Lactiplantibacillus plantarum Ln4 Alleviates High-Fat Diet-Induced Obesity by Modulating Lipid Metabolism and Adipogenesis in C57BL/6 Mice

Background/Objectives: This research examined the anti-obesity potential of Lactiplantibacillus plantarum Ln4 in C57BL/6 mice fed a high-fat diet (HFD) for eight weeks. Methods: Forty male mice were randomly assigned (n = 8 per group) a normal diet (ND), HFD, HFD with orlistat (positive control), or HFD supplemented with Ln4 at 5 × 108 or 5 × 109 CFU/day (Ln4-8, Ln4-9). Ln4 was orally administered once daily throughout the study period. Results: Ln4 supplementation significantly attenuated body weight gain, visceral fat accumulation, and dyslipidemia, while improving lipid metabolism and hormonal balance. The Ln4-9 group exhibited effects comparable to those of orlistat, indicating potent anti-obesity activity. Ln4 also reduced serum triglyceride and total cholesterol concentrations and improved lipid and hormone profiles. At the molecular level, Ln4 downregulated adipogenic and lipogenic regulators (PPARγ, SREBP1c, and C/EBPα) while upregulating genes involved in lipolysis and fatty acid oxidation (PPARα, CPT1, and ACO) in the liver and adipose tissue. These changes were accompanied by lower insulin and leptin levels and restored adiponectin concentrations. Conclusions: Collectively, the results demonstrate that L. plantarum Ln4 mitigates HFD-induced obesity by improving lipid metabolism, suppressing adipogenesis, and balancing metabolic hormones, suggesting its potential as a functional probiotic for obesity management.