Here, we demonstrate that administration of Lactobacillus amylovorus KU4 (LKU4), a probiotic bacterium, to mice fed a HFD increased mitochondrial levels and expression of BAT-selective genes in iWAT, with a concomitant increase in body temperature; additionally, we also show that lactate mediates these effects of LKU4 on the browning of white adipocytes by remodeling the PPARγ transcription complex through switching RIP140 to PGC-1α, consequently leading to protection against HFD-induced obesity. This evidence concerns the gene PPARGC1A and obesity due to melanocortin 4 receptor deficiency.