Positive metabolic effects of selected probiotic bacteria on diet-induced obesity in mice are associated with improvement of dysbiotic gut microbiota

Given the rising evidence that gut malfunction including changes in the gut microbiota composition, plays a major role in the development of obesity and associated metabolic diseases, the exploring of novel probiotic bacteria with potential health benefits has attracted great attention. RecentlyLactobacillusspp., exert potent anti-obesity effects by regulating key transcriptional and translational factors in adipose tissues. However, the molecular mechanism behind the anti-obesity effect of probiotics is not yet fully understood. Therefore, we investigated the effect ofLactobacillus plantarumA29 on the expression of adipogenic and lipogenic genes in 3T3-L1 adipocytes and high-fat diet (HFD)-fed mice. We observed that the treatment of 3T3-L1 adipocytes with the cell-free metabolites ofL plantaruminhibited their differentiation and fat depositions via downregulating the key adipogenic transcriptional factors (PPAR-gamma, C/EBP-alpha, and C/EBP-beta) and their downstream targets (FAS, aP2, ACC, and SREBP-1). Interestingly, supplementation withL plantarumreduced the fat mass and serum lipid profile concurrently with downregulation of lipogenic gene expression in the adipocytes, resulting in reductions in the bodyweight of HFD-fed obese mice.L plantarumtreatment attenuated the development of obesity in HFD-fed mice via the activation of p38MAPK, p44/42, and AMPK-alpha by increasing their phosphorylation. Further analysis revealed that A29 modulated gut-associated microbiota composition. Thus, A 29 potential probiotic strain may alleviate the obesity development and its associated metabolic disorders via inhibiting PPAR gamma through activating the p38MAPK and p44/42 signaling pathways.