To explore the molecular mechanism of berberine in improving insulin resistance and liver lipid metabolism in obesity mice.

Sixty clean-grade C57BL/6 mice were randomly divided into control group (normal diet), model group (high fat diet), experimental-L group (model+50.00 mg·kg^-1 berberine), experimental-H group (model+100.00 mg·kg^-1 berberine), inhibitor NC group (model +100.00 mg·kg^-1 berberine + tail vein injection mmu-inhibitor NC), miR-125a inhibitor group (model +100.00 mg·kg^-1 berberine + tail vein injection of mmu-miR-125a inhibitor). Berberine was administered by gavage once a day, and subcutaneous injection was performed every 4 days. After a continuous treatment period of 28 days, the insulin resistance levels were detected, serum lipid levels were analyzed, the expression levels of related genes were detected by real-time quantitative polymerase chain reaction (RT-qPCR), and the expression of related proteins in liver tissue was detected by Western blot (WB).

The levels homeostatis model assessment of insulin resistance (HOMA-IR) in control group, model group, experimental-H group, inhibitor NC group and miR-125a inhibitor group were 2.56±0.11, 7.23±0.67, 5.04±0.20, 4.99±0.34 and 6.46±0.40, respectively; triglyceride (TG) levels were (0.46±0.04), (0.93±0.08), (0.65±0.05), (0.63±0.06) and (0.74±0.06) mmol·L^-1, respectively; the relative expression levels of miR-125a were 1.00±0.12, 0.56±0.07, 0.77±0.10, 0.78±0.11 and 0.21±0.03, respectively; fatty acid synthase (FAS) mRNA were 1.00±0.10, 1.90±0.14, 1.40±0.22, 1.41±0.16 and 1.67±0.14, respectively; the relative protein expression levels of phosphorylated phosphatidylase 3-kinase (p-PI3K) were 0.78±0.09, 0.42±0.05, 0.69±0.06, 0.70±0.03 and 0.51±0.06, respectively; phosphorylated protein kinase B (p-AKT) protein levels were 0.84±0.12, 0.30±0.05, 0.64±0.08, 0.65±0.08 and 0.49±0.07, respectively. Compared between the model group and the control group; between the experimental-H group and the model group; and between the miR-125a inhibitor group and the inhibitor NC group, all differences of the above inclicatovs went statistically significant (P<0.01, P<001).

Berberine may improve insulin resistance and fat metabolism in obesity mice by activating PI3K/AKT signal through miR-125a.