Regulation of the Rat SREBP-1c Promoter in Primary Rat Hepatocytes

Deng, Xiong; Cagen, Lauren M.; Wilcox, Henry G.; Park, Edwards A.; Raghow, Rajendra; Elam, Marshall B.

doi:10.1006/bbrc.2001.6148

Cited by 98 publications

(94 citation statements)

References 27 publications

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“…Sterol 12-hydroxylase (CYP8B1) is the specific enzyme for cholic acid synthesis and determines the ratio of cholic to chenodeoxicholic acid. This enzyme is known to be upregulated by SREBP1 [56] of which the promoter is inhibited by ALA in rat hepatocytes [57]. These studies suggest that our decrease in the ratio of cholic to chenodeoxicholic acid may be due to an inhibition of sterol 12-hydroxylase via SREBP1.…”

Section: Sterol Metabolismmentioning

confidence: 58%

Dose effect of alpha-linolenic acid on lipid metabolism in the hamster

Morise¹,

Mourot²,

Riottot³

et al. 2005

Reprod. Nutr. Dev.

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-In order to meet dietary requirements, the consumption of α-linolenic acid (ALA, 18:3 n-3) must be promoted. However, its effects on triglyceride (TG) and cholesterol metabolism are still controversial, and may be dose-dependent. The effects of increasing dietary ALA intakes (1%, 10%, 20% and 40% of total FA) were investigated in male hamsters. ALA replaced oleic acid while linoleic and saturated FA were kept constant. Triglyceridemia decreased by 45% in response to 10% dietary ALA and was not affected by higher intakes. It was associated with lower hepatic total activities of acetyl-CoA-carboxylase (up to -29%) and malic enzyme (up to -42%), which were negatively correlated to ALA intake (r 2 = 0.33 and r 2 = 0.38, respectively). Adipose tissue lipogenesis was 2-6 fold lower than in the liver and was not affected by dietary treatment. Substitution of 10% ALA for oleic acid increased cholesterolemia by 15% but, as in TG, higher ALA intakes did not amplify the response. The highest ALA intake (40%) dramatically modified the hepatobiliary metabolism of sterols: cholesterol content fell by 45% in the liver and increased by 28% in the faeces. Besides, faecal bile acids decreased by 61%, and contained more hydrophobic and less secondary bile acids. Thus, replacing 10% oleic acid by ALA is sufficient to exert a beneficial hypotriglyceridemic effect, which may be counteracted by the slight increase in cholesterolemia. Higher intakes did not modify these parameters, but a very high dose resulted in adverse effects on sterol metabolism. α-linolenic acid / oleic acid / lipogenesis / cholesterol / triglyceride / bile acid / hamster

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Section: Sterol Metabolismmentioning

confidence: 58%

Dose effect of alpha-linolenic acid on lipid metabolism in the hamster

Morise¹,

Mourot²,

Riottot³

et al. 2005

Reprod. Nutr. Dev.

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“…Chromatin Immunoprecipitation Assays-Rat hepatocytes were prepared as described previously (15). Chromatin immunoprecipitation assays were conducted with minor modification as described by Jurado et al (16).…”

Section: Methodsmentioning

confidence: 99%

A Thyroid Hormone Response Unit Formed between the Promoter and First Intron of the Carnitine Palmitoyltransferase-Iα Gene Mediates the Liver-specific Induction by Thyroid Hormone

