Expression of fatty acid binding proteins inhibits lipid accumulation and alters toxicity in L cell fibroblasts

High levels of saturated, branched-chain fatty acids are deleterious to cells and animals, resulting in lipid accumulation and cytotoxicity. Although fatty acid binding proteins (FABPs) are thought to be protective, this hypothesis has not previously been examined. Phytanic acid (branched chain, 16-carbon backbone) induced lipid accumulation in L cell fibroblasts similar to that observed with palmitic acid (unbranched, C16): triacylglycerol ≫ free fatty acid > cholesterol > cholesteryl ester ≫ phospholipid. Although expression of sterol carrier protein (SCP)-2, SCP-x, or liver FABP (L-FABP) in transfected L cells reduced [3H]phytanic acid uptake (57–87%) and lipid accumulation (21–27%), nevertheless [3H]phytanic acid oxidation was inhibited (74–100%) and phytanic acid toxicity was enhanced in the order L-FABP ≫ SCP-x > SCP-2. These effects differed markedly from those of [3H]palmitic acid, whose uptake, oxidation, and induction of lipid accumulation were not reduced by L-FABP, SCP-2, or SCP-x expression. Furthermore, these proteins did not enhance the cytotoxicity of palmitic acid. In summary, intracellular FABPs reduce lipid accumulation induced by high levels of branched-chain but not straight-chain saturated fatty acids. These beneficial effects were offset by inhibition of branched-chain fatty acid oxidation that correlated with the enhanced toxicity of high levels of branched-chain fatty acid.

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Ataxia associated with increased plasma concentrations of pristanic acid, phytanic acid and C27 bile acids but normal fibroblast branched-chain fatty acid oxidation

Journal of Inherited Metabolic Disease ◽

10.1007/bf01799170 ◽

1996 ◽

Vol 19 (6) ◽

pp. 761-768 ◽

Cited By ~ 8

Author(s):

P. T. Clayton ◽

A. W. Johnson ◽

K. A. Mills ◽

G. W. Lynes ◽

J. Wilson ◽

...

Keyword(s):

Fatty Acid ◽

Bile Acids ◽

Fatty Acid Oxidation ◽

Phytanic Acid ◽

Plasma Concentrations ◽

Chain Fatty Acid ◽

Normal Fibroblast ◽

Acid Oxidation ◽

Pristanic Acid ◽

Branched Chain

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A novel acyl-CoA-binding protein from bovine liver. Effect on fatty acid synthesis

Biochemical Journal ◽

10.1042/bj2410189 ◽

1987 ◽

Vol 241 (1) ◽

pp. 189-192 ◽

Cited By ~ 93

Author(s):

I B Mogensen ◽

H Schulenberg ◽

H O Hansen ◽

F Spener ◽

J Knudsen

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Binding Protein ◽

Fatty Acid Synthetase ◽

Bovine Liver ◽

Acid Synthesis ◽

Fatty Acid Binding Proteins ◽

Fatty Acid Binding ◽

Medium Chain ◽

Chain Acyl

Bovine liver was shown to contain a hitherto undescribed medium-chain acyl-CoA-binding protein. The protein co-purifies with fatty-acid-binding proteins, but was, unlike these proteins, unable to bind fatty acids. The protein induced synthesis of medium-chain acyl-CoA esters on incubation with goat mammary-gland fatty acid synthetase. The possible function of the protein is discussed.

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Interaction of fatty acids with recombinant rat intestinal and liver fatty acid-binding proteins

Archives of Biochemistry and Biophysics ◽

10.1016/0003-9861(91)90044-j ◽

1991 ◽

Vol 286 (1) ◽

pp. 300-309 ◽

Cited By ~ 90

Author(s):

Gyorgy Nemecz ◽

Timothy Hubbell ◽

John R. Jefferson ◽

John B. Lowe ◽

Friedhelm Schroeder

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Binding Proteins ◽

Fatty Acid Binding Proteins ◽

Liver Fatty Acid ◽

Fatty Acid Binding

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Fatty acid binding proteins have the potential to channel dietary fatty acids into enterocyte nuclei

The Journal of Lipid Research ◽

10.1194/jlr.m062232 ◽

2015 ◽

Vol 57 (2) ◽

pp. 219-232 ◽

Cited By ~ 17

Author(s):

Adriana Esteves ◽

Anja Knoll-Gellida ◽

Lucia Canclini ◽

Maria Cecilia Silvarrey ◽

Michèle André ◽

...

