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Vitamin A and feeding statuses modulate the insulin-regulated gene expression in Zucker lean and fatty primary rat hepatocytes.

Chen W, Howell ML, Li Y, Li R, Chen G - PLoS ONE (2014)

Bottom Line: Unattended hepatic insulin resistance predisposes individuals to dyslipidemia, type 2 diabetes and many other metabolic complications.To examine the effects of vitamin A (VA), total energy intake and feeding conditions on the insulin-regulated gene expression in primary hepatocytes of Zucker lean (ZL) and fatty (ZF) rats, we analyze the expression levels of hepatic model genes in response to the treatments of insulin and retinoic acid (RA).These results demonstrate that VA and feeding statuses modulate the hepatic insulin sensitivity at the gene expression level.

View Article: PubMed Central - PubMed

Affiliation: Department of Nutrition, University of Tennessee at Knoxville, Knoxville, Tennessee, United States of America.

ABSTRACT
Unattended hepatic insulin resistance predisposes individuals to dyslipidemia, type 2 diabetes and many other metabolic complications. The mechanism of hepatic insulin resistance at the gene expression level remains unrevealed. To examine the effects of vitamin A (VA), total energy intake and feeding conditions on the insulin-regulated gene expression in primary hepatocytes of Zucker lean (ZL) and fatty (ZF) rats, we analyze the expression levels of hepatic model genes in response to the treatments of insulin and retinoic acid (RA). We report that the insulin- and RA-regulated glucokinase, sterol regulatory element-binding protein-1c and cytosolic form of phosphoenolpyruvate carboxykinase expressions are impaired in hepatocytes of ZF rats fed chow or a VA sufficient (VAS) diet ad libitum. The impairments are partially corrected when ZF rats are fed a VA deficient (VAD) diet ad libitum or pair-fed a VAS diet to the intake of their VAD counterparts in non-fasting conditions. Interestingly in the pair-fed ZL and ZF rats, transient overeating on the last day of pair-feeding regimen changes the expression levels of some VA catabolic genes, and impairs the insulin- and RA-regulated gene expression in hepatocytes. These results demonstrate that VA and feeding statuses modulate the hepatic insulin sensitivity at the gene expression level.

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Differential expression levels of vitamin A metabolic genes in ZL and ZF primary hepatocytes.The expression levels of Rbpr2 (A), Rdh2 (B), Raldh1 (C), Raldh4 (D), Cyp26a1 (E), and Rarb (F) were determined by real-time PCR in the cultured primary hepatocytes receiving no treatment. The data were expressed as −ΔCt (36B4 - gene of interest). All p<0.05; *, #, and $ for comparing the effects of dietary manipulation variables on gene transcript levels using two-way ANOVA with Bonferroni's post-hoc test; a>b, and c>d, using Student's t-test to compare ZL with ZF with the corresponding dietary manipulation.
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pone-0100868-g008: Differential expression levels of vitamin A metabolic genes in ZL and ZF primary hepatocytes.The expression levels of Rbpr2 (A), Rdh2 (B), Raldh1 (C), Raldh4 (D), Cyp26a1 (E), and Rarb (F) were determined by real-time PCR in the cultured primary hepatocytes receiving no treatment. The data were expressed as −ΔCt (36B4 - gene of interest). All p<0.05; *, #, and $ for comparing the effects of dietary manipulation variables on gene transcript levels using two-way ANOVA with Bonferroni's post-hoc test; a>b, and c>d, using Student's t-test to compare ZL with ZF with the corresponding dietary manipulation.

Mentions: To understand the impact of transient overeating on the hepatic VA metabolism, we analyzed the expression levels of key enzymes for VA metabolism and RA responses in all three groups of ZL and ZF hepatocytes. As shown in Figure 8A, the expression level of RBP4 receptor 2 (Rbpr2), a proposed liver-specific retinol transporter [17], was higher in VAD-AD hepatocytes than that in VAS-PF-AD and VAS-PF-4M hepatocytes (both ZL and ZF). RDH2 catalyzes the reversible conversion between retinol and retinal [18]. In Figure 8A, the expression level of Rdh2 in VAD-AD ZL or ZF hepatocytes was higher than that in VAS-PF-4M ZL or ZF hepatocytes, respectively. The expression level of Rdh2 in VAS-PF-AD ZL hepatocytes was higher than that in VAS-PF-4M, but lower than that in VAD-AD ZL hepatocytes.


