Bifidobacterium breve CBT BR3 and Lactiplantibacillus plantarum CBT LP3 Alleviate Hepatic Steatosis by Suppressing Hepatic Lipogenesis and Improving Metabolic Hormone Profiles In Vitro and In Vivo.

Hepatic steatosis is an early key event in metabolic dysfunction-associated steatotic liver disease, for which safe and effective interventions for reducing hepatic lipid accumulation are needed. To this end, we investigated the anti-steatotic effect of combining probiotics Bifidobacterium breve BR3 and Lactiplantibacillus plantarum LP3 (BR3LP3) on an in vitro oleic acid (OA)-treated human hepatocellular carcinoma (HepG2) cell model and an in vivo high-fat diet (HFD)-induced obese mouse model. In the OA-treated HepG2 cell model, BR3LP3 reduced OA-induced lipid accumulation without exhibiting cytotoxicity and modulated lipogenesis-related protein expression, while in the HFD-fed obese mouse model, oral BR3LP3 supplementation reduced body weight, fat mass, liver weight, and epididymal adipose tissue weight and improved several serum lipid, liver injury-related, and metabolic hormone parameters without affecting food intake. Moreover, when comparing BR3LP3-supplemented mice with those fed the HFD only, the former revealed reduced hepatic lipid droplet accumulation via histological analysis, while the expression levels of sterol regulatory element-binding protein-1c (Srebp1c), peroxisome proliferator-activated receptor γ (Pparγ), CCAAT/enhancer-binding protein alpha (Cebpα), acetyl-CoA carboxylase (Acc), and fatty acid synthase (Fas) were lower. Hence, our findings indicate that BR3LP3 supplementation attenuates hepatic lipid accumulation and the expression of hepatic lipogenesis-related markers while improving adiposity and systemic metabolic parameters. This suggests that BR3LP3 supplementation is a promising probiotic dietary strategy for improving hepatic steatosis and related metabolic dysfunction.