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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 mRNA expression of genes relating to lipid and cholesterol metabolism.mRNA expression of genes associated with fatty acid oxidation and transport (A) and cholesterol metabolism (B) from liver tissue of HCLD and HFLD fed mice were checked by quantitative real-time PCR. Values are mean ±standard error of the mean (SEM), n = 12 each group. Actin was used as controls, 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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f4: Relative mRNA expression of genes relating to lipid and cholesterol metabolism.mRNA expression of genes associated with fatty acid oxidation and transport (A) and cholesterol metabolism (B) from liver tissue of HCLD and HFLD fed mice were checked by quantitative real-time PCR. Values are mean ±standard error of the mean (SEM), n = 12 each group. Actin was used as controls, t-test was performed to detect the difference between two groups.*indicated the significant difference between two groups, P < 0.05.

Mentions: Comparing to HFLD feeding, HCLD feeding (1) induced much higher expression of lipogenesis related proteins SCD1 and ACC (Fig. 3A). We examined both mRNA and protein levels of t-ACC and did not find any differences between the two groups; (2) significantly decreased expressions of miR-122 (61% decrease), miR-370 (64% decrease) and miR-33 (70% decrease), which involved in the regulation of lipid metabolism (Fig. 3B); 3) down-regulated the mRNA expression of genes related to fatty acid oxidation, such as carnitine palmytotransferase 1 (Cpt1α), peroxisome proliferator-activated receptor alpha (Pparα) and peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (Pgc1α) (Fig. 4A); (4) resulted in higher mRNA expression of liver X receptor α (Lxrα) and fatty acid translocase (Fat/Cd36) (Fig. 4A); and 5) decreased mRNA expression of cholesterol efflux genes ATP-binding cassette sub-family G member 5 (Abcg5) and ATP-binding cassette sub-family G member 8 (Abcg8), and bile acid synthesis genes ATP-binding cassette sub-family G member 11 (Abcg11), cytochrome P450 (CYP)7A1(Cyp7a1) and Cyp8b1 (Fig. 4B).


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 mRNA expression of genes relating to lipid and cholesterol metabolism.mRNA expression of genes associated with fatty acid oxidation and transport (A) and cholesterol metabolism (B) from liver tissue of HCLD and HFLD fed mice were checked by quantitative real-time PCR. Values are mean ±standard error of the mean (SEM), n = 12 each group. Actin was used as controls, 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

f4: Relative mRNA expression of genes relating to lipid and cholesterol metabolism.mRNA expression of genes associated with fatty acid oxidation and transport (A) and cholesterol metabolism (B) from liver tissue of HCLD and HFLD fed mice were checked by quantitative real-time PCR. Values are mean ±standard error of the mean (SEM), n = 12 each group. Actin was used as controls, t-test was performed to detect the difference between two groups.*indicated the significant difference between two groups, P < 0.05.
Mentions: Comparing to HFLD feeding, HCLD feeding (1) induced much higher expression of lipogenesis related proteins SCD1 and ACC (Fig. 3A). We examined both mRNA and protein levels of t-ACC and did not find any differences between the two groups; (2) significantly decreased expressions of miR-122 (61% decrease), miR-370 (64% decrease) and miR-33 (70% decrease), which involved in the regulation of lipid metabolism (Fig. 3B); 3) down-regulated the mRNA expression of genes related to fatty acid oxidation, such as carnitine palmytotransferase 1 (Cpt1α), peroxisome proliferator-activated receptor alpha (Pparα) and peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (Pgc1α) (Fig. 4A); (4) resulted in higher mRNA expression of liver X receptor α (Lxrα) and fatty acid translocase (Fat/Cd36) (Fig. 4A); and 5) decreased mRNA expression of cholesterol efflux genes ATP-binding cassette sub-family G member 5 (Abcg5) and ATP-binding cassette sub-family G member 8 (Abcg8), and bile acid synthesis genes ATP-binding cassette sub-family G member 11 (Abcg11), cytochrome P450 (CYP)7A1(Cyp7a1) and Cyp8b1 (Fig. 4B).

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