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Effect of miR-34a in regulating steatosis by targeting PPARα expression in nonalcoholic fatty liver disease.

Ding J, Li M, Wan X, Jin X, Chen S, Yu C, Li Y - Sci Rep (2015)

Bottom Line: The upregulation of miR-34a resulted in the downregulation of hepatic PPARα and SIRT1 that are the direct targets of miR-34a.Activation of the central metabolic sensor AMPK was also increased.The miR-34a inhibitor suppressed lipid accumulation and improved the degree of steatosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious Diseases, Hangzhou First People's Hospital, No. 261 Huansha Road, Hangzhou 310006, Zhejiang Province, China.

ABSTRACT
MicroRNA-34a (miR-34a) is thought to be involved in nonalcoholic fatty liver disease (NAFLD). However, the association between altered expression of miR-34a and the pathophysiological features of NAFLD remains unclear. Here, we investigated the mechanisms by which miR-34a influences NAFLD through the PPARα-related pathway. Real-time quantitative PCR, western blotting and other assays kit were used to investigate the expression and function of miR-34a in an NAFLD model. Cultured cells transfected with miR-34a inhibitor and C57BL/6 mice injected with the miR-34a inhibitor through vein tail were conducted for the effects of miR-34a on its target. MiR-34a levels were significantly upregulated in steatosis-induced hepatocytes and in liver tissues of high-fat diet-fed mice. The upregulation of miR-34a resulted in the downregulation of hepatic PPARα and SIRT1 that are the direct targets of miR-34a. Silencing miR-34a led to an initially increased expression of PPARα, SIRT1 and PPARα's downstream genes. Activation of the central metabolic sensor AMPK was also increased. The miR-34a inhibitor suppressed lipid accumulation and improved the degree of steatosis. Taken together, our data indicated that decreased expression of miR-34a potentially contributes to altered lipid metabolism in NAFLD. Downregulation of miR-34a may be a therapeutic strategy against NAFLD by regulating its target PPARα and SIRT1.

No MeSH data available.


Related in: MedlinePlus

Summarize of miR-34a-PPARα-AMPK regulation in steatosis.First, miR-34a inhibitor treatment increased the expression of PPARα and SIRT1, then PPARα and SIRT1 activated the AMPK pathway. PPARα and pAMPKα1 increased fat oxidation and improve the steatosis finally.
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f6: Summarize of miR-34a-PPARα-AMPK regulation in steatosis.First, miR-34a inhibitor treatment increased the expression of PPARα and SIRT1, then PPARα and SIRT1 activated the AMPK pathway. PPARα and pAMPKα1 increased fat oxidation and improve the steatosis finally.

Mentions: Activated (phosphorylated) AMPK levels were also observed in whole liver extracts of mice treated with the miR-34a inhibitor (2 × 107 TU) compared with the NC. The total AMPKα1 protein level was unchanged in the miR-34a inhibitor-treated mice, but the levels of phosphorylated AMPKα1 were increased nearly 2-fold compared with the NC (Fig. 5B). Figure 6 showed the summarizing of miR-34a-PPARα-AMPK regulation in steatosis.


Effect of miR-34a in regulating steatosis by targeting PPARα expression in nonalcoholic fatty liver disease.

Ding J, Li M, Wan X, Jin X, Chen S, Yu C, Li Y - Sci Rep (2015)

Summarize of miR-34a-PPARα-AMPK regulation in steatosis.First, miR-34a inhibitor treatment increased the expression of PPARα and SIRT1, then PPARα and SIRT1 activated the AMPK pathway. PPARα and pAMPKα1 increased fat oxidation and improve the steatosis finally.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4557122&req=5

f6: Summarize of miR-34a-PPARα-AMPK regulation in steatosis.First, miR-34a inhibitor treatment increased the expression of PPARα and SIRT1, then PPARα and SIRT1 activated the AMPK pathway. PPARα and pAMPKα1 increased fat oxidation and improve the steatosis finally.
Mentions: Activated (phosphorylated) AMPK levels were also observed in whole liver extracts of mice treated with the miR-34a inhibitor (2 × 107 TU) compared with the NC. The total AMPKα1 protein level was unchanged in the miR-34a inhibitor-treated mice, but the levels of phosphorylated AMPKα1 were increased nearly 2-fold compared with the NC (Fig. 5B). Figure 6 showed the summarizing of miR-34a-PPARα-AMPK regulation in steatosis.

Bottom Line: The upregulation of miR-34a resulted in the downregulation of hepatic PPARα and SIRT1 that are the direct targets of miR-34a.Activation of the central metabolic sensor AMPK was also increased.The miR-34a inhibitor suppressed lipid accumulation and improved the degree of steatosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious Diseases, Hangzhou First People's Hospital, No. 261 Huansha Road, Hangzhou 310006, Zhejiang Province, China.

ABSTRACT
MicroRNA-34a (miR-34a) is thought to be involved in nonalcoholic fatty liver disease (NAFLD). However, the association between altered expression of miR-34a and the pathophysiological features of NAFLD remains unclear. Here, we investigated the mechanisms by which miR-34a influences NAFLD through the PPARα-related pathway. Real-time quantitative PCR, western blotting and other assays kit were used to investigate the expression and function of miR-34a in an NAFLD model. Cultured cells transfected with miR-34a inhibitor and C57BL/6 mice injected with the miR-34a inhibitor through vein tail were conducted for the effects of miR-34a on its target. MiR-34a levels were significantly upregulated in steatosis-induced hepatocytes and in liver tissues of high-fat diet-fed mice. The upregulation of miR-34a resulted in the downregulation of hepatic PPARα and SIRT1 that are the direct targets of miR-34a. Silencing miR-34a led to an initially increased expression of PPARα, SIRT1 and PPARα's downstream genes. Activation of the central metabolic sensor AMPK was also increased. The miR-34a inhibitor suppressed lipid accumulation and improved the degree of steatosis. Taken together, our data indicated that decreased expression of miR-34a potentially contributes to altered lipid metabolism in NAFLD. Downregulation of miR-34a may be a therapeutic strategy against NAFLD by regulating its target PPARα and SIRT1.

No MeSH data available.


Related in: MedlinePlus