Non‐alcoholic steatohepatitis (NASH) is a chronic liver disease that can develop into hepatocirrhosis and hepatic carcinoma. In recent years, epidemiological and animal studies have reported that Porphyromonas gingivalis (P. gingivalis), a known periodontopathic bacteria, is closely related to NASH. However, previous studies could not demonstrate a direct relationship between periodontitis, P. gingivalis infection, and NASH. The purpose of the present study was to examine the impact of P. gingivalis‐associated periodontitis on the onset and progression of NASH. Forty‐two male Wistar rats were used in this study. Rats were fed a high‐fat diet (HFD) for 12 weeks in order to induce fatty liver. At 4 weeks from the start of feeding, the animals were performed ligature placement around the maxillary first molar tooth in order to induce experimental periodontitis, and then a P. gingivalis slurry was applied around the ligature twice in a week for 8 weeks (HFD/Pg(+) group). Controls were given the slurry without P. gingivalis after ligature placement using the same protocol (HFD/Pg(−) group). Significant increases in alveolar bone resorption and inflammation in periodontal tissue around the molar tooth in the HFD/Pg(+) group were observed when compared with the HFD/Pg(−) group. Moreover, histological images showing NASH characterized by perivenular lipid deposition including big fatty drops, ballooning degeneration, and focal necrosis with inflammatory cells were confirmed in the liver of rats in the HFD/Pg(+) group. Significant increases in alanine aminotransaminase, aspartate aminotransferase, and C‐reactive protein levels were observed in the HFD/Pg(+) group. Furthermore, endotoxin levels in serum in the HFD/Pg(+) group were significantly higher than those in the HFD/Pg(−) group. The present study demonstrated that experimental periodontitis induced by P. gingivalis led to the progression of NASH in rats with fatty liver. Increased levels of endotoxin derived from P. gingivalis infection appear to play a considerable role in the progression of NASH.
The present study suggests that the transfer of P. gingivalis-LPS from the oral cavity to the liver plays an important role in disease exacerbation of NASH.
Recent studies have shown that periodontitis accelerates the progression of obesity-associated metabolic diseases. Thus, we examined the influence of periodontitis on serum biochemical parameters of metabolic disease in a diet-induced obesity (DIO) rat. First, we established the DIO model using ten male rats fed with either basal diet (lean group) or high-fat diet (DIO group) for 12 weeks. Second, to examine the interaction between periodontitis and obesity, we divided 24 DIO rats into the following four groups. (1) Porphyromonas gingivalis (Pg) group was applied with Pg around the maxillary first molar (M1). (2) Ligature group was applied with ligature placement around M1. (3) Ligature/Pg group was treated with both ligature placement and Pg. (4) Control was non-treatment group. Serum biochemical parameters and maxillary histopathology were evaluated at 12 weeks. The DIO model demonstrated significant increases in body weight, serum insulin, alanine aminotransaminase (ALT) levels, and insulin resistance (HOMA-IR) compared to the lean group. In the DIO ligature and ligature/Pg groups, alveolar bone resorption and inflammatory cell infiltration were significantly increased compared to the control. Serum levels of fasting glucose, lactate dehydrogenase, and uric acid were also significantly higher, while the liver damage markers ALT and aspartate aminotransferase were only higher in ligature/Pg group. However, we observed no significant differences between the Pg group and Control. The present study suggested a possibility that periodontitis induced by ligature placement changed serum metabolic parameter regarding organs such as the liver in DIO rat.
Highlights d Single pool of heterogenous stem cells supports homeostasis in mouse spermatogenesis d Stem cells move reversibly between renewal-biased and differentiation-primed states d Stem cell dynamics depends on distinct rates of state transition and cell division d Such multistate dynamics reduces mitotic load, while keeping stem cell density high
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