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Binding Proteins ◽

Dietary Fatty Acids ◽

Fatty Acid Binding Proteins ◽

Fatty Acid Binding

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Properties of Acetate Kinase Isozymes and a Branched-Chain Fatty Acid Kinase from a Spirochete

Journal of Bacteriology ◽

10.1128/jb.152.1.246-254.1982 ◽

1982 ◽

Vol 152 (1) ◽

pp. 246-254

Author(s):

Caroline S. Harwood ◽

Ercole Canale-Parola

Keyword(s):

Amino Acids ◽

Fatty Acids ◽

Molecular Weight ◽

Fatty Acid ◽

Branched Chain Amino Acids ◽

Chain Fatty Acid ◽

Acetate Kinase ◽

Nucleoside Triphosphate ◽

Branched Chain ◽

Chain Fatty Acids

Spirochete MA-2, which is anaerobic, ferments glucose, forming acetate as a major product. The spirochete also ferments (but does not utilize as growth substrates) small amounts of l -leucine, l -isoleucine, and l -valine, forming the branched-chain fatty acids isovalerate, 2-methylbutyrate, and isobutyrate, respectively, as end products. Energy generated through the fermentation of these amino acids is utilized to prolong cell survival under conditions of growth substrate starvation. A branched-chain fatty acid kinase and two acetate kinase isozymes were resolved from spirochete MA-2 cell extracts. Kinase activity was followed by measuring the formation of acyl phosphate from fatty acid and ATP. The branched-chain fatty acid kinase was active with isobutyrate, 2-methylbutyrate, isovalerate, butyrate, valerate, or propionate as a substrate but not with acetate as a substrate. The acetate kinase isozymes were active with acetate and propionate as substrates but not with longer-chain fatty acids as substrates. The acetate kinase isozymes and the branched-chain fatty acid kinase differed in nucleoside triphosphate and cation specificities. Each acetate kinase isozyme had an apparent molecular weight of approximately 125,000, whereas the branched-chain fatty acid kinase had a molecular weight of approximately 76,000. These results show that spirochete MA-2 synthesizes a branched-chain fatty acid kinase specific for leucine, isoleucine, and valine fermentation. It is likely that a phosphate branched-chain amino acids is also synthesized by spirochete MA-2. Thus, in spirochete MA-2, physiological mechanisms have evolved which serve specifically to generate maintenance energy from branched-chain amino acids.

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Omega-3 fatty acids transport through the placenta

Asian Journal of Medical and Biological Research ◽

10.3329/ajmbr.v2i1.27561 ◽

2016 ◽

Vol 2 (1) ◽

pp. 1-8

Author(s):

Ariful Islam ◽

Takanori Kodama ◽

Yui Yamamoto ◽

Majid Ebrahimi ◽

Hirofumi Miyazaki ◽

...

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Placental Transfer ◽

Fatty Acid Binding Proteins ◽

Fatty Acid Transport ◽

Omega 3 ◽

Fatty Acid Binding ◽

Membrane Bound ◽

Fatty Acid Transport Proteins

The placenta is a temporary vital organ for sustaining the development of the fetus throughout gestation. Although the fatty acid composition delivered to the fetus is largely determined by maternal circulating levels, the placenta preferentially transfers physiologically important long-chain polyunsaturated fatty acids (LC-PUFAs), particularly omega-3 (n-3) FAs. The precise mechanisms governing these transfers were covered in a veil, but have started to be revealed gradually. Several evidences suggest fatty acid transport proteins (FATPs), placental specific membrane bound fatty acid binding proteins (pFABPpm) and fatty acid translocases (FAT/CD36) involved in LC-PUFAs uptake. Our studies have shown that the placental transfer of omega-3 FAs through the trophoblast cells is largely contributed by fatty acid binding protein 3 (FABP3). Recently there are considerable interests in the potential for dietary omega-3 FAs as a therapeutic intervention for fetal disorders. In fact, prenatal supply of omega-3 FAs is essential for brain and retinal development. Recent findings suggest a potential opportunity of omega-3 FA interventions to decrease the incidence of type 2 diabetes in future generations. In this review, we discuss the molecular mechanism of transportation of omega-3 FAs through the placenta and how omega-3 FAs deficiency/supplementation impact on fetal development.Asian J. Med. Biol. Res. March 2016, 2(1): 1-8

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Enterocyte fatty acid uptake and intestinal fatty acid-binding protein

Biochemical Society Transactions ◽

10.1042/bst0320075 ◽

2004 ◽

Vol 32 (1) ◽

pp. 75-78 ◽

Cited By ~ 42

Author(s):

P. Tso ◽

A. Nauli ◽

C.-M. Lo

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Fatty Acid Binding Protein ◽

Brush Border Membrane ◽

Fatty Acid Uptake ◽

Current Understanding ◽

Fatty Acid Binding Proteins ◽

Acid Uptake ◽

Micellar Solubilization ◽

Fatty Acid Binding

This article reviews our current understanding of the uptake of fatty acids by the enterocytes of the intestine. The micellar solubilization of fatty acids by bile salts and the factors regulating that process are discussed. The mechanism of how micellar solubilization of fatty acids promotes the uptake of fatty acids by enterocytes and their relative importance is reviewed. Additionally, discussion of the various fatty acid transporters located at the brush border membrane of the enterocytes is included. Finally, a summary of our current understanding of the function of fatty-acid-binding proteins inside enterocytes is provided.

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