Labelling of an 88 kDa adipocyte membrane protein by sulpho-N-succinimidyl long-chain fatty acids: inhibition of fatty acid transport

1992 ◽  
Vol 20 (4) ◽  
pp. 811-813 ◽  
Author(s):  
Caroll M. Harmon ◽  
Paul Luce ◽  
Nada A. Abumrad
2003 ◽  
Vol 67 (3) ◽  
pp. 454-472 ◽  
Author(s):  
Paul N. Black ◽  
Concetta C. DiRusso

SUMMARY The processes that govern the regulated transport of long-chain fatty acids across the plasma membrane are quite distinct compared to counterparts involved in the transport of hydrophilic solutes such as sugars and amino acids. These differences stem from the unique physical and chemical properties of long-chain fatty acids. To date, several distinct classes of proteins have been shown to participate in the transport of exogenous long-chain fatty acids across the membrane. More recent work is consistent with the hypothesis that in addition to the role played by proteins in this process, there is a diffusional component which must also be considered. Central to the development of this hypothesis are the appropriate experimental systems, which can be manipulated using the tools of molecular genetics. Escherichia coli and Saccharomyces cerevisiae are ideally suited as model systems to study this process in that both (i) exhibit saturable long-chain fatty acid transport at low ligand concentrations, (ii) have specific membrane-bound and membrane-associated proteins that are components of the transport apparatus, and (iii) can be easily manipulated using the tools of molecular genetics. In both systems, central players in the process of fatty acid transport are fatty acid transport proteins (FadL or Fat1p) and fatty acyl coenzyme A (CoA) synthetase (FACS; fatty acid CoA ligase [AMP forming] [EC 6.2.1.3]). FACS appears to function in concert with FadL (bacteria) or Fat1p (yeast) in the conversion of the free fatty acid to CoA thioesters concomitant with transport, thereby rendering this process unidirectional. This process of trapping transported fatty acids represents one fundamental mechanism operational in the transport of exogenous fatty acids.


2020 ◽  
Vol 295 (17) ◽  
pp. 5737-5750 ◽  
Author(s):  
Vincent M. Perez ◽  
Jeffrey Gabell ◽  
Mark Behrens ◽  
Nishikant Wase ◽  
Concetta C. DiRusso ◽  
...  

Fatty acid transport protein 2 (FATP2) is highly expressed in the liver, small intestine, and kidney, where it functions in both the transport of exogenous long-chain fatty acids and the activation of very-long-chain fatty acids. Here, using a murine model, we investigated the phenotypic impacts of deleting FATP2, followed by a transcriptomic analysis using unbiased RNA-Seq to identify concomitant changes in the liver transcriptome. WT and FATP2-null (Fatp2−/−) mice (5 weeks) were maintained on a standard chow diet for 6 weeks. The Fatp2−/− mice had reduced weight gain, lowered serum triglyceride, and increased serum cholesterol levels and attenuated dietary fatty acid absorption. Transcriptomic analysis of the liver revealed 258 differentially expressed genes in male Fatp2−/− mice and a total of 91 in female Fatp2−/− mice. These genes mapped to the following gene ontology categories: fatty acid degradation, peroxisome biogenesis, fatty acid synthesis, and retinol and arachidonic acid metabolism. Targeted RT-quantitative PCR verified the altered expression of selected genes. Of note, most of the genes with increased expression were known to be regulated by peroxisome proliferator–activated receptor α (PPARα), suggesting that FATP2 activity is linked to a PPARα-specific proximal ligand. Targeted metabolomic experiments in the Fatp2−/− liver revealed increases of total C16:0, C16:1, and C18:1 fatty acids; increases in lipoxin A4 and prostaglandin J2; and a decrease in 20-hydroxyeicosatetraenoic acid. We conclude that the expression of FATP2 in the liver broadly affects the metabolic landscape through PPARα, indicating that FATP2 provides an important role in liver lipid metabolism through its transport or activation activities.


2004 ◽  
Vol 63 (2) ◽  
pp. 259-262 ◽  
Author(s):  
Jürgen Pohl ◽  
Axel Ring ◽  
Thomas Herrmann ◽  
Wolfgang Stremmel

Efficient uptake and channelling of long-chain fatty acids (LCFA) are critical cell functions. Evidence is emerging that proteins are important mediators of LCFA-trafficking into cells and various proteins have been suggested to be involved in this process. Amongst these proteins is a family of membrane-associated proteins termed fatty acid transport proteins (FATP). So far six members of this family, designated FATP 1–6, have been characterized. FATP 1, 2 and 6 show a highly-conserved AMP-binding region that participates in the activation of very-long-chain fatty acids (VLCFA) to form their acyl-CoA derivatives. The mechanisms by which FATP mediate LCFA uptake are not well understood, but several studies provide evidence that uptake of LCFA across cellular membranes is closely linked to acyl-CoA synthetase activity. It is proposed that FATP indirectly enhance LCFA uptake by activating VLCFA to their CoA esters, which are required to maintain the typical structure of lipid rafts in cellular membranes. Recent work has shown that the structural integrity of lipid rafts is essential for cellular LCFA uptake. This effect might be exerted by proteins, e.g. caveolin-1 and FAT/CD36, that use lipid rafts as platforms and bind or transport LCFA. The proposed molecular mechanisms await further experimental investigation.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 682-682 ◽  
Author(s):  
Kayla Dillard ◽  
Morgan Coffin ◽  
Gabriella Hernandez ◽  
Victoria Smith ◽  
Catherine Johnson ◽  
...  

