Salidroside inhibits insulin resistance and hepatic steatosis by downregulating miR-21 and subsequent activation of AMPK and upregulation of PPARα in the liver and muscles of high fat diet-fed rats

Abstract

This study evaluated if salidroside (SAL) alleviates high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) by downregulating miR-21. Rats (n = 8/group) were treated for 12 weeks as normal diet (control/ND), ND + agmoir negative control (NC) (150 µg/kg), ND + SAL (300 mg/kg), HFD, HFD + SAL, HFD + compound C (an AMPK inhibitor) (200 ng/kg), HFD + SAL + NXT629 (a PPAR-α antagonist) (30 mg/kg), and HFD + SAL + miR-21 agomir (150 µg/kg). SAL improved glucose and insulin tolerance and preserved livers in HFD-fed rats. In ND and HFD-fed rats, SAL reduced levels of serum and hepatic lipids and the hepatic expression of SREBP1, SREBP2, fatty acid (FA) synthase, and HMGCOAR. It also activated hepatic Nrf2 and increased hepatic/muscular activity of AMPK and levels of PPARα. All effects afforded by SAL were prevented by CC, NXT629, and miR-21 agmoir. In conclusion, activation of AMPK and upregulation of PPARα mediate the anti-steatotic effect of SAL.

Keywords:

• HFD
• NAFLD
• insulin resistance
• miR-21
• salidroside
• SREBPs
• steatosis
• rats

Acknowledgments

The authors would like to thank Princess Nourah bint Abdulrahman University Researchers Supporting Project number (PNURSP2022R222), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia. The authors would also like to thank the Deanship of Scientific Research at King Khalid University, Abha, KSA for funding this work under Grant number (R.G.P.1/62/42).

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability statement

The data used to support the findings of this study are included within the article.

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work was supported by the Taif University Researchers Supporting Program (Project number: TURSP-2020/99), Taif University, Saudi Arabia.