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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

Proposed mechanisms of HCD induced liver injury in mice.High carbohydrate diet feeding upregualted the expression of miR-34a,which could inhibited the protein expression and activity of NAMPT, SIRT1 and AMPK, then increased the expression of genes related to hepatic inflammatory response, hepatic de novo lipogenesis and cholesterol deposition, decreased the expression of genes involved in fatty acid oxidation in the livers, thus, the enhanced hepatic inflammation, steatosis and cholesterol deposition synergesticlly resulted in the liver injury.
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f6: Proposed mechanisms of HCD induced liver injury in mice.High carbohydrate diet feeding upregualted the expression of miR-34a,which could inhibited the protein expression and activity of NAMPT, SIRT1 and AMPK, then increased the expression of genes related to hepatic inflammatory response, hepatic de novo lipogenesis and cholesterol deposition, decreased the expression of genes involved in fatty acid oxidation in the livers, thus, the enhanced hepatic inflammation, steatosis and cholesterol deposition synergesticlly resulted in the liver injury.

Mentions: In the present study, despite similar energy intake and final body weight by group pair-feeding with the liquid diet, HCLD feeding for 16 weeks significantly increased the liver weight and the ratio of liver weight/body weight, and induced more severity of hepatic steatosis and cholesterol deposition than HFLD feeding. These changes were accompanied with significantly increased DNL related markers (SCD1 and ACC), and decreased mRNA level of genes related to fatty acid oxidation and cholesterol metabolism (Fig. 6). Although the difference in hepatic TG concentrations between HCLD and HFLD feeding mice did not reach statistical significance, this could be due to the fact that the distribution of steatosis in the liver is local, combined with the small portion of liver tissue used for biochemical analysis. We believe that the steatosis grading determined by histopathologic analysis for 20 random fields of the liver tissue section provided more reliable evidence for the hepatic lipid deposition. Meanwhile, HCLD feeding resulted in much higher incidence of hepatic inflammatory response accompanying with the increased expression of pro-inflammatory cytokines. Taken together, the present study provided strong experimental evidence that HCLD feeding, as compared with HFLD feeding, induced more detrimental effects in the liver.


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)

Proposed mechanisms of HCD induced liver injury in mice.High carbohydrate diet feeding upregualted the expression of miR-34a,which could inhibited the protein expression and activity of NAMPT, SIRT1 and AMPK, then increased the expression of genes related to hepatic inflammatory response, hepatic de novo lipogenesis and cholesterol deposition, decreased the expression of genes involved in fatty acid oxidation in the livers, thus, the enhanced hepatic inflammation, steatosis and cholesterol deposition synergesticlly resulted in the liver injury.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f6: Proposed mechanisms of HCD induced liver injury in mice.High carbohydrate diet feeding upregualted the expression of miR-34a,which could inhibited the protein expression and activity of NAMPT, SIRT1 and AMPK, then increased the expression of genes related to hepatic inflammatory response, hepatic de novo lipogenesis and cholesterol deposition, decreased the expression of genes involved in fatty acid oxidation in the livers, thus, the enhanced hepatic inflammation, steatosis and cholesterol deposition synergesticlly resulted in the liver injury.
Mentions: In the present study, despite similar energy intake and final body weight by group pair-feeding with the liquid diet, HCLD feeding for 16 weeks significantly increased the liver weight and the ratio of liver weight/body weight, and induced more severity of hepatic steatosis and cholesterol deposition than HFLD feeding. These changes were accompanied with significantly increased DNL related markers (SCD1 and ACC), and decreased mRNA level of genes related to fatty acid oxidation and cholesterol metabolism (Fig. 6). Although the difference in hepatic TG concentrations between HCLD and HFLD feeding mice did not reach statistical significance, this could be due to the fact that the distribution of steatosis in the liver is local, combined with the small portion of liver tissue used for biochemical analysis. We believe that the steatosis grading determined by histopathologic analysis for 20 random fields of the liver tissue section provided more reliable evidence for the hepatic lipid deposition. Meanwhile, HCLD feeding resulted in much higher incidence of hepatic inflammatory response accompanying with the increased expression of pro-inflammatory cytokines. Taken together, the present study provided strong experimental evidence that HCLD feeding, as compared with HFLD feeding, induced more detrimental effects in the liver.

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