Vitamin A and feeding statuses modulate the insulin-regulated gene expression in Zucker lean and fatty primary rat hepatocytes.

Chen W, Howell ML, Li Y, Li R, Chen G - PLoS ONE (2014)

Differential expression levels of vitamin A metabolic genes in ZL and ZF primary hepatocytes.The expression levels of Rbpr2 (A), Rdh2 (B), Raldh1 (C), Raldh4 (D), Cyp26a1 (E), and Rarb (F) were determined by real-time PCR in the cultured primary hepatocytes receiving no treatment. The data were expressed as −ΔCt (36B4 - gene of interest). All p<0.05; *, #, and $ for comparing the effects of dietary manipulation variables on gene transcript levels using two-way ANOVA with Bonferroni's post-hoc test; a>b, and c>d, using Student's t-test to compare ZL with ZF with the corresponding dietary manipulation.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4126667&req=5

pone-0100868-g008: Differential expression levels of vitamin A metabolic genes in ZL and ZF primary hepatocytes.The expression levels of Rbpr2 (A), Rdh2 (B), Raldh1 (C), Raldh4 (D), Cyp26a1 (E), and Rarb (F) were determined by real-time PCR in the cultured primary hepatocytes receiving no treatment. The data were expressed as −ΔCt (36B4 - gene of interest). All p<0.05; *, #, and $ for comparing the effects of dietary manipulation variables on gene transcript levels using two-way ANOVA with Bonferroni's post-hoc test; a>b, and c>d, using Student's t-test to compare ZL with ZF with the corresponding dietary manipulation.
Mentions: To understand the impact of transient overeating on the hepatic VA metabolism, we analyzed the expression levels of key enzymes for VA metabolism and RA responses in all three groups of ZL and ZF hepatocytes. As shown in Figure 8A, the expression level of RBP4 receptor 2 (Rbpr2), a proposed liver-specific retinol transporter [17], was higher in VAD-AD hepatocytes than that in VAS-PF-AD and VAS-PF-4M hepatocytes (both ZL and ZF). RDH2 catalyzes the reversible conversion between retinol and retinal [18]. In Figure 8A, the expression level of Rdh2 in VAD-AD ZL or ZF hepatocytes was higher than that in VAS-PF-4M ZL or ZF hepatocytes, respectively. The expression level of Rdh2 in VAS-PF-AD ZL hepatocytes was higher than that in VAS-PF-4M, but lower than that in VAD-AD ZL hepatocytes.

Bottom Line: Unattended hepatic insulin resistance predisposes individuals to dyslipidemia, type 2 diabetes and many other metabolic complications.To examine the effects of vitamin A (VA), total energy intake and feeding conditions on the insulin-regulated gene expression in primary hepatocytes of Zucker lean (ZL) and fatty (ZF) rats, we analyze the expression levels of hepatic model genes in response to the treatments of insulin and retinoic acid (RA).These results demonstrate that VA and feeding statuses modulate the hepatic insulin sensitivity at the gene expression level.

View Article: PubMed Central - PubMed

Affiliation: Department of Nutrition, University of Tennessee at Knoxville, Knoxville, Tennessee, United States of America.

ABSTRACT
Unattended hepatic insulin resistance predisposes individuals to dyslipidemia, type 2 diabetes and many other metabolic complications. The mechanism of hepatic insulin resistance at the gene expression level remains unrevealed. To examine the effects of vitamin A (VA), total energy intake and feeding conditions on the insulin-regulated gene expression in primary hepatocytes of Zucker lean (ZL) and fatty (ZF) rats, we analyze the expression levels of hepatic model genes in response to the treatments of insulin and retinoic acid (RA). We report that the insulin- and RA-regulated glucokinase, sterol regulatory element-binding protein-1c and cytosolic form of phosphoenolpyruvate carboxykinase expressions are impaired in hepatocytes of ZF rats fed chow or a VA sufficient (VAS) diet ad libitum. The impairments are partially corrected when ZF rats are fed a VA deficient (VAD) diet ad libitum or pair-fed a VAS diet to the intake of their VAD counterparts in non-fasting conditions. Interestingly in the pair-fed ZL and ZF rats, transient overeating on the last day of pair-feeding regimen changes the expression levels of some VA catabolic genes, and impairs the insulin- and RA-regulated gene expression in hepatocytes. These results demonstrate that VA and feeding statuses modulate the hepatic insulin sensitivity at the gene expression level.

Show MeSH
Related in: MedlinePlus