Porphyromonas gingivalis Induces Insulin Resistance by Increasing BCAA Levels in Mice
Abstract
Insulin resistance is one of the critical pathogeneses of type 2 diabetes mellitus (T2DM). Elevated levels of plasma branched-chain amino acids (BCAAs) are associated with insulin resistance. Recent studies have demonstrated the role of Porphyromonas gingivalis in the development of insulin resistance. However, the mechanisms by which P. gingivalis induces insulin resistance are still unclear. The purpose of this study was to investigate whether P. gingivalis induces insulin resistance through BCAA biosynthesis. We established a murine model of periodontitis by infecting mice with P. gingivalis. Alveolar bone loss, insulin sensitivity, and the plasma level of BCAAs were measured. A P. gingivalis BCAA aminotransferase-deficient strain (∆bcat) was constructed, and its kinetic growth, biofilm formation, and in vivo colonization were compared with its wild-type strain. Alveolar bone loss, insulin sensitivity, and the plasma level of BCAAs of the mice infected with either wild-type strain or ∆bcat strain were further measured. We found that periodontal infection with P. gingivalis significantly upregulated the plasma level of BCAAs and aggravated the high-fat diet (HFD)–induced insulin resistance. Bcat deletion did not alter the growth, biofilm formation, and in vivo colonization of P. gingivalis. More important, the ∆bcat strain was unable to upregulate the plasma level of BCAAs and induce insulin resistance in HFD-fed mice. These findings suggest that the BCAA biosynthesis of P. gingivalis plays a critical role in the development of insulin resistance in the HFD-fed mice. The BCAA biosynthesis pathways may provide a potential target for the disruption of linkage between periodontitis and T2DM.
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Article first published online: March 16, 2020
Issue published: July 2020
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PubMed: 32176550
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