Microsomal Δ9, Δ6 and Δ5 desaturase activities and liver membrane fatty acid profiles in alcohol‐fed rats

Venkatesan, S.; Rideout, J.M.; Simpson, Kenneth J.

doi:10.1002/bmc.1130040605

Cited by 16 publications

(9 citation statements)

References 43 publications

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“…However, although ACAT activity was decreased, GPAT activity was increased, and DGAT activity tended to increase (P 5 0.06) after tamoxifen treatment, no change was seen in the mRNA level of SCD-1. Tamoxifen did not fully induce fatty liver in this experiment, but we found that tamoxifen treatment decreased the 20:5n-3/18:3n-3 and 20:4n-6/ 18:2n-6 ratios, as has been reported in severe fatty liver induced by ethanol, obesity, or the hyperlipidemic drug tridecylthiopropanoic acid (13,29,30). These changes in fatty acids ratios suggested that the activities of the desaturases involved in the biosynthesis of long-chain polyunsaturated fatty acids were decreased, although no changes were seen in the gene expressions of D6 and D5 desaturases.…”

Section: Discussionsupporting

confidence: 68%

Causes and prevention of tamoxifen-induced accumulation of triacylglycerol in rat liver

Gudbrandsen¹,

Røst²,

Berge

2006

Journal of Lipid Research

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Tamoxifen can induce hepatic steatosis in women. In this study, we wanted to elucidate the mechanism behind the tamoxifen-induced accumulation of triacylglycerol in liver in female rats, and we hoped to prevent this development by combination treatment with the modified fatty acid tetradecylthioacetic acid (TTA). The increased hepatic triacylglycerol level after tamoxifen treatment was accompanied by decreased acetyl-coenzyme A carboxylase (ACC) and FAS activities, increased glycerol-3-phosphate acyltransferase (GPAT) activity, and a tendency to increased diacylglycerol acyltransferase (DGAT) activity. The activities and mRNA levels of enzymes involved in b-oxidation, ketogenesis, and uptake of lipids from liver were unaffected by tamoxifen, whereas the uptake of lipoproteins was unchanged and the uptake of fatty acids was decreased. Combination treatment with tamoxifen and TTA (Tam1TTA) normalized the hepatic triacylglycerol level and increased the activities of ACC, FAS, GPAT, and DGAT compared with tamoxifentreated rats. The activities and mRNA levels of enzymes involved in b-oxidation, ketogenesis, and uptake of lipids were increased after Tam1TTA treatment. In conclusion, tamoxifen increased the hepatic triacylglycerol level, probably as a result of increased triacylglycerol biosynthesis combined with unchanged b-oxidation. The tamoxifen-induced accumulation of triacylglycerol was prevented by cotreatment with TTA, through mechanisms of increased mitochondrial and peroxisomal b-oxidation. The anti-estrogen agent tamoxifen has been used as an effective treatment for estrogen receptor-positive breast cancers for several years (1). However, tamoxifen treatment is associated with an increased risk of developing fatty liver (steatosis) (2-4), and it is reported that as many as 43% of women with breast cancer treated with tamoxifen may develop steatosis within the first 2 years of treatment (4). It has been hypothesized that impaired fatty acid b-oxidation could be the cause of fatty liver after tamoxifen treatment (5, 6).The modified fatty acid tetradecylthioacetic acid (TTA) is a ligand for all peroxisome proliferator-activated receptors (PPARs) (7) and has shown promise in the prevention and treatment of common lipid disorders and insulin resistance (8). TTA increases both mitochondrial and peroxisomal b-oxidation in liver (9) and therefore may be a valuable tool for the treatment of fatty liver.In this study, female rats with 7,12-dimethylbenz[a]anthracene-induced mammary tumors were treated with tamoxifen, TTA, or a combination of tamoxifen and TTA (Tam1TTA) for 14 days after palpable tumors developed. We had two aims in this study: first, we wanted to elucidate the mechanism behind the accumulation of triacylglycerol in liver after tamoxifen treatment in this rat model; second, we wanted to investigate whether cotreatment with TTA could abolish this undesirable side effect of tamoxifen. To clarify the mechanisms involved, we measured the activities and gene expression of enzymes controlling the hep...

