Resveratrol attenuates against high-fat-diet-promoted non-alcoholic fatty liver disease in rats mainly by targeting the miR-34a/SIRT1 axis.
Mona Nasser BinMowynaNora Abdullah AlFarisEkram A Al-SaneaJozaa Z ALTamimiTahany Saleh AldayelPublished in: Archives of physiology and biochemistry (2022)
This study evaluated if miR-34a/SIRT1 signalling mediates the anti-hepatosteatotic effect of resveratrol (RSV) in high-fat-diet (HFD)-fed rats. Rats were divided into seven groups ( n = 6/each) as control, control + miR-34a agomir negative control, HFD, HFD + miR-34a, HFD + RSV, HFD + RSV + Ex-527 (a SIRT1 inhibitor), and HFD + RSV + miR-34a agomir. After 8 weeks, RSV suppressed dyslipidemia, lowered fasting glucose and insulin levels, improved insulin sensitivity, and prevented hepatic lipid accumulation. These effects were associated with hepatic downregulation of SREBP1 and SREBP2, upregulation of PPARα, and acetylation of Nrf2 (activation) and NF-κβ p65 (inhibition). Also, RSV reduced the transcription of miR-34a and increased the nuclear localisation of SIRT1 in the livers, muscles, and adipose tissues of HFD-fed rats. All these effects were prevented by EX-527 and miR-34a agmir. In conclusion, RSV prevents HFD-induced insulin resistance and hepatic steatosis by suppressing miR-34a-induced activation of SIRT1.
Keyphrases
- high fat diet
- insulin resistance
- cell proliferation
- long non coding rna
- adipose tissue
- long noncoding rna
- respiratory syncytial virus
- oxidative stress
- metabolic syndrome
- respiratory tract
- skeletal muscle
- type diabetes
- polycystic ovary syndrome
- poor prognosis
- high fat diet induced
- pi k akt
- signaling pathway
- ischemia reperfusion injury
- gene expression
- transcription factor
- blood pressure
- mouse model
- immune response
- high glucose
- preterm birth
- diabetic rats
- nuclear factor
- gestational age
- histone deacetylase