Quercetin combined with cinnamaldehyde ameliorates insulin resistance via modulation of the G protein-coupled receptor 120/p38 mitogen-activated protein kinase/Kruppel-like factor 15 signaling pathway
Caiwen Ou, Fujia Lin, Peifeng Ke, Jinqi YuObjective
We aimed to investigate the enhanced beneficial effect of quercetin and cinnamaldehyde on improving insulin resistance in vitro and in vivo and to elucidate the underlying mechanism involving the G protein-coupled receptor 120 (GPR120)/p38 mitogen-activated protein kinase (MAPK)/Kruppel-like factor 15 (KLF15) signaling pathway.
Methods
Palmitic acid–induced 3T3-L1 adipocyte insulin resistance model and a high-fat diet–combined palmitic acid–induced rat insulin resistance model were established. The cells and rats were treated with quercetin, cinnamaldehyde, or their combination. Glucose consumption in the adipocytes was measured using the glucose oxidase method. Glucose tolerance and insulin tolerance tests were performed in the rats. Serum levels of lipid profile parameters (triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol) and blood glucose were measured using an automatic biochemical analyzer. The mRNA and protein expression levels of GPR120, p38 MAPK, phospho-p38 (p-p38) MAPK, KLF15, and GLUT-4 were determined using quantitative reverse transcription polymerase chain reaction and Western blot analysis. To validate the underlying mechanism, GPR120 and KLF15 overexpression and KLF15 silencing were performed in adipocytes.
Results
In palmitic acid–induced 3T3-L1 adipocytes, quercetin and cinnamaldehyde alone enhanced glucose consumption, downregulated GPR120 and p-p38 MAPK expressions, and upregulated KLF15 expression compared with those in the insulin resistance model group. The combination treatment demonstrated a more significant effect (all
Conclusion
The combination of quercetin and cinnamaldehyde exerted an enhanced beneficial effect in improving insulin resistance, which was associated with modulation of the GPR120/p38 MAPK/KLF15 signaling pathway, providing a potential therapeutic strategy for insulin resistance–related diseases.