Induction of peroxisomal β-oxidation in rat liver by high-fat diets

Neat, C E; Thomassen, Magny S.; Osmundsen, Harald

doi:10.1042/bj1860369

Cited by 222 publications

(95 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The specific activity of catalase and urate oxidase in control peroxisomes increased 35.2-fold and 44.7-fold respectively, in comparison with the activity in whole homogenate. It is known that the relative amount of catalase and urate oxidase molecules in peroxisomes is reduced under the action of clofibrate [34]. This can explain the observed decrease in specific activity of these enzymes in the peroxisomal fraction from clofibrate-treated animals, with a parallel increase in the recovery of peroxisomal protein.…”

Section: Induction and Subcellular Distribution Of Rat Liver Aldehydesupporting

confidence: 53%

Intraparticulate localization and some properties of a clofibrate-induced peroxisomal aldehyde dehydrogenase from rat liver

Antonenkov¹,

Pirozhkov²,

Панченко³

1985

Eur J Biochem

View full text Add to dashboard Cite

A study was made of the effect of chronic administration of the hypolipidemic drug clofibrate on the activity and intracellular localization of rat liver aldehyde dehydrogenase. The enzyme was assayed using several aliphatic and aromatic aldehydes. Clofibrate treatment caused a 1.5 to 2.3-fold increase in the liver specific aldehyde dehydrogenase activity. The induced enzyme has a high K , for acetaldehyde and was found to be located in peroxisomes and microsomes. Clofibrate did not alter the enzyme activity in the cytoplasmic fraction.The total peroxisomal aldehyde dehydrogenase activity increased 3 to 4-fold under the action of clofibrate. Disruption of the purified peroxisomes by the hypotonic treatment or in the alkaline conditions resulted in the release of catalase from the broken organelles, while aldehyde dehydrogenase as well as nucleoid-bound urate oxidase and the peroxisomal membrane marker NADH : cytochrome c reductase remained in the peroxisomal 'ghosts'. At the same time, treatment by Triton X-100 led to solubilization of the membrane-bound NADH : cytochrome c reductase and aldehyde dehydrogenase from intact peroxisomes and their 'ghosts'. These results indicate that aldehyde dehydrogenase is located in the peroxisomal membrane.The peroxisomal aldehyde dehydrogenase is active with different aliphatic and aromatic aldehydes, except for formaldehyde and glyceraldehyde. The enzyme K, values lie in the millimolar range for acetaldehyde, propionaldehyde, benzaldehyde and phenylacetaldehyde and in the micromolar range for nonanal. Both NAD and NADP serve as coenzymes for the enzyme. Aldehyde dehydrogenase was inhibited by disulfiram, Nethylmaleimide and 5,5'-dithiobis(2-nitrobenzoic)acid. According to its basic kinetic properties peroxisomal aldehyde dehydrogenase seems to be similar to a clofibrate-induced microsomal enzyme. The functional role of both enzymes in the liver cells is discussed.There are two isoenzymes of aldehyde dehydrogenase in rat liver which differ in their subcellular distribution, kinetic and molecular properties. Isoenzyme with a low K, for acetaldehyde was found in the mitochondria1 matrix [I, 21. Another species of aldehyde dehydrogenase has a high K,,, for acetaldehyde. The latter isoenzyme is tightly membranebound and distributed among mitochondria and microsomes [l, 3, 41. Except for these organelles, the activity of aldehyde dehydrogenase was detected in peroxisomes [5, 61. However, its intraparticulate location and properties were not described.Some xenobiotics and chemical carcinogens are able to induce at least two new isoenzymes of aldehyde dehydrogenase which are localized in supernatant fraction and not detectable in normal liver [7-lo]. In rat hepatomas the specific cytosolic isoenzymes which preferentially oxidize aromatic aldehydes using NADP as coenzyme are found [lo -121. All these isoenzymes consistently differ in a number of kinetic and molecular properties from aldehyde dehydrogenase of normal liver.It is known that clofibrate and other hypolipidemic agents with...

show abstract

Section: Induction and Subcellular Distribution Of Rat Liver Aldehydesupporting

confidence: 53%

Intraparticulate localization and some properties of a clofibrate-induced peroxisomal aldehyde dehydrogenase from rat liver

Antonenkov¹,

Pirozhkov²,

Панченко³

1985

Eur J Biochem

View full text Add to dashboard Cite

show abstract

“…This again would appear to be due to MEHP (or a metabolite) mimicking a natural fatty acid, in this case acting as inducer rather than as allosteric regulator. Interestingly, a similar, though much smaller, induction of peroxisomal enzymes is found in rats fed a high fat diet (61,62) and there is also marked induction in rats treated with CPUC (ethyl-2[5(4-chloro-phenyl)pentyl]oxiran-2-carboxylate) (63), valproic acid (64), or with citral (65) compounds which resemble a fatty acid but with a blocking group which will prevent ,B-oxidation. This is consistent with the proposal by Masters and Crane (66) that medium-length fatty acids (< C14) play a principal role in regulating peroxisomal lipid metabolism.…”

Section: Development Of Hepatic Changesmentioning

confidence: 61%

Effects of phthalic acid esters on the liver and thyroid.

