Our study found that berberine treatment can increase TRIB1 expression and improve leptin resistance, thereby adjusting the ratio of OPA1 fusion-promoting form (long, about 100 KDa) and non-fusion-promoting form (short, about 85 KDa), restoring the unbalanced mitochondrial dynamics in obesity, thereby improving the overall quality and function of mitochondria. Here, LEP is linked to obesity due to melanocortin 4 receptor deficiency.