scholarly journals Chlorpromazine and carnitine-dependency of rat liver peroxisomal β-oxidation of long-chain fatty acids

1987 ◽  
Vol 241 (3) ◽  
pp. 783-791 ◽  
Author(s):  
J Vamecq
Keyword(s):  
Fatty Acids ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Rat Liver ◽  
Fatty Acyl ◽  
Carnitine Palmitoyltransferase ◽  
Acid Oxidation ◽  
Synthetase Activity ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Mitochondrial Fatty Acid

The enzyme targets for chlorpromazine inhibition of rat liver peroxisomal and mitochondrial oxidations of fatty acids were studied. Effects of chlorpromazine on total fatty acyl-CoA synthetase activity, on both the first and the third steps of peroxisomal beta-oxidation, on the entry of fatty acyl-CoA esters into the peroxisome and on catalase activity, which allows breakdown of the H2O2 generated during the acyl-CoA oxidase step, were analysed. On all these metabolic processes, chlorpromazine was found to have no inhibitory action. Conversely, peroxisomal carnitine octanoyltransferase activity was depressed by 0.2-1 mM-chlorpromazine, which also inhibits mitochondrial carnitine palmitoyltransferase activity in all conditions in which these enzyme reactions are assayed. Different patterns of inhibition by the drug were, however, demonstrated for both these enzyme activities. Inhibitory effects of chlorpromazine on mitochondrial cytochrome c oxidase activity were also described. Inhibitions of both cytochrome c oxidase and carnitine palmitoyltransferase are proposed to explain the decreased mitochondrial fatty acid oxidation with 0.4-1.0 mM-chlorpromazine reported by Leighton, Persico & Necochea [(1984) Biochem. Biophys. Res. Commun. 120, 505-511], whereas depression by the drug of carnitine octanoyltransferase activity is presented as the factor responsible for the decreased peroxisomal beta-oxidizing activity described by the above workers.

scholarly journals Mitochondrial Fission Governed by Drp1 Regulates Exogenous Fatty Acid Usage and Storage in Hela Cells

Metabolites ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 322
Author(s):  
Jae-Eun Song ◽  
Tiago C. Alves ◽  
Bernardo Stutz ◽  
Matija Šestan-Peša ◽  
Nicole Kilian ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Lipid Droplets ◽  
Mitochondrial Fission ◽  
Acid Oxidation ◽  
Mitochondrial Morphology ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Mitochondrial Fatty Acid ◽  
And Storage

In the presence of high abundance of exogenous fatty acids, cells either store fatty acids in lipid droplets or oxidize them in mitochondria. In this study, we aimed to explore a novel and direct role of mitochondrial fission in lipid homeostasis in HeLa cells. We observed the association between mitochondrial morphology and lipid droplet accumulation in response to high exogenous fatty acids. We inhibited mitochondrial fission by silencing dynamin-related protein 1(DRP1) and observed the shift in fatty acid storage-usage balance. Inhibition of mitochondrial fission resulted in an increase in fatty acid content of lipid droplets and a decrease in mitochondrial fatty acid oxidation. Next, we overexpressed carnitine palmitoyltransferase-1 (CPT1), a key mitochondrial protein in fatty acid oxidation, to further examine the relationship between mitochondrial fatty acid usage and mitochondrial morphology. Mitochondrial fission plays a role in distributing exogenous fatty acids. CPT1A controlled the respiratory rate of mitochondrial fatty acid oxidation but did not cause a shift in the distribution of fatty acids between mitochondria and lipid droplets. Our data reveals a novel function for mitochondrial fission in balancing exogenous fatty acids between usage and storage, assigning a role for mitochondrial dynamics in control of intracellular fuel utilization and partitioning.

scholarly journals Nrf2 affects the efficiency of mitochondrial fatty acid oxidation

2014 ◽  
Vol 457 (3) ◽  
pp. 415-424 ◽  
Author(s):  
Marthe H. R. Ludtmann ◽  
Plamena R. Angelova ◽  
Ying Zhang ◽  
Andrey Y. Abramov ◽  
Albena T. Dinkova-Kostova
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Saturated Fatty Acids ◽  
Acid Oxidation ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Atp Production ◽  
Mitochondrial Fatty Acid ◽  
Mitochondrial Oxidation ◽  
Long Chain

Transcription factor Nrf2 affects fatty acid oxidation; the mitochondrial oxidation of long-chain (palmitic) and short-chain (hexanoic) saturated fatty acids is depressed in the absence of Nrf2 and accelerated when Nrf2 is constitutively activated, affecting ATP production and FADH2 utilization.

