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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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Related in: MedlinePlus

VAS-PF-AD ZL and ZF overate on the last day when sufficient VAS diet was provided.(A) The schematic graph of the setup for the pair-feeding regimen. VAD ad libitum (VAD-AD, n = 5), VAS pair-feeding last day ad libitum (VAS-PF-AD, n = 5), VAS pair-feeding last day 4 meals (VAS-PF-4M, n = 5) (B) Tail tip whole blood glucose from ZL and ZF rats before sacrifice. Each circle represents a value from an individual animal. The bars represent mean ± S.E.M. * Indicates p<0.05 using one-way ANOVA with LSD post-hoc test. (C) The accumulative food intake for ZL and ZF rats over 56 days of pair-feeding regimen. (D) The food intake and (E) body mass change for ZL and ZF rats on day 56 of the pair-feeding regimen. * Indicates p<0.05 using one-way ANOVA with LSD post-hoc test.
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pone-0100868-g003: VAS-PF-AD ZL and ZF overate on the last day when sufficient VAS diet was provided.(A) The schematic graph of the setup for the pair-feeding regimen. VAD ad libitum (VAD-AD, n = 5), VAS pair-feeding last day ad libitum (VAS-PF-AD, n = 5), VAS pair-feeding last day 4 meals (VAS-PF-4M, n = 5) (B) Tail tip whole blood glucose from ZL and ZF rats before sacrifice. Each circle represents a value from an individual animal. The bars represent mean ± S.E.M. * Indicates p<0.05 using one-way ANOVA with LSD post-hoc test. (C) The accumulative food intake for ZL and ZF rats over 56 days of pair-feeding regimen. (D) The food intake and (E) body mass change for ZL and ZF rats on day 56 of the pair-feeding regimen. * Indicates p<0.05 using one-way ANOVA with LSD post-hoc test.

Mentions: Rats fed a VAD diet after weaning reduced food intakes at around 5 weeks [13]. To determine how total and acute food intakes affect the insulin-regulated hepatic gene expression, an 8-week pair-feeding experiment was designed. Rats were divided into three groups, VAD-AD, VAS-PF-AD and VAS-PF-4M (Figure 3A, see Materials and Methods for detail). Figure 3B shows that VAS-PF-AD ZL and ZF rats ingested 54% and 112% more food on the last day than VAD-AD ZL and ZF rats did, respectively, demonstrating the overeating of VAS-PF-AD rats. The overeating of VAS-PF-AD rats did not significantly increase the total caloric intake over the entire pair-feeding period compared to VAD-AD and VAS-PF-4M counterparts (Figure 3C). Correspondingly, VAS-PF-AD ZL and ZF rats gained 4% and 6% of body mass on the last day, respectively (Figure 3D). Before sacrifice, the tail tip whole blood glucose levels of VAS-PF-AD ZF rats were significantly higher than those of VAD-AD and VAS-PF-4M rats (Figure 3E).


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)

VAS-PF-AD ZL and ZF overate on the last day when sufficient VAS diet was provided.(A) The schematic graph of the setup for the pair-feeding regimen. VAD ad libitum (VAD-AD, n = 5), VAS pair-feeding last day ad libitum (VAS-PF-AD, n = 5), VAS pair-feeding last day 4 meals (VAS-PF-4M, n = 5) (B) Tail tip whole blood glucose from ZL and ZF rats before sacrifice. Each circle represents a value from an individual animal. The bars represent mean ± S.E.M. * Indicates p<0.05 using one-way ANOVA with LSD post-hoc test. (C) The accumulative food intake for ZL and ZF rats over 56 days of pair-feeding regimen. (D) The food intake and (E) body mass change for ZL and ZF rats on day 56 of the pair-feeding regimen. * Indicates p<0.05 using one-way ANOVA with LSD post-hoc test.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0100868-g003: VAS-PF-AD ZL and ZF overate on the last day when sufficient VAS diet was provided.(A) The schematic graph of the setup for the pair-feeding regimen. VAD ad libitum (VAD-AD, n = 5), VAS pair-feeding last day ad libitum (VAS-PF-AD, n = 5), VAS pair-feeding last day 4 meals (VAS-PF-4M, n = 5) (B) Tail tip whole blood glucose from ZL and ZF rats before sacrifice. Each circle represents a value from an individual animal. The bars represent mean ± S.E.M. * Indicates p<0.05 using one-way ANOVA with LSD post-hoc test. (C) The accumulative food intake for ZL and ZF rats over 56 days of pair-feeding regimen. (D) The food intake and (E) body mass change for ZL and ZF rats on day 56 of the pair-feeding regimen. * Indicates p<0.05 using one-way ANOVA with LSD post-hoc test.
Mentions: Rats fed a VAD diet after weaning reduced food intakes at around 5 weeks [13]. To determine how total and acute food intakes affect the insulin-regulated hepatic gene expression, an 8-week pair-feeding experiment was designed. Rats were divided into three groups, VAD-AD, VAS-PF-AD and VAS-PF-4M (Figure 3A, see Materials and Methods for detail). Figure 3B shows that VAS-PF-AD ZL and ZF rats ingested 54% and 112% more food on the last day than VAD-AD ZL and ZF rats did, respectively, demonstrating the overeating of VAS-PF-AD rats. The overeating of VAS-PF-AD rats did not significantly increase the total caloric intake over the entire pair-feeding period compared to VAD-AD and VAS-PF-4M counterparts (Figure 3C). Correspondingly, VAS-PF-AD ZL and ZF rats gained 4% and 6% of body mass on the last day, respectively (Figure 3D). Before sacrifice, the tail tip whole blood glucose levels of VAS-PF-AD ZF rats were significantly higher than those of VAD-AD and VAS-PF-4M rats (Figure 3E).

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