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Preventing adverse pregnancy outcomes is crucial for maternal and child health. Periodontal disease is a risk factor for many systemic diseases including adverse pregnancy outcomes, such as preterm birth and low birth weight. In addition, the administration of the periodontopathic bacterium Porphyromonas gingivalis exacerbates obesity, glucose tolerance, and hepatic steatosis and alters endocrine function in the brown adipose tissue (BAT). However, the effects of having periodontal disease during pregnancy remain unclear. Thus, this study investigates the effect of P. gingivalis administration on obesity, liver, and BAT during pregnancy. Sonicated P. gingivalis (Pg) or saline (Co) was injected intravenously and administered orally to pregnant C57BL/6J mice three times per week. Maternal body weight and fetal body weight on embryonic day (ED) 18 were evaluated. Microarray analysis and qPCR in the liver and BAT and hepatic and plasma triglyceride quantification were performed on dams at ED 18. The body weight of Pg dams was heavier than that of Co dams; however, the fetal body weight was decreased in the offspring of Pg dams. Microarray analysis revealed 254 and 53 differentially expressed genes in the liver and BAT, respectively. Gene set enrichment analysis exhibited the downregulation of fatty acid metabolism gene set in the liver and estrogen response early/late gene sets in the BAT, whereas inflammatory response and IL6/JAK/STAT3 signaling gene sets were upregulated both in the liver and BAT. The downregulation of expression levels of Lpin1, Lpin2, and Lxra in the liver, which are associated with triglyceride synthesis, and a decreasing trend in hepatic triglyceride of Pg dams were observed. P. gingivalis administration may alter lipid metabolism in the liver. Overall, the intravenous and oral administration of sonicated P. gingivalis-induced obesity and modified gene expression in the liver and BAT in pregnant mice and caused fetuses to be underweight.

Improvement of obesity is important for increasing longevity. The characteristics, size, and function of adipocytes are altered in patients with obesity. Adipose tissue is not only an energy storage but also an endocrine organ. Alteration of endocrine activities in adipose tissue, among them the functional decline of brown adipose tissue (BAT), is associated with obesity. Periodontal disease is a risk factor for systemic diseases since endotoxemia is caused by periodontal bacteria. However, the effect of periodontal disease on obesity remains unclear. Thus, this study aimed to investigate the effect of endotoxemia due to Porphyromonas gingivalis, a prominent cause of periodontal disease, on the BAT. Herein, endotoxemia was induced in 12-week-old C57BL/6J mice through intravenous injection of sonicated 108 CFU of P. gingivalis (Pg) or saline (control [Co]) once. Eighteen hours later, despite no inflammatory M1 macrophage infiltration, inflammation-related genes were upregulated exclusively in the BAT of Pg mice compared with Co mice. Although no marked histological changes were observed in adipose tissues, expressions of genes related to lipolysis, Lipe and Pnpla2 were downregulated after P. gingivalis injection in BAT. Furthermore, expression of Pparg and Adipoq was downregulated only in the BAT but not in the white adipose tissues, along with downregulation of Ucp1 and Cidea expression, which are BAT-specific markers, in Pg mice. Microarray analysis of the BAT showed 106 differentially expressed genes between Co and Pg mice. Gene set enrichment analysis revealed that the cholesterol homeostasis gene set and PI3/Akt/mTOR signaling gene set in BAT were downregulated, whereas the TGF-β signaling gene set was enriched in Pg mice. Overall, intravenous injection of sonicated P. gingivalis altered the endocrine functions of the BAT in mice. This study indicates that endotoxemia by P. gingivalis potentially affects obesity by disrupting BAT function.

Several reports have shown that the photo-bio-modulation of cells by various lasers has favorable biological effects. However, the effects of low-level Er:YAG laser irradiation on osteoblasts remain unclear. The purpose of this study was to evaluate the effects of low-level Er:YAG laser irradiation on proliferation and osteogenic differentiation of primary osteoblast-like cells isolated from the calvariae of 3–5-day-old Wistar rats. Cells were irradiated by Er:YAG laser at energy fluences of 2.2, 3.3, and 4.3 J/cm2, respectively. After irradiation, cell surface temperatures were measured and cell proliferation was evaluated by flow cytometry and CCK-8. Calcification was evaluated by measuring areas of Alizarin red S staining after 7, 14, and 21 days culture in osteoinductive medium. Gene expression in non-irradiated and laser-irradiated cells was evaluated by qPCR at 3, 6, and 12 h, as well as 1, 3, 7, and 14 days after irradiation. Microarray analysis was performed to comprehensively evaluate the gene expression of non-irradiated and irradiated cells at 3.3 J/cm2 at 6 h after irradiation. No pronounced increase of cell surface temperature was induced by irradiation. Irradiation did not affect osteoblast-like cell proliferation. Osteoblast-like cell calcification was significantly increased 7 days after Er:YAG laser irradiation at 3.3 J/cm2. Bglap expression was significantly increased in cells irradiated at 3.3 J/cm2 6 h post-irradiation. Microarray analysis showed that irradiation at 3.3 J/cm2 caused an upregulation of inflammation-related genes and downregulation of Wisp2. Gene set enrichment analysis also clarified enrichment of inflammation-related and Notch signaling gene sets. In conclusion, low-level Er:YAG laser irradiation at 3.3 J/cm2 enhanced calcification of primary osteoblast-like cells via enhanced Bglap expression and enriched Notch signaling.