PPARα agonists up-regulate organic cation transporters in rat liver cells

Luci, Sebastian; Geissler, Stefanie; König, Bettina; Koch, Alexander; Stangl, Gabriele I.; Hirche, Frank; Eder, Klaus

doi:10.1016/j.bbrc.2006.09.099

Cited by 55 publications

(51 citation statements)

References 25 publications

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“…Upregulation in the liver of the expression of this protein is expected to increase the availability of carnitine and hence stimulate mitochondrial transport of fatty acid to be oxidized in this organelle (21). In fact, we observed an increase in the hepatic carnitine concentration in rats fed a lignan preparation containing both sesamin and episesamin.…”

Section: Discussionsupporting

confidence: 54%

“…In the present study, we observed that lignans not only up-regulated the gene expression of enzymes involved in fatty acid oxidation, but also affected the expression of many genes involved in lipid and carbohydrate metabolism. The mRNA expression of appreciable numbers of these genes has also been observed to be affected in a similar fashion by various synthetic PPAR␣ agonists in the liver of experimental animals or in cultured hepatocytes (17,20,21,23,26,(32)(33)(34). Among the three lignans tested in the present study, episesamin and sesamolin were generally stronger than sesamin in altering the expression of various genes.…”

Section: Discussionmentioning

confidence: 60%

“…All the lignans significantly increased the mRNA expression of Slc22a5, which mediates highaffinity sodium-dependent carnitine transport (21). The increases were stronger with episesamin and sesamolin than with sesamin, and comparable between the two former compounds.…”

Section: Lignan-dependent Changes In Gene Expression Profiles In the mentioning

confidence: 68%

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Comparative Study of Sesame Lignans (Sesamin, Episesamin and Sesamolin) Affecting Gene Expression Profile and Fatty Acid Oxidation in Rat Liver

Ishii

Lim

Odbayar

et al. 2009

J Nutr Sci Vitaminol

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SummaryThe impact of sesamin, episesamin and sesamolin (sesame lignans) on hepatic gene expression profiles was compared with a DNA microarray. Male Sprague-Dawley rats were fed experimental diets containing 0.2% sesamin, episesamin or sesamolin, and a control diet free of lignans for 15 d. Compared to a lignan-free diet, a diet containing sesamin, episesamin and sesamolin caused 1.5-and 2-fold changes in the expression of 128 and 40, 526 and 152, and 516 and 140 genes, respectively. The lignans modified not only the mRNA levels of many enzymes involved in hepatic fatty acid oxidation, but also those of proteins involved in the transportation of fatty acids into hepatocytes and their organelles, and regulating hepatic concentrations of carnitine, CoA and malonyl-CoA. It is apparent that sesame lignans stimulate hepatic fatty acid oxidation by affecting the gene expression of various proteins regulating hepatic fatty acid metabolism. We also observed that lignans modified the gene expression of various proteins involved in hepatic lipogenesis, cholesterogenesis and glucose metabolism. The changes were generally greater with episesamin and sesamolin than with sesamin. In terms of the amounts accumulated in serum and the liver, the lignans ranked in the order sesamolin, episesamin and sesamin. The differences in bioavailability among these lignans appear to be important to their divergent physiological activities.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 60%

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Comparative Study of Sesame Lignans (Sesamin, Episesamin and Sesamolin) Affecting Gene Expression Profile and Fatty Acid Oxidation in Rat Liver

Ishii

Lim

Odbayar

et al. 2009

J Nutr Sci Vitaminol

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“…Increased expression of OCTN2 leads to an increased uptake of carnitine into the liver and this may provide an explanation for increased carnitine concentrations in the liver of rats treated with clofibrate [17] . The recent finding that feeding of an oxidized fat, which is known to activate PPAR ␣ [18][19][20] , also causes an upregulation of gene expression of OCTN2 in the liver and intestine and increases tissue carnitine concentrations confirms a role of PPAR ␣ in the gene expression of OCTN2 and carnitine homeostasis [21] .…”

mentioning

confidence: 99%

“…We have recently shown that activation of peroxisome proliferator-activated receptor (PPAR)-␣ by clofibrate, a synthetic agonist, causes an upregulation of OCTN2 in the liver of rats [17] . Increased expression of OCTN2 leads to an increased uptake of carnitine into the liver and this may provide an explanation for increased carnitine concentrations in the liver of rats treated with clofibrate [17] .…”

mentioning

confidence: 99%

Fasting and Caloric Restriction Increases mRNA Concentrations of Novel Organic Cation Transporter-2 and Carnitine Concentrations in Rat Tissues

2008

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Background: Recently, we have shown that activation of peroxisome proliferator-activated receptor (PPAR)-α by clofibrate leads to an upregulation of novel organic cation transporter (OCTN)-2, a carnitine transporter, and in turn increases the carnitine concentration in the liver of rats. In this study, we tested the hypothesis that fasting and caloric restriction, conditions under which PPARα activation also occurs, cause similar effects. Methods: Three groups of rats received the diet either ad libitum (control rats) or 10.5 g diet/day (70% of energy requirement for maintenance, E70 rats) or 6 g diet/day (40% of energy requirement for maintenance, E40 rats) for 10 days. A 4th group received the diet ad libitum for 9 days and was then fasted for 24 h (fasted rats). Results: Fasted and calorie-restricted rats had increased mRNA concentrations of acyl-CoA oxidase and carnitine palmitoyltransferase-1 in the liver, heart and kidneys compared to control rats (p < 0.05), indicative of activation of PPARα in these tissues. E70 rats had increased OCTN2 mRNA concentrations in liver (2.6-fold) and kidneys (1.5-fold) and increased total carnitine concentrations in these tissues compared to control rats. E40 rats had increased OCTN2 mRNA concentrations in the liver (3.3-fold), skeletal muscle (2.2-fold), heart (2.3-fold) and kidneys (3.5-fold) and increased total carnitine concentrations in these four tissues compared to control rats. Fasted rats had increased OCTN2 mRNA concentrations in the liver (4.0-fold), heart (2.1-fold) and kidneys (2.0-fold) and increased total carnitine concentrations in these three tissues (p < 0.05). Conclusion: The study shows that fasting and caloric restriction lead to an upregulation of OCTN2 in several tissues, probably mediated by activation of PPARα. Increased tissue carnitine concentrations in fasted and calorie-restricted rats might be at least in part due to increased uptake of carnitine by OCTN2.

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Beyond PXR and CAR, Regulation of Xenobiotic Metabolism by other Nuclear Receptors

Wagner

Zollner

Trauner

2008

Nuclear Receptors in Drug Metabolism

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PPARα agonists up-regulate organic cation transporters in rat liver cells

Cited by 55 publications

References 25 publications

Comparative Study of Sesame Lignans (Sesamin, Episesamin and Sesamolin) Affecting Gene Expression Profile and Fatty Acid Oxidation in Rat Liver

Comparative Study of Sesame Lignans (Sesamin, Episesamin and Sesamolin) Affecting Gene Expression Profile and Fatty Acid Oxidation in Rat Liver

Fasting and Caloric Restriction Increases mRNA Concentrations of Novel Organic Cation Transporter-2 and Carnitine Concentrations in Rat Tissues

Beyond PXR and CAR, Regulation of Xenobiotic Metabolism by other Nuclear Receptors

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