Jackson‐Hayes

Song

Lavrentyev

et al. 2003

Journal of Biological Chemistry

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Carnitine palmitoyltransferase-I (CPT-I) catalyzes the rate-controlling step of fatty acid oxidation. CPT-I converts long-chain fatty acyl-CoAs to acylcarnitines for translocation across the mitochondrial membrane. The mRNA levels and enzyme activity of the liver isoform, CPT-I␣, are greatly increased in the liver of hyperthyroid animals. Thyroid hormone (T3) stimulates CPT-I␣ transcription far more robustly in the liver than in nonhepatic tissues. We have shown that the thyroid hormone receptor (TR) binds to a thyroid hormone response element (TRE) located in the CPT-I␣ promoter. In addition, elements in the first intron participate in the T3 induction of CPT-I␣ gene expression, but the CPT-I␣ intron alone cannot confer a T3 response. We found that deletion of sequences in the first intron between ؉653 and ؉744 decreased the T3 induction of CPT-I␣. Upstream stimulatory factor (USF) and CCAAT enhancer binding proteins (C/EBPs) bind to elements within this region, and these factors are required for the T3 response. The binding of TR and C/EBP to the CPT-I␣ gene in vivo was shown by the chromatin immunoprecipitation assay. We determined that TR can physically interact with USF-1, USF-2, and C/EBP␣. Transgenic mice were created that carry CPT-I␣-luciferase transgenes with or without the first intron of the CPT-I␣ gene. In these mouse lines, the first intron is required for T3 induction as well as high levels of hepatic expression. Our data indicate that the T3 stimulates CPT-I␣ gene expression in the liver through a T3 response unit consisting of the TRE in the promoter and additional factors, C/EBP and USF, bound in the first intron.

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“…Luciferase activity was corrected for both protein content and Renilla activity to account for cell density and transfection efficiency, respectively. Primary rat hepatocytes were transfected using Lipofectamine 2000 (Invitrogen) as we have done previously (28). Transfections included 1 g of CPT-I␣-luciferase and 0.1 g of TK-Renilla.…”

Section: Transient Transfection Of Luciferasementioning

confidence: 99%

Section: Transient Transfection Of Luciferasementioning

confidence: 99%

“…Rat primary hepatocytes were prepared as described previously (28). Rat primary hepatocytes (3 ϫ 10 6 in 60-mm dishes) were maintained for 12 h in priming media of RPMI 1640 and charcoal-stripped 10% fetal bovine serum (28). The cells were treated with 100 nM T3 for 24 h. Cross-linking was performed with 1% formaldehyde for 15 min at room temperature and stopped by adding 125 mM glycine to each plate for 5 min.…”

Section: Transient Transfection Of Luciferasementioning

confidence: 99%

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Peroxisomal Proliferator-activated Receptor-γ Coactivator-1α (PGC-1α) Enhances the Thyroid Hormone Induction of Carnitine Palmitoyltransferase I (CPT-Iα)

Zhang

Song

et al. 2004

Journal of Biological Chemistry

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Carnitine palmitoyltransferase I (CPT-I) catalyzes the rate-controlling step in the pathway of mitochondrial fatty acid oxidation. Thyroid hormone will stimulate the expression of the liver isoform of CPT-I (CPT-I␣). This induction of CPT-I␣ gene expression requires the thyroid hormone response element in the promoter and sequences within the first intron. The peroxisomal proliferator-activated receptor-␥ coactivator-1␣ (PGC-1␣) is a coactivator that promotes mitochondrial biogenesis, mitochondrial fatty acid oxidation, and hepatic gluconeogenesis. In addition, PGC-1␣ will stimulate the expression of CPT-I␣ in primary rat hepatocytes. Here we report that thyroid hormone will increase PGC-1␣ mRNA and protein levels in rat hepatocytes. In addition, overexpression of PGC-1␣ will enhance the thyroid hormone induction of CPT-I␣ indicating that PGC-1␣ is a coactivator for thyroid hormone. By using chromatin immunoprecipitation assays, we show that PGC-1␣ is associated with both the thyroid hormone response element in the CPT-I␣ gene promoter and the first intron of the CPT-I␣ gene. Our data demonstrate that PGC-1␣ participates in the stimulation of CPT-I␣ gene expression by thyroid hormone and suggest that PGC-1␣ is a coactivator for thyroid hormone.

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Regulation of the Rat SREBP-1c Promoter in Primary Rat Hepatocytes

Cited by 98 publications

References 27 publications

Dose effect of alpha-linolenic acid on lipid metabolism in the hamster

Dose effect of alpha-linolenic acid on lipid metabolism in the hamster

A Thyroid Hormone Response Unit Formed between the Promoter and First Intron of the Carnitine Palmitoyltransferase-Iα Gene Mediates the Liver-specific Induction by Thyroid Hormone

Peroxisomal Proliferator-activated Receptor-γ Coactivator-1α (PGC-1α) Enhances the Thyroid Hormone Induction of Carnitine Palmitoyltransferase I (CPT-Iα)

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