gestational age and macrosomic infants. MVM and BM were isolated.Main Outcome MeasuresProtein expression of GLUT4, GLUT1, and IR were determined by western blot.ResultsGLUT4 was exclusively expressed in the BM, and IR was predominantly expressed in the MVM, with increasing expression across gestation. BM GLUT1 expression was increased and BM GLUT4 expression was decreased in women with obesity delivering macrosomic babies. In placental villous explants, incubation with insulin stimulated Akt (S473) phosphorylation (+76%, P = 0.0003, n = 13) independent of maternal BMI and increased BM GLUT4 protein expression (+77%, P = 0.0013, n = 7) in placentas from lean women but not women with obesity.ConclusionWe propose that maternal insulin stimulates placental glucose transport by promoting GLUT4 trafficking to the BM, which may enhance glucose transfer to the fetus in response to postprandial hyperinsulinemia in women with normal BMI.

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Skeletal muscle fatty acid transporter protein expression in type 2 diabetes patients compared with overweight, sedentary men and age-matched, endurance-trained cyclists

Acta Physiologica ◽

10.1111/j.1748-1716.2007.01698.x ◽

2007 ◽

Vol 190 (3) ◽

pp. 209-219 ◽

Cited By ~ 18

Author(s):

M. M. A. L. Pelsers ◽

K. Tsintzas ◽

H. Boon ◽

K. Jewell ◽

L. Norton ◽

...

Keyword(s):

Type 2 Diabetes ◽

Skeletal Muscle ◽

Fatty Acid ◽

Protein Expression ◽

Transporter Protein ◽

Fatty Acid Transporter ◽

Acid Transporter ◽

Diabetes Patients

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

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00419.2001 ◽

2002 ◽

Vol 282 (2) ◽

pp. E491-E495 ◽

Cited By ~ 139

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.

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Fatty acid transporter expression is decreased in placental macrovascular endothelial cells, but not trophoblasts, in obese women

Placenta ◽

10.1016/j.placenta.2016.06.245 ◽

2016 ◽

Vol 45 ◽

pp. 132

Author(s):

Xiaohua Yang ◽

Patricia Glazebrook ◽

Maricela Haghiac ◽

Judi Minium ◽

Sylvie Hauguel deMouzon ◽

...

Keyword(s):

Endothelial Cells ◽

Fatty Acid ◽

Obese Women ◽

Fatty Acid Transporter ◽

Acid Transporter ◽

Transporter Expression

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Changes in fatty acid transport and transporters are related to the severity of insulin deficiency

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00011.2002 ◽

2002 ◽

Vol 283 (3) ◽

pp. E612-E621 ◽

Cited By ~ 75

Author(s):

Joost J. F. P. Luiken ◽

Yoga Arumugam ◽

Rhonda C. Bell ◽

Jorge Calles-Escandon ◽

Narendra N. Tandon ◽

...

Keyword(s):

Skeletal Muscle ◽

Adipose Tissue ◽

Plasma Membrane ◽

Fatty Acid ◽

Fatty Acid Transport ◽

Acid Uptake ◽

Acid Transport ◽

Fatty Acid Binding ◽

Fatty Acid Transporter ◽

Acid Transporter

We have examined the effects of streptozotocin (STZ)-induced diabetes (moderate and severe) on fatty acid transport and fatty acid transporter (FAT/CD36) and plasma membrane-bound fatty acid binding protein (FABPpm) expression, at the mRNA and protein level, as well as their plasmalemmal localization. These studies have shown that, with STZ-induced diabetes, 1) fatty acid transport across the plasma membrane is increased in heart, skeletal muscle, and adipose tissue and is reduced in liver; 2) changes in fatty acid transport are generally not associated with changes in fatty acid transporter mRNAs, except in the heart; 3) increases in fatty acid transport in heart and skeletal muscle occurred with concomitant increases in plasma membrane FAT/CD36, whereas in contrast, the increase and decrease in fatty acid transport in adipose tissue and liver, respectively, were accompanied by concomitant increments and reductions in plasma membrane FABPpm; and finally, 4) the increases in plasma membrane transporters (FAT/CD36 in heart and skeletal muscle; FABPpm in adipose tissue) were attributable to their increased expression, whereas in liver, the reduced plasma membrane FABPpm appeared to be due to its relocation within the cell in the face of slightly increased expression. Taken together, STZ-induced changes in fatty acid uptake demonstrate a complex and tissue-specific pattern, involving different fatty acid transporters in different tissues, in combination with different underlying mechanisms to alter their surface abundance.

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Glucose transport across the basal plasma membrane of human placental syncytiotrophoblast

Biochimica et Biophysica Acta (BBA) - Biomembranes ◽

10.1016/0005-2736(85)90472-9 ◽

1985 ◽

Vol 815 (1) ◽

pp. 44-50 ◽

Cited By ~ 48

Author(s):

Larry W. Johnson ◽

Carl H. Smith

Keyword(s):

Plasma Membrane ◽

Glucose Transport ◽

Basal Plasma Membrane ◽

Basal Plasma

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Initiation of HeLa cell adhesion to collagen is dependent upon collagen receptor upregulation, segregation to the basal plasma membrane, clustering and binding to the cytoskeleton

Journal of Cell Science ◽

10.1242/jcs.101.4.873 ◽

1992 ◽

Vol 101 (4) ◽

pp. 873-883

Author(s):

M.L. Lu ◽

R.J. McCarron ◽

B.S. Jacobson

Keyword(s):

Plasma Membrane ◽

Cell Attachment ◽

Cell Spreading ◽

Threshold Effect ◽

Type I ◽

Receptor Clustering ◽

Collagen Receptors ◽

Basal Plasma Membrane ◽

Basal Plasma ◽

Collagen Receptor

It was recently reported that HeLa cells have three Arg-Gly-Asp-dependent collagen receptors that do not appear to be in the integrin family of extracellular matrix receptors and bind to either type I or IV collagen or to type I gelatin. It was our goal to determine how these receptors function in HeLa cell-substratum adhesion. We report here that the sequence of events by which the receptors mediate adhesion to collagen or gelatin is: (1) induction of cell attachment by specific collagen receptor-substratum interactions with culture dishes covalently coated with either type I collagen or gelatin - attachment is inhibited by soluble gelatin; (2) stabilization of attachment by exocytotic upregulation of the receptors to the basal plasma membrane, which was demonstrated by analyzing, during cell adhesion, the redistribution of the collagen receptors among the apical plasma membrane exposed to the culture medium, the basal plasma membrane contacting the culture dish, and an intracellular pool of plasma membrane vesicles; (3) the initiation of cell spreading by receptor clustering and cytoskeletal association. Cell spreading is a threshold effect with regard to the surface concentration of gelatin, indicating that collagen receptor clustering is a precondition to the onset of spreading. Observations consistent with this interpretation of the threshold effect are that cells attach but spread more slowly on a substratum that retards receptor clustering, and that collagen receptors, when viewed by immunofluorescence microscopy, form a punctate pattern of fluorescence in the basal plasma membrane during cell spreading. It is also shown that more collagen receptors co-isolate with nondenaturing detergent-stable cytoskeletal preparations after the collagen receptors have been either clustered by antibodies or gelatin in solution, or by a collagen matrix. This indicates that clustering drives the receptors to bind to the cytoskeleton and is a necessary step in the transition from cell attachment to cell spreading.

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