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Section: Discussionsupporting

confidence: 68%

Causes and prevention of tamoxifen-induced accumulation of triacylglycerol in rat liver

Gudbrandsen¹,

Røst²,

Berge

2006

Journal of Lipid Research

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“…On the other hand, reports of the effect of ethanol on the microsomal electron transport system have been contradictory ( 13,15,16). Another study with rats reported no ethanol effect on A6 desaturase activity (17), although this study may have been confounded by essential fatty acid deficiency.…”

Section: Introductionmentioning

confidence: 66%

Selective reduction of delta 6 and delta 5 desaturase activities but not delta 9 desaturase in micropigs chronically fed ethanol.

Nakamura¹,

Tang²,

Villanueva³

et al. 1994

J. Clin. Invest.

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This study investigated the mechanism by which chronic ethanol feeding reduces arachidonate and other highly unsaturated fatty acids in pig liver phospholipids. Five micropigs were fed a diet providing 89 kcal/kg body wt for 12 mo, with ethanol and fat as 40 and 34% ofenergy, respectively. Five control pigs were pairfed corn starch instead of ethanol. The activities of A6 and A5 desaturases (expressed as microsomal conversion of precursor to product) in liver from ethanol-fed pigs were reduced to less than half that of controls, whereas the activity of A9 desaturase was unaffected in the ethanol group. A5 Desaturase activity showed positive correlation with the abundance of its products in liver total phospholipids and microsomes in the ethanol group, but not in the controls. Correlation between A6 desaturase activity and its products showed similar pattern to that of A5 desaturase, but did not reach statistical significance. No difference was observed between the two groups in coenzyme A concentration in the liver. These results suggest that the selective reduction of A6 and A5 desaturase activities, not the microsomal electron transport system, are directly responsible for the altered profile of liver phospholipids. (J. Clin. Invest. 1994. 93:450-454.) Key words: pig -arachidonic acidessential fatty acids * alcoholic liver disease

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“…Our findings show that ethanol does not act uniformly across desaturase systems. Venkatesan et al (1990) showed that ⌬5 desaturase activity, but not ⌬6 desaturase activity, was decreased in alcohol-fed rats. We showed that ⌬5 desaturase was overall more sensitive to ethanol than ⌬6 desaturase.…”

Section: Discussionmentioning

confidence: 97%

“…In vitro studies have shown decreased liver ⌬6 and ⌬5 desaturase activities; these enzymes are the limiting steps of PUFA synthesis (Buko et al, 1988;Umeki et al, 1984;Wang et al, 1983). Other studies suggest that ethanol does not act uniformly across desaturase systems (Nakamura et al, 1994;Venkatesan et al, 1990) or even increase these enzyme activities (Pawlosky and Salem, 1999). The amount of alcohol consumed and the duration of the ingestion could partly explain these discrepancies.…”

mentioning

confidence: 92%

Effect of Ethanol on Polyunsaturated Fatty Acid Biosynthesis in Hepatocytes From Spontaneously Hypertensive Rats

Narce

Poisson

Bellenger

et al. 2001

Alcoholism Clin & Exp Res

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Our study showed that hepatocyte PUFA biogenesis is dependent on ethanol concentration. Ethanol strongly inhibits the synthesis of PUFA in hepatocytes from SHR, which can explain the deficit of prostaglandin precursors observed in cardiovascular diseases linked to ethanol intoxication. n-3 PUFA supplemented diet reinforces the inhibition of arachidonic acid synthesis, likely by a substrate competition toward Delta5 desaturation. This in vitro approach provides a better understanding of the effects of ethanol on fatty acid metabolism in relation to hypertension.

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Microsomal Δ⁹, Δ⁶ and Δ⁵ desaturase activities and liver membrane fatty acid profiles in alcohol‐fed rats

Cited by 16 publications

References 43 publications

Causes and prevention of tamoxifen-induced accumulation of triacylglycerol in rat liver

Causes and prevention of tamoxifen-induced accumulation of triacylglycerol in rat liver

Selective reduction of delta 6 and delta 5 desaturase activities but not delta 9 desaturase in micropigs chronically fed ethanol.

Effect of Ethanol on Polyunsaturated Fatty Acid Biosynthesis in Hepatocytes From Spontaneously Hypertensive Rats

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