Kavain Reduces Porphyromonas gingivalis-Induced Adipocyte Inflammation: Role of PGC-1α Signaling.

ABSTRACT

A link between obesity and periodontitis has been suggested because of compromised immune response and chronic inflammation in obese patients. In this study, we evaluated the anti-inflammatory properties of Kavain, an extract from Piper methysticum, on Porphyromonas gingivalis-induced inflammation in adipocytes with special focus on peroxisome proliferation-activated receptor γ coactivator α (PGC-1α) and related pathways. The 3T3-L1 mouse preadipocytes and primary adipocytes harvested from mouse adipose tissue were infected with P. gingivalis, and inflammation (TNF-α; adiponectin/adipokines), oxidative stress, and adipogenic marker (FAS, CEBPα, and PPAR-γ) expression were measured. Furthermore, effect of PGC-1α knockdown on Kavain action was evaluated. Results showed that P. gingivalis worsens adipocyte dysfunction through increase of TNF-α, IL-6, and iNOS and decrease of PGC-1α and adiponectin. Interestingly, although Kavain obliterated P. gingivalis-induced proinflammatory effects in wild-type cells, Kavain did not affect PGC-1α-deficient cells, strongly advocating for Kavain effects being mediated by PGC-1α. In vivo adipocytes challenged with i.p. injection of P. gingivalis alone or P. gingivalis and Kavain displayed the same phenotype as in vitro adipocytes. Altogether, our findings established anti-inflammatory and antioxidant effects of Kavain on adipocytes and emphasized protective action against P. gingivalis-induced adipogenesis. The use of compounds such as Kavain offer a portal to potential therapeutic approaches to counter chronic inflammation in obesity-related diseases.