scholarly journals Estimation of peroxisomal and mitochondrial fatty acid oxidation in rat hepatocytes using tritiated substrates

1991 ◽  
Vol 279 (1) ◽  
pp. 147-150 ◽  
Author(s):  
R Rognstad
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Specific Inhibitor ◽  
Rat Hepatocytes ◽  
Acid Oxidation ◽  
Relative Distribution ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Mitochondrial Fatty Acid

The pathways of peroxisomal and mitochondrial fatty acid oxidation were monitored with the use of substrates which produce NAD3H. I used as marker substrates: D-[3-3H]3-hydroxybutyrate for mitochondrial NAD3H production, [2-3H]glycerol for cytosolic NAD3H production, and [2-3H]acetate to measure carbon-bound 3H which was also generated by the metabolism of the commercial 9,10-3H-labelled fatty acids. The assumption that peroxisomal NAD3H can be considered to be equivalent to cytosolic NAD3H was supported using a specific inhibitor of mitochondrial fatty acid oxidation. The approach involves determination of the specific yields, and the relative distribution on carbons 4 and 6, of 3H in glucose from the marker substrates and the labelled fatty acids. In hepatocytes from clofibrate-treated rats, the amount of palmitate or oleate oxidation which starts in the peroxisomes is comparable with that which starts in the mitochondria.

3,5-Diiodo-l-thyronine rapidly enhances mitochondrial fatty acid oxidation rate and thermogenesis in rat skeletal muscle: AMP-activated protein kinase involvement

2009 ◽  
Vol 296 (3) ◽  
pp. E497-E502 ◽  
Author(s):  
A. Lombardi ◽  
P. de Lange ◽  
E. Silvestri ◽  
R. A. Busiello ◽  
A. Lanni ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Energy Metabolism ◽  
Fatty Acid Oxidation ◽  
Atp Synthesis ◽  
Acid Oxidation ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Mitochondrial Fatty Acid ◽  
Amp Activated Protein Kinase

Triiodothyronine regulates energy metabolism and thermogenesis. Among triiodothyronine derivatives, 3,5-diiodo-l-thyronine (T2) has been shown to exert marked effects on energy metabolism by acting mainly at the mitochondrial level. Here we investigated the capacity of T2 to affect both skeletal muscle mitochondrial substrate oxidation and thermogenesis within 1 h after its injection into hypothyroid rats. Administration of T2 induced an increase in mitochondrial oxidation when palmitoyl-CoA (+104%), palmitoylcarnitine (+80%), or succinate (+30%) was used as substrate, but it had no effect when pyruvate was used. T2 was able to 1) activate the AMPK-ACC-malonyl-CoA metabolic signaling pathway known to direct lipid partitioning toward oxidation and 2) increase the importing of fatty acids into the mitochondrion. These results suggest that T2 stimulates mitochondrial fatty acid oxidation by activating several metabolic pathways, such as the fatty acid import/β-oxidation cycle/FADH2-linked respiratory pathways, where fatty acids are imported. T2 also enhanced skeletal muscle mitochondrial thermogenesis by activating pathways involved in the dissipation of the proton-motive force not associated with ATP synthesis (“proton leak”), the effect being dependent on the presence of free fatty acids inside mitochondria. We conclude that skeletal muscle is a target for T2, and we propose that, by activating processes able to enhance mitochondrial fatty acid oxidation and thermogenesis, T2 could play a role in protecting skeletal muscle against excessive intramyocellular lipid storage, possibly allowing it to avoid functional disorders.

Plasma free fatty acids in mitochondrial fatty acid oxidation defects

1997 ◽  
Vol 267 (2) ◽  
pp. 143-154 ◽  
Author(s):  
G Martı́nez ◽  
G Jiménez-Sánchez ◽  
P Divry ◽  
C Vianey-Saban ◽  
E Riudor ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Free Fatty Acids ◽  
Fatty Acid Oxidation ◽  
Acid Oxidation ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Plasma Free Fatty Acids ◽  
Mitochondrial Fatty Acid

scholarly journals Specific inhibition of mitochondrial fatty acid oxidation by 2-bromopalmitate and its co-enzyme A and carnitine esters

1972 ◽  
Vol 129 (1) ◽  
pp. 55-65 ◽  
Author(s):  
J. F. A. Chase ◽  
P. K. Tubbs
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Liver Mitochondria ◽  
Carnitine Palmitoyltransferase ◽  
Acid Oxidation ◽  
Dependent Manner ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Succinate Oxidation ◽  
Mitochondrial Fatty Acid ◽  
Long Chain