Abstract Objectives Non-alcoholic fatty liver disease (NAFLD) represents the major cause of pediatric chronic liver pathology in the United States. The objective of this study was to compare the relative effect of inclusion of isocaloric amounts of saturated medium-chain fatty acids (hydrogenated coconut oil), saturated long-chain fatty acids (lard) and unsaturated long-chain fatty acids (olive oil) on endpoints of NAFLD and insulin resistance. Methods Thirty-eight 15-d-old Iberian pigs were fed 1 of 4 diets containing (g/kg body weight × d) 1) control (CON; n = 8): 0 g fructose, 10.5 g fat, and 187 kcal metabolizable energy (ME), 2) lard (LAR; n = 10): 21.6 g fructose, 17.1 g fat (100% lard) and 299 kcal ME, 3) hydrogenated coconut oil (COCO; n = 10): 21.6 g fructose, 16.9 g fat (42.5% lard and 57.5% coconut oil) and 299 kcal ME, and 4) olive oil (OLV, n = 10): 21.6 g fructose, 17.1 g fat (43.5% lard and 56.5% olive oil) and 299 kcal ME, for 9 consecutive weeks. Body weight was recorded every 3 d. Serum markers of liver injury and dyslipidemia were measured on d 60 at 2 h post feeding, with all other serum measures assessed on d 70. Liver tissue was collected on d 70 for histology, triacylglyceride (TG) quantification, and metabolomics analysis. Results Tissue histology indicated the presence of steatosis in LAR, COCO and OLV compared with CON (P ≤ 0.001), with a further increase in in non-alcoholic steatohepatitis (NASH) in OLV and COCO compared with LAR (P ≤ 0.01). Alanine and aspartate aminotransferases were higher in COCO and OLV (P ≤ 0.01) than CON. All treatment groups had lower liver concentrations of methyl donor's choline and betaine versus CON, while bile acids were differentially changed (P ≤ 0.05). COCO had higher levels of TGs with less carbons (Total carbons < 52) than all other groups (P ≤ 0.05). Several long-chain acylcarnitines involved in fat oxidation were higher in OLV versus all other groups (P ≤ 0.05). Conclusions Inclusion of fats enriched in medium-chain saturated and long-chain unsaturated fatty acids in a high-fructose high-fat diet increased liver injury, compared with fats with a long-chain saturated fatty acid profile. Further research is required to investigate the mechanisms causing this difference in physiological response to these dietary fat sources. Funding Sources ARI, AcornSeekers.


1961 ◽  
Vol 200 (4) ◽  
pp. 847-850 ◽  
Author(s):  
Judith K. Patkin ◽  
E. J. Masoro

Cold acclimation is known to alter hepatic lipid metabolism. Liver slices from cold-acclimated rats have a greatly depressed capacity to synthesize long-chain fatty acids from acctate-1-C14. Since adipose tissue is the major site of lipogenic activity in the intact animal, its fatty acid synthetic capacity was studied. In contrast to the liver, it was found that adipose tissue from the cold-acclimated rat synthesized three to six times as much long-chain fatty acids per milligram of tissue protein as the adipose tissue from the control rat living at 25°C. Evidence is presented indicating that adipose tissue from cold-acclimated and control rats esterify long-chain fatty acids at the same rate. The ability of adipose tissue to oxidize palmitic acid to CO2 was found to be unaltered by cold acclimation. The fate of the large amount of fatty acid synthesized in the adipose tissue of cold-acclimated rats is discussed.


1991 ◽  
Vol 10 (3) ◽  
pp. 325-340 ◽  
Author(s):  
D. R. Webb ◽  
R. A. Sanders

Caprenin (CAP) is a triglyceride that primarily contains caprylic (C8:0), capric (C10:0), and behenic (C22:0) acids. This study was undertaken to determine whether or not CAP is qualitatively digested, absorbed, and rearranged like other dietary fats and oils that contain these medium-chain and very long-chain fatty acids. In vitro results showed that neat CAP, coconut oil (CO) and peanut oil (PO) were hydrolyzed by porcine pancreatic lipase. All of the neat triglycerides also were digested in vivo by both male and female rats. This was shown by the recovery of significantly more extractable lymphatic fat than with fat-free control animals and by the recovery of orally administered triglyceride-derived fatty acids in lymph triglycerides. However, substantially more PO (74%) and CO (51%) were recovered in lymph relative to CAP (10%). These quantitative differences are consistent with the fatty acid composition of each triglyceride and primary routes of fatty acid uptake. The 24-h lymphatic recovery of CAP-derived C8:0, C10:0, and C22:0 averaged 3.9%, 17.8%, and 11.2%, respectively, for male and female rats. The C8:0 and C10:0 results approximated those obtained with CO (2.0% and 16.3%, respectively). In contrast, the 24-h absorbability of C22:0 in CAP was significantly less than that seen in PO (55.4%). Finally, there was no evidence of significant rearrangement of the positions of fatty acids on glycerol during digestion and absorption. Those fatty acids recovered in lymphatic fat tended to occupy the same glyceride positions that they did in the neat administered oils. However, the lymph fats recovered from all animals dosed with fat emulsions were enriched with endogenous lymph fatty acids. It is concluded that CAP is qualitatively digested, absorbed, and processed like any dietary fat or oil that contains medium-chain and very long-chain fatty acids.


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