Anti-inflammatory and Anti-adipogenic Effects of Pediococcus pentosaceus TAP041 Under AGE-Associated Conditions
摘要
Advanced glycation end products (AGEs) contribute to chronic inflammation and metabolic dysregulation and are closely associated with obesity-related disorders. Probiotics have emerged as promising functional agents capable of modulating immune and metabolic responses. In this study, the anti-inflammatory and anti-adipogenic effects of Pediococcus pentosaceus TAP041 were investigated using lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and 3T3-L1 preadipocytes, with a particular focus on AGE-associated adipogenesis. Treatment with P. pentosaceus TAP041 attenuated LPS-induced responses in RAW264.7 macrophages, as evidenced by reduced nitric oxide production, downregulation of inducible nitric oxide synthase, cyclooxygenase-2, and interleukin-6, and concomitant upregulation of the anti-inflammatory cytokine, interleukin-10. These effects were associated with selective inhibition of p38 mitogen-activated protein kinase phosphorylation, whereas ERK and JNK signaling remained largely unaffected. In 3T3-L1 adipocytes, P. pentosaceus TAP041 suppressed adipogenic differentiation and lipid accumulation, without inducing cytotoxicity. Co-treatment with P. pentosaceus TAP041 markedly attenuated Nε-(carboxymethyl)lysine-induced lipid accumulation. This anti-adipogenic effect was accompanied by coordinated downregulation of key adipogenesis- and lipogenesis-related genes, including sterol regulatory element-binding protein-1c, peroxisome proliferator-activated receptor-δ, adiponectin, acetyl-CoA carboxylase, fatty acid synthase, and lipoprotein lipase. Collectively, these findings demonstrate that P. pentosaceus TAP041 exerts dual regulatory effects on inflammatory activation and adipogenic differentiation by modulating macrophage inflammatory signaling and adipocyte lipid metabolism. This study provides mechanistic evidence supporting the potential of P. pentosaceus TAP041 as a functional probiotic candidate for mitigating inflammation- and AGE-associated metabolic disturbances.