1. The CoA and carnitine esters of 2-bromopalmitate are extremely powerful and specific inhibitors of mitochondrial fatty acid oxidation. 2. 2-Bromopalmitoyl-CoA, added as such or formed from 2-bromopalmitate, inhibits the carnitine-dependent oxidation of palmitate or palmitoyl-CoA, but not the oxidation of palmitoylcarnitine, by intact liver mitochondria. 3. 2-Bromopalmitoylcarnitine inhibits the oxidation of palmitoylcarnitine as well as that of palmitate or palmitoyl-CoA. It has no effect on succinate oxidation, but inhibits that of pyruvate, 2-oxoglutarate or hexanoate; however, the oxidation of these substrates (but not of palmitate, palmitoyl-CoA or palmitoyl-carnitine) is restored by carnitine. 4. In damaged mitochondria, added 2-bromopalmitoyl-CoA does inhibit palmitoylcarnitine oxidation; pyruvate oxidation is unaffected by the inhibitor alone, but is impaired if palmitoylcarnitine is subsequently added. 5. The findings have been interpreted as follows. 2-Bromopalmitoyl-CoA inactivates (in a carnitine-dependent manner) a pool of carnitine palmitoyltransferase which is accessible to external acyl-CoA. This results in inhibition of palmitate or palmitoyl-CoA oxidation. A second pool of carnitine palmitoyltransferase, inaccessible to added acyl-CoA in intact mitochondria, can generate bromopalmitoyl-CoA within the matrix from external 2-bromopalmitoylcarnitine; this reaction is reversible. Such internal 2-bromopalmitoyl-CoA inactivates long-chain β-oxidation (as does added 2-bromopalmitoyl-CoA if the mitochondria are damaged) and its formation also sequesters intramitochondrial CoA. Since this CoA is shared by pyruvate and 2-oxoglutarate dehydrogenases, the oxidation of their substrates is depressed by 2-bromopalmitoylcarnitine, unless free carnitine is available to act as a ‘sink’ for long-chain acyl groups. 6. These effects are compared with those reported for other inhibitors of fatty acid oxidation.

Regulation of leptin secretion from white adipocytes by free fatty acids

2003 ◽  
Vol 285 (3) ◽  
pp. E521-E526 ◽  
Author(s):  
Philippe G. Cammisotto ◽  
Yves Gélinas ◽  
Yves Deshaies ◽  
Ludwik J. Bukowiecki
Keyword(s):  
Fatty Acids ◽  
Chain Length ◽  
Unsaturated Fatty Acids ◽  
Saturated Fatty Acids ◽  
Acid Oxidation ◽  
Mitochondrial Fatty Acid Oxidation ◽  
White Adipocytes ◽  
Mitochondrial Fatty Acid ◽  
A Chain ◽  
Long Chain

Norepinephrine stimulates lipolysis and concurrently inhibits insulin-stimulated leptin secretion from white adipocytes. To assess whether there is a cause-effect relationship between these two metabolic events, the effects of fatty acids were investigated in isolated rat adipocytes incubated in buffer containing low (0.1%) and high (4%) albumin concentrations. Palmitic acid (1 mM) mimicked the inhibitory effects of norepinephrine (1 μM) on insulin (10 nM)-stimulated leptin secretion, but only at low albumin concentrations. Studies investigating the effects of the chain length of saturated fatty acids [from butyric (C4) to stearic (C18) acids] revealed that only fatty acids with a chain length superior or equal to eight carbons effectively inhibited insulin-stimulated leptin secretion. Long-chain mono- and polyunsaturated fatty acids constitutively present in adipocyte triglyceride stores (oleic, linoleic, γ-linolenic, palmitoleic, eicosapentanoic, and docosahexanoic acids) also completely suppressed leptin secretion. Saturated and unsaturated fatty acids inhibited insulin-stimulated leptin secretion with the same potency and without any significant effect on basal secretion. On the other hand, inhibitors of mitochondrial fatty acid oxidation (palmoxirate, 2-bromopalmitate, 2-bromocaproate) attenuated the stimulatory effects of insulin on leptin release without reversing the effects of fatty acids or norepinephrine, suggesting that fatty acids do not need to be oxidized by the mitochondria to inhibit leptin release. These results demonstrate that long-chain fatty acids mimic the effects of norepinephrine on leptin secretion and suggest that they may play a regulatory role as messengers between stimulation of lipolysis by norepinephrine and inhibition of leptin secretion.

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