Effects of Porphyromonas gingivalis Bacteria on Inflammation, Oxidative Stress and Lipid Metabolism in Models of Obese db/db Mice and 3T3-L1 Adipose Cells

During periodontitis, <i>Porphyromonas gingivalis</i> and its lipopolysaccharides (LPS) may translocate into the bloodstream and alter adipocyte function, aggravating obesity-related disorders. This study aimed to evaluate the inflammatory and metabolic effects of <i>P. gingivalis</i> in obese <i>db</i>/<i>db</i> mice, and to decipher the molecular mechanisms targeted by <i>P. gingivalis</i> or its LPS in 3T3-L1 adipocytes. Then, we determined the ability of three major dietary polyphenols, namely caffeic acid, quercetin and epicatechin, to protect adipocytes under LPS conditions. Results show that obese mice exposed to <i>P. gingivalis</i> exhibited an altered lipid profile with higher triglyceride accumulation, an enhanced pro-inflammatory response and a reduced antioxidant SOD activity in the adipose tissue. In adipose cells, <i>P. gingivalis</i> and LPS induced the TLR2-4/MyD88/NFκB signaling pathway, and promoted IL-6 and MCP-1 secretion. Bacterial stimuli also increased ROS levels and the expression of <i>NOX2</i>, <i>NOX4</i> and <i>iNOS</i> genes, while they deregulated mRNA levels of Cu/ZnSOD, MnSOD, catalase, GPx and Nrf2. Interestingly, caffeic acid, quercetin and epicatechin protected adipose cells via antioxidant and anti-inflammatory effects. Overall, these findings show the deleterious impact of <i>P. gingivalis</i> on inflammation, oxidative stress and lipid metabolism in obese mice and adipose cells, and highlight the therapeutic potential of polyphenols in mitigating periodontal bacteria-mediated complications during obesity.