The Refsum disease marker phytanic acid, a branched chain fatty acid, affects Ca2+ homeostasis and mitochondria, and reduces cell viability in rat hippocampal astrocytes

2005 ◽  
Vol 18 (1) ◽  
pp. 110-118 ◽  
Author(s):  
Stefan Kahlert ◽  
Peter Schönfeld ◽  
Georg Reiser
Keyword(s):  
Fatty Acid ◽  
Cell Viability ◽  
Phytanic Acid ◽  
Chain Fatty Acid ◽  
Refsum Disease ◽  
Disease Marker ◽  
Branched Chain ◽  
Hippocampal Astrocytes

Effect of branched-chain fatty acid on lipid dynamics in mice lacking liver fatty acid binding protein gene

2005 ◽  
Vol 288 (3) ◽  
pp. C543-C558 ◽  
Author(s):  
Barbara P. Atshaves ◽  
Avery L. McIntosh ◽  
H. Ross Payne ◽  
John Mackie ◽  
Ann B. Kier ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Droplets ◽  
Phytanic Acid ◽  
Chain Fatty Acid ◽  
Liver Fatty Acid ◽  
Peroxisomal Enzyme ◽  
Lipid Phenotype ◽  
Gene Ablation ◽  
Branched Chain ◽  
Fabp Gene

Although a role for liver fatty acid protein (L-FABP) in the metabolism of branched-chain fatty acids has been suggested based on data obtained with cultured cells, the physiological significance of this observation remains to be demonstrated. To address this issue, the lipid phenotype and metabolism of phytanic acid, a branched-chain fatty acid, were determined in L-FABP gene-ablated mice fed a diet with and without 1% phytol (a metabolic precursor to phytanic acid). In response to dietary phytol, L-FABP gene ablation exhibited a gender-dependent lipid phenotype. Livers of phytol-fed female L-FABP−/− mice had significantly more fatty lipid droplets than male L-FABP−/− mice, whereas in phytol-fed wild-type L-FABP+/+ mice differences between males and females were not significant. Thus L-FABP gene ablation exacerbated the accumulation of lipid droplets in phytol-fed female, but not male, mice. These results were reflected in the lipid profile, where hepatic levels of triacylglycerides in phytol-fed female L-FABP−/− mice were significantly higher than in male L-FABP−/− mice. Furthermore, livers of phytol-fed female L-FABP−/− mice exhibited more necrosis than their male counterparts, consistent with the accumulation of higher levels of phytol metabolites (phytanic acid, pristanic acid) in liver and serum, in addition to increased hepatic levels of sterol carrier protein (SCP)-x, the only known peroxisomal enzyme specifically required for branched-chain fatty acid oxidation. In summary, L-FABP gene ablation exerted a significant role, especially in female mice, in branched-chain fatty acid metabolism. These effects were only partially compensated by concomitant upregulation of SCP-x in response to L-FABP gene ablation and dietary phytol.

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

2002 ◽  
Vol 283 (3) ◽  
pp. C688-C703 ◽  
Author(s):  
Barbara P. Atshaves ◽  
Stephen M. Storey ◽  
Anca Petrescu ◽  
Cynthia C. Greenberg ◽  
Olga I. Lyuksyutova ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Palmitic Acid ◽  
Lipid Accumulation ◽  
Phytanic Acid ◽  
Chain Fatty Acid ◽  
Fatty Acid Binding Proteins ◽  
Acid Oxidation ◽  
Fatty Acid Binding ◽  
Branched Chain

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.

Phytanic acid and other branched-chain fatty acid constituents of bovine rumen bacteria

1966 ◽  
Vol 33 (3) ◽  
pp. 333-342 ◽  
Author(s):  
R. P. Hansen
Keyword(s):  
Fatty Acid ◽  
Dairy Cow ◽  
Phytanic Acid ◽  
Enzymic Activity ◽  
Chain Fatty Acid ◽  
Rumen Bacteria ◽  
Grass Hay ◽  
Total Fatty Acids ◽  
Branched Chain ◽  
Perinephric Fat

SummaryPhytanic acid, 3,7,11,15-tetramethylhexadecanoic acid, which hitherto had been isolated and identified from several natural sources including butterfat, ox perinephric fat and cow plasma, has now been found present in small amounts (2·9%) in the total fatty acids extracted from the rumen bacteria of a fistulated dairy cow fed a diet of clover-grass hay. This C20 multibranched fatty acid was not detected in the dietary clover-grass hay, and it is considered to have been derived from phytol by enzymic activity of the rumen bacteria.

scholarly journals In brain mitochondria the branched-chain fatty acid phytanic acid impairs energy transduction and sensitizes for permeability transition

2004 ◽  
Vol 383 (1) ◽  
pp. 121-128 ◽  
Author(s):  
Peter SCHÖNFELD ◽  
Stefan KAHLERT ◽  
Georg REISER
Keyword(s):  
Fatty Acid ◽  
Phytanic Acid ◽  
Adenine Nucleotide ◽  
Genetic Disorder ◽  
Mitochondrial Protein ◽  
Permeability Transition ◽  
Chain Fatty Acid ◽  
The Body ◽  
Low Concentrations ◽  
Branched Chain

Phytanic acid (3,7,11,15-tetramethylhexadecanoic acid) accumulates at high levels throughout the body in the adult form of Refsum disease, a peroxisomal genetic disorder. However, it is still unclear why increased levels of phytanic acid have cytotoxic effects. In the present study, we examined the influence of non-esterified phytanic acid on energy-related functions of mitochondria from adult rat brain. Phytanic acid at low concentrations (5–20 μM, i.e. 5–20 nmol/mg of mitochondrial protein) de-energized mitochondria, as indicated by depolarization, stimulation of non-phosphorylating oxygen uptake and inhibition of the reduction of the tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide. The unbranched homologue palmitic acid exerted much smaller effects. In addition, phytanic acid reduced state 3 respiration, which was partly due to inhibition of the ADP/ATP carrier. Phytanic acid decreased the rate of adenine nucleotide exchange and increased the degree of control, which the ADP/ATP carrier has on state 3 respiration. Important for functional consequences is the finding that mitochondria, which are preloaded with small amounts of Ca2+ (100 nmol/mg of protein), became highly sensitized to rapid permeability transition even when only low concentrations of phytanic acid (below 5 μM) were applied. In conclusion, the incorporation of phytanic acid into the inner mitochondrial membrane increases the membrane H+ conductance and disturbs the protein-linked functions in energy coupling. This is most probably essential for the short-term toxicity of phytanic acid. Thus in neural tissue, which becomes enriched with phytanic acid, the reduction in mitochondrial ATP supply and the facilitation of the opening of the permeability transition pore are two major mechanisms by which the branched-chain fatty acid phytanic acid induces the onset of degenerative processes.

scholarly journals Mitochondrial and peroxisomal beta oxidation of the branched chain fatty acid 2-methylpalmitate in rat liver.

1991 ◽  
Vol 266 (36) ◽  
pp. 24670-24675 ◽  
Author(s):  
G. Vanhove ◽  
P.P. Van Veldhoven ◽  
F. Vanhoutte ◽  
G. Parmentier ◽  
H.J. Eyssen ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Rat Liver ◽  
Chain Fatty Acid ◽  
Beta Oxidation ◽  
Branched Chain
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