In conclusion, L‐14 extract from Lactobacillus significantly inhibits the differentiation of mouse 3T3‐L1 cells and hBM‐MSCs to mature adipocytes via AMPK and PPARγ signalling pathways and alleviates systemic inflammation and obesity in vivo in an HFD mouse model. Here, PPARG is linked to obesity due to melanocortin 4 receptor deficiency.