Resveratrol improves non-alcoholic fatty liver disease by activating AMP-activated protein kinase

Abstract

Aim: To investigate whether resveratrol (RSV) can improve non‐alcoholic fatty liver disease (NAFLD) and to find the possible mechanism. Methods: Rats fed a high‐fat diet were treated with RSV. The liver histology was observed. Hyperinsulinemic euglycemic clamp was performed to assess insulin sensitivity. Fat accumulation was induced in HepG2 cells, and the cells were treated with RSV. AMP‐activated protein kinase (AMPK) phosphorylation levels were determined both in the animal study and cell study. Results: Rats fed a high‐fat diet developed abdominal obesity, NAFLD, and insulin resistance (IR), which were markedly improved by 10 weeks of RSV administration. RSV treatment prevented triacylglycerol (TG) accumulation in HepG2 cells that were incubated with high concentration of glucose and insulin. Both in vivo and in vitro studies showed that RSV treatment could promote the phosphorylation of AMPK, which in this study, suppressed 2 lipogenesis gene expressions, contributing to the improvement of NAFLD and IR. Conclusion: The results indicated that by reducing TG accumulation and improving IR, RSV could protect the liver from NAFLD. The activation of AMPK was involved in the mechanism. RSV has the therapeutic potential for preventing or treating NAFLD and IR‐related metabolic disorders.

Potensi Suplementasi Resveratrol dalam Mengatasi Efek Negatif Hormon Tiroid pada Terapi Obesitas: Uji Preklinik

“…Perbaikan resistensi insulin oleh RSV diduga melalui peningkatan aktivitas SIRT-1 dan adenosine monophosphate-activated protein kinase (AMPK) sehingga menghambat glukoneogenesis hepatik, meningkatkan ambilan glukosa pada otot skeletal, dan merangsang pengeluaran insulin melalui sel-β pankreas. 14,15 Walau secara fenotip (bobot badan, massa otot, indeks adiposit, serta AUC glukosa) suplementasi RSV pada terapi obesitas dengan HT3 memperlihatkan hasil yang signifikan, namun efek ini tidak terlihat pada pengukuran parameter stres oksidatif (kadar MDA plasma) dan kerusakan DNA yang ditimbulkan oleh HT3 (p>0,05). Beberapa dugaan yang dapat menjelaskan hasil tersebut antara lain berkaitan dengan dosis dan lama pemberian RSV serta besar sampel.…”

Oxidative stress: New insights on the association of non-alcoholic fatty liver disease and atherosclerosis

“…The mechanism of action underlying this effect may be mediated by a decrease of de novo lipogenesis [105][106][107][108] . Many in vivo studies demonstrated positive effects on liver steatosis in animal models, showing efficacy both for fatty liver prevention and treatment [108,109] . The doses used in these studies have been generally very high, ranging from 0.5 to 450 mg/kg per day.…”

Yhhu981, a novel compound, stimulates fatty acid oxidation via the activation of AMPK and ameliorates lipid metabolism disorder in ob/ob mice

“…Consistent with an effect on AMPK activation, the phosphorylation of the AMPK substrate ACC was also significantly increased (Figure 2A-2D). AMPK activation is associated with improved lipid metabolism in rodents [26][27][28] . To determine whether AMPK activation mediates elevated fatty acid oxidation by yhhu981, we pre-incubated C2C12 myotubes with the AMPK inhibitor compound C for 30 min before co-incubation with yhhu981.…”