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

J Immunol. 2018 Sep 1;201(5):1491-1499. doi: 10.4049/jimmunol.1800321. Epub 2018 Jul 23.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / immunology*
  • Adipocytes / microbiology
  • Adipocytes / pathology
  • Animals
  • Bacteroidaceae Infections / drug therapy*
  • Bacteroidaceae Infections / genetics
  • Bacteroidaceae Infections / immunology
  • Bacteroidaceae Infections / pathology
  • Cytokines / genetics
  • Cytokines / immunology
  • Gene Knockdown Techniques
  • Inflammation / drug therapy
  • Inflammation / genetics
  • Inflammation / immunology
  • Inflammation / pathology
  • Mice
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / immunology*
  • Porphyromonas gingivalis / immunology*
  • Porphyromonas gingivalis / pathogenicity
  • Pyrones / pharmacology*
  • Signal Transduction / drug effects*
  • Signal Transduction / genetics
  • Signal Transduction / immunology

Substances

  • Cytokines
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, mouse
  • Pyrones
  • kavain