Hinton¹,

Mitchell²,

Mann³

et al. 1986

Environ Health Perspect

127

View full text Add to dashboard Cite

The effects, over periods from 3 days to 9 months of administration, of diets containing di-2-ethylhexyl phthalate are very similar to those observed in rats administered diets containing hypolipidemic drugs such as clofibrate. Changes occur in a characteristic order commencing with alterations in the distribution of lipid within the liver, quickly followed by proliferation of hepatic peroxisomes and induction of the specialized P450 isoenzyme(s) catalyzing w oxidation of fatty acids. There follows a phase of mild liver damage indicated by induction of glucose-6-phosphatase activity and a loss of glycogen, eventually leading to the formation of enlarged lysosomes through autophagy and the accumulation of lipofuscin. Associated changes are found in the kidney and thyroid. The renal changes are limited to the proximal convoluted tubules and are generally similar to changes found in the liver. The effects on the thyroid are more marked. Although the levels of thyroxine in plasma fall to about half normal values, serum triiodothyronine remains close to normal values while the appearance of the thyroid varies, very marked hyperactivity being noted 7 days after commencement of treatment, this is less marked at 14 days, but even after 9 months treatment there is clear cut evidence for hyperactivity with colloid changes which indicate this has persisted for some time. Straight chain analogs of di-2-ethylhexyl phthalate, di-n-hexyl phthalate and di-n-oxtyl phthalate differ entirely in their short-term effects on the liver and kidney but have similar effects on the thyroid.The short-term in vivo hepatic effects of the three phthalate esters can be reproduced in hepatocytes in tissue culture. All three phthalate esters, as well as clofibrate, have early marked effects on the metabolism of fatty acids in isolated hepatocytes. The nature of these changes is such as to increase storage of lipid in the liver. A hypothesis is presented to explain the progress from these initial metabolic effects to the final formation of liver tumors.

show abstract

“…Three lines of evidence suggest that PPAR␣ might be involved in PUFA control of lipogenic gene expression: (a) feeding rats high fat diets induces peroxisomal enzymes (37)(38)(39)(40), (b) in vitro transfection studies show that fatty acids activate PPAR␣ (12, 20, 21, 24, 26, 28, 34 -37), and (c) the potent peroxisome proliferator, WY14643, suppressed both mRNA S14 level and S14CAT activity in cultured primary rat hepatocytes (42). In this report, we characterize the peroxisome proliferator regulation of S14 gene transcription.…”

mentioning

confidence: 99%

Peroxisome Proliferator-activated Receptor α Inhibits Hepatic S14 Gene Transcription

Ren

Thelen

Jump

1996

Journal of Biological Chemistry

View full text Add to dashboard Cite

The peroxisome proliferator-activated receptor (PPAR␣) has been implicated in fatty acid regulation of gene transcription. Lipogenic gene transcription is inhibited by polyunsaturated fatty acids (PUFA). We have used the PUFA-sensitive rat liver S14 gene as a model to examine the role PPAR␣ plays in fatty acid regulation of hepatic lipogenic gene transcription. Both PPAR␣ and the potent peroxisome proliferator, WY14643, inhibit S14CAT activity in transfected primary hepatocytes. WY14643 and PPAR␣ target the S14 T 3 regulatory region (TRR, ؊2.8 to ؊2.5 kilobases), a region containing 3 T 3 response elements (TRE). Transfer of the TRR to the thymidine kinase (TK) promoter conferred negative control to the TKCAT gene following WY14643 and PPAR␣ treatment. Gel shift analysis showed that PPAR␣, either alone or with RXR␣, did not bind the S14TRR. However, PPAR␣ interfered with TR␤/RXR␣ binding to a TRE (DR؉4). Functional studies showed that co-transfected RXR␣, but not T 3 receptor ␤1 (TR␤1), abrogated the inhibitory effect of PPAR␣ on S14 gene transcription. These results suggest that WY14643 and PPAR␣ functionally interfere with T 3 regulation of S14 gene transcription by inhibiting TR␤1/RXR binding to S14 TREs. Previous studies had established that the cisregulatory targets of PUFA control were located within the proximal promoter region of the S14 gene, i.e. between ؊220 and ؊80 bp. Finding that the cis-regulatory elements for WY14643/PPAR␣ and PUFA are functionally and spatially distinct argues against PPAR␣ as the mediator of PUFA suppression of S14 gene transcription.

show abstract

Induction of peroxisomal β-oxidation in rat liver by high-fat diets

Cited by 222 publications

References 10 publications

Intraparticulate localization and some properties of a clofibrate-induced peroxisomal aldehyde dehydrogenase from rat liver

Intraparticulate localization and some properties of a clofibrate-induced peroxisomal aldehyde dehydrogenase from rat liver

Effects of phthalic acid esters on the liver and thyroid.

Peroxisome Proliferator-activated Receptor α Inhibits Hepatic S14 Gene Transcription

Contact Info

Product

Resources

About