Induces Insulin Resistance by Increasing BCAA Levels in Mice.

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 in the development of insulin resistance. However, the mechanisms by which induces insulin resistance are still unclear. The purpose of this study was to investigate whether induces insulin resistance through BCAA biosynthesis. We established a murine model of periodontitis by infecting mice with . Alveolar bone loss, insulin sensitivity, and the plasma level of BCAAs were measured. A BCAA aminotransferase-deficient strain () 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 strain were further measured. We found that periodontal infection with significantly upregulated the plasma level of BCAAs and aggravated the high-fat diet (HFD)-induced insulin resistance. deletion did not alter the growth, biofilm formation, and in vivo colonization of . More important, the 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 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.