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Isocaloric Pair-Fed High-Carbohydrate Diet Induced More Hepatic Steatosis and Inflammation than High-Fat Diet Mediated by miR-34a/SIRT1 Axis in Mice.

Li X, Lian F, Liu C, Hu KQ, Wang XD - Sci Rep (2015)

Bottom Line: To investigate the different effects of isocaloric high-fat diet (HFD) and high-carbohydrate diet (HCD) on hepatic steatosis and the underlying mechanisms, especially the role of microRNA-34a/silent information regulator T1 (SIRT1) axis, C57BL/6J mice (n = 12/group) were isocaloric pair-fed with Lieber-DeCarli liquid diet containing either high fat (HFLD) or high carbohydrate (HCLD) for 16 weeks.As compared to the HFLD fed mice, despite the similar final body weights, HCLD feeding: (1) induced more severe hepatic steatosis; (2) up-regulated hepatic expression of miR-34a accompanied with significant decrease of SIRT1 and nicotinamide phosphoribosyltransferase (NAMPT), SIRT1 activity and phosphorylation of AMPK; (3) up-regulated de novo lipogenesis (DNL) related proteins expression (ACC, SCD1), and down-regulated expressions of miR-122, miR-370 and miR-33; (4) decreased mRNA expressions of genes Cpt1, Pparα and Pgc1α related to fatty acid oxidation; (5) increased hepatic total cholesterol concentration and decreased expression of cholesterol metabolism related genes Abcg5, Abcg8, Abcg11, Cyp7a1 and Cyp8b1; and (6) induced higher hepatic inflammatory response accompanied with significant increased mRNA expressions of Il1β, Tnfα and Mcp1.Thus, isocaloric HCLD feeding induced greater severity in hepatic steatosis and inflammatory response than HFLD feeding, potentially through miR-34a/SIRT1 axis mediated promotion of DNL, inhibition of fatty acid oxidation and cholesterol metabolism.

View Article: PubMed Central - PubMed

Affiliation: Nutrition and Cancer Biology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA, 02111.

ABSTRACT
To investigate the different effects of isocaloric high-fat diet (HFD) and high-carbohydrate diet (HCD) on hepatic steatosis and the underlying mechanisms, especially the role of microRNA-34a/silent information regulator T1 (SIRT1) axis, C57BL/6J mice (n = 12/group) were isocaloric pair-fed with Lieber-DeCarli liquid diet containing either high fat (HFLD) or high carbohydrate (HCLD) for 16 weeks. As compared to the HFLD fed mice, despite the similar final body weights, HCLD feeding: (1) induced more severe hepatic steatosis; (2) up-regulated hepatic expression of miR-34a accompanied with significant decrease of SIRT1 and nicotinamide phosphoribosyltransferase (NAMPT), SIRT1 activity and phosphorylation of AMPK; (3) up-regulated de novo lipogenesis (DNL) related proteins expression (ACC, SCD1), and down-regulated expressions of miR-122, miR-370 and miR-33; (4) decreased mRNA expressions of genes Cpt1, Pparα and Pgc1α related to fatty acid oxidation; (5) increased hepatic total cholesterol concentration and decreased expression of cholesterol metabolism related genes Abcg5, Abcg8, Abcg11, Cyp7a1 and Cyp8b1; and (6) induced higher hepatic inflammatory response accompanied with significant increased mRNA expressions of Il1β, Tnfα and Mcp1. Thus, isocaloric HCLD feeding induced greater severity in hepatic steatosis and inflammatory response than HFLD feeding, potentially through miR-34a/SIRT1 axis mediated promotion of DNL, inhibition of fatty acid oxidation and cholesterol metabolism.

No MeSH data available.


Related in: MedlinePlus

Relative expression of hepatic miR-34a, mRNA and protein levels of NAMPT and SIRT1, and proteins level of Ac-FOXO1 and AMPK.(A) Hepatic miR-34a was quantified by real-time quantitative PCR. U6 was used as controls; (B–D) mRNA and protein expression of SIRT1 NAMPT and SIRT1, and proteins level of Ac-FOXO1 and AMPK in liver tissue were determined by real-time quantitative PCR(mRNA level) and western blot (protein expression) respectively. Actin or GAPDH was used as controls. Values expressed as mean ± standard error of the mean (SEM), n = 12 for each group except for the determination of FOXO1 and AMPK, and sample number is 7 and 6 for HCLD group and HFLD respectively. t-test was performed to detect the difference between two groups. *indicated the significant difference between two groups, P < 0.05.
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f2: Relative expression of hepatic miR-34a, mRNA and protein levels of NAMPT and SIRT1, and proteins level of Ac-FOXO1 and AMPK.(A) Hepatic miR-34a was quantified by real-time quantitative PCR. U6 was used as controls; (B–D) mRNA and protein expression of SIRT1 NAMPT and SIRT1, and proteins level of Ac-FOXO1 and AMPK in liver tissue were determined by real-time quantitative PCR(mRNA level) and western blot (protein expression) respectively. Actin or GAPDH was used as controls. Values expressed as mean ± standard error of the mean (SEM), n = 12 for each group except for the determination of FOXO1 and AMPK, and sample number is 7 and 6 for HCLD group and HFLD respectively. t-test was performed to detect the difference between two groups. *indicated the significant difference between two groups, P < 0.05.

Mentions: As compared with HFLD feeding, HCLD feeding induced significantly higher expression of miR-34a in the livers (Fig. 2A). Since miR-34a binds to the 3′UTR of Sirt1 mRNA and inhibits SIRT1 protein translation in liver3335,we found that the levels of SIRT1 at both mRNA and protein were decreased in the livers of the mice treated with HCLD (Fig. 2B1,B2) indicating an inverse association between miR-34a and SIRT1 mRNA and protein levels. Meanwhile, we also detected the decreased mRNA expression and protein levels of Nampt in HCLD fed mice in contrast to HFLD fed mice (Fig. 2C1,C2). HCLD feeding decreased hepatic phospho-adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) levels (Fig. 2D1) as compared with that of HFLD fed group, which has been shown to be positively correlated with the protein level and activity of SIRT136. Furthermore, HCLD feeding increased protein expression of acetylated fork head box protein O1 (FOXO1), the target of SIRT1 mediated deacetylation (Fig. 2D2), indicating the decreased activity of SIRT1.


Isocaloric Pair-Fed High-Carbohydrate Diet Induced More Hepatic Steatosis and Inflammation than High-Fat Diet Mediated by miR-34a/SIRT1 Axis in Mice.

Li X, Lian F, Liu C, Hu KQ, Wang XD - Sci Rep (2015)

Relative expression of hepatic miR-34a, mRNA and protein levels of NAMPT and SIRT1, and proteins level of Ac-FOXO1 and AMPK.(A) Hepatic miR-34a was quantified by real-time quantitative PCR. U6 was used as controls; (B–D) mRNA and protein expression of SIRT1 NAMPT and SIRT1, and proteins level of Ac-FOXO1 and AMPK in liver tissue were determined by real-time quantitative PCR(mRNA level) and western blot (protein expression) respectively. Actin or GAPDH was used as controls. Values expressed as mean ± standard error of the mean (SEM), n = 12 for each group except for the determination of FOXO1 and AMPK, and sample number is 7 and 6 for HCLD group and HFLD respectively. t-test was performed to detect the difference between two groups. *indicated the significant difference between two groups, P < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4660435&req=5

f2: Relative expression of hepatic miR-34a, mRNA and protein levels of NAMPT and SIRT1, and proteins level of Ac-FOXO1 and AMPK.(A) Hepatic miR-34a was quantified by real-time quantitative PCR. U6 was used as controls; (B–D) mRNA and protein expression of SIRT1 NAMPT and SIRT1, and proteins level of Ac-FOXO1 and AMPK in liver tissue were determined by real-time quantitative PCR(mRNA level) and western blot (protein expression) respectively. Actin or GAPDH was used as controls. Values expressed as mean ± standard error of the mean (SEM), n = 12 for each group except for the determination of FOXO1 and AMPK, and sample number is 7 and 6 for HCLD group and HFLD respectively. t-test was performed to detect the difference between two groups. *indicated the significant difference between two groups, P < 0.05.
Mentions: As compared with HFLD feeding, HCLD feeding induced significantly higher expression of miR-34a in the livers (Fig. 2A). Since miR-34a binds to the 3′UTR of Sirt1 mRNA and inhibits SIRT1 protein translation in liver3335,we found that the levels of SIRT1 at both mRNA and protein were decreased in the livers of the mice treated with HCLD (Fig. 2B1,B2) indicating an inverse association between miR-34a and SIRT1 mRNA and protein levels. Meanwhile, we also detected the decreased mRNA expression and protein levels of Nampt in HCLD fed mice in contrast to HFLD fed mice (Fig. 2C1,C2). HCLD feeding decreased hepatic phospho-adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) levels (Fig. 2D1) as compared with that of HFLD fed group, which has been shown to be positively correlated with the protein level and activity of SIRT136. Furthermore, HCLD feeding increased protein expression of acetylated fork head box protein O1 (FOXO1), the target of SIRT1 mediated deacetylation (Fig. 2D2), indicating the decreased activity of SIRT1.

Bottom Line: To investigate the different effects of isocaloric high-fat diet (HFD) and high-carbohydrate diet (HCD) on hepatic steatosis and the underlying mechanisms, especially the role of microRNA-34a/silent information regulator T1 (SIRT1) axis, C57BL/6J mice (n = 12/group) were isocaloric pair-fed with Lieber-DeCarli liquid diet containing either high fat (HFLD) or high carbohydrate (HCLD) for 16 weeks.As compared to the HFLD fed mice, despite the similar final body weights, HCLD feeding: (1) induced more severe hepatic steatosis; (2) up-regulated hepatic expression of miR-34a accompanied with significant decrease of SIRT1 and nicotinamide phosphoribosyltransferase (NAMPT), SIRT1 activity and phosphorylation of AMPK; (3) up-regulated de novo lipogenesis (DNL) related proteins expression (ACC, SCD1), and down-regulated expressions of miR-122, miR-370 and miR-33; (4) decreased mRNA expressions of genes Cpt1, Pparα and Pgc1α related to fatty acid oxidation; (5) increased hepatic total cholesterol concentration and decreased expression of cholesterol metabolism related genes Abcg5, Abcg8, Abcg11, Cyp7a1 and Cyp8b1; and (6) induced higher hepatic inflammatory response accompanied with significant increased mRNA expressions of Il1β, Tnfα and Mcp1.Thus, isocaloric HCLD feeding induced greater severity in hepatic steatosis and inflammatory response than HFLD feeding, potentially through miR-34a/SIRT1 axis mediated promotion of DNL, inhibition of fatty acid oxidation and cholesterol metabolism.

View Article: PubMed Central - PubMed

Affiliation: Nutrition and Cancer Biology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA, 02111.

ABSTRACT
To investigate the different effects of isocaloric high-fat diet (HFD) and high-carbohydrate diet (HCD) on hepatic steatosis and the underlying mechanisms, especially the role of microRNA-34a/silent information regulator T1 (SIRT1) axis, C57BL/6J mice (n = 12/group) were isocaloric pair-fed with Lieber-DeCarli liquid diet containing either high fat (HFLD) or high carbohydrate (HCLD) for 16 weeks. As compared to the HFLD fed mice, despite the similar final body weights, HCLD feeding: (1) induced more severe hepatic steatosis; (2) up-regulated hepatic expression of miR-34a accompanied with significant decrease of SIRT1 and nicotinamide phosphoribosyltransferase (NAMPT), SIRT1 activity and phosphorylation of AMPK; (3) up-regulated de novo lipogenesis (DNL) related proteins expression (ACC, SCD1), and down-regulated expressions of miR-122, miR-370 and miR-33; (4) decreased mRNA expressions of genes Cpt1, Pparα and Pgc1α related to fatty acid oxidation; (5) increased hepatic total cholesterol concentration and decreased expression of cholesterol metabolism related genes Abcg5, Abcg8, Abcg11, Cyp7a1 and Cyp8b1; and (6) induced higher hepatic inflammatory response accompanied with significant increased mRNA expressions of Il1β, Tnfα and Mcp1. Thus, isocaloric HCLD feeding induced greater severity in hepatic steatosis and inflammatory response than HFLD feeding, potentially through miR-34a/SIRT1 axis mediated promotion of DNL, inhibition of fatty acid oxidation and cholesterol metabolism.

No MeSH data available.


Related in: MedlinePlus