Adipose tissue inflammation mediated by CCL19 overexpression exacerbates experimental periodontitis via elevated circulating saturated fatty acids and osteopontin in Western-diet-fed mice

ABSTRACT: Introduction: Individuals with obesity may be at a higher risk of developing severe periodontitis. We previously reported that C-C motif ligand 19 (CCL19) plays a pivotal role in adipose inflammation in obesity and that adipocyte-specific Ccl19 knock-in (CCL19-KI) mice exhibited greater inflammatory cell infiltration in visceral fat, increased weight gain, and abnormal glucose metabolism than wild-type (WT) mice under a 40% high-fat diet (HFD). In this study, we examined the susceptibility of mice fed diets with different fat contents to the severity of experimental periodontitis. Methods: Six-week-old male WT and CCL19-KI mice were fed either a normal diet (ND), 40% HFD, or 60% HFD for 8 weeks, after which ligature-induced periodontitis (LIP) was established. Two weeks after ligation, alveolar bone resorption, gingival inflammatory and osteoclastogenic gene expression, and serum free fatty acid (FFA) levels were compared among the groups. Additionally, RNA-sequencing (RNA-seq) was performed on epididymal white adipose tissue (eWAT) of each ligatured mouse to explore potential factors mediating periodontitis aggravation. Furthermore, in vitro studies using macrophages were conducted to investigate a possible mechanism in the progression of periodontitis. Results: Alveolar bone resorption, gingival inflammatory and osteoclastogenic gene expression, and serum FFA levels were significantly higher in ligated CCL19-KI mice than those in ligated WT mice under a 40% HFD. RNA-seq revealed that the OPN gene (Spp1) expression in eWAT was significantly upregulated in CCL19-KI mice fed an ND or 40% HFD compared with that in WT mice, which was consistent with serum OPN levels. Peritoneal macrophages from 40% HFD-fed CCL19-KI mice secreted significantly higher amounts of TNF-a than those from WT mice fed the same diet under Escherichia coli lipopolysaccharide (LPS) stimulation. Both palmitic acid priming and OPN significantly promoted osteoclastogenesis in RANKL-treated BMMs, and their combination further enhanced this effect. Conclusions: CCL19-modified adipose tissue inflammation may contribute to the severity of periodontitis via the upregulation of circulating saturated fatty acids and Spp1, resulting in enhanced TNF-a production in macrophages and increased osteoclastogenesis in BMMs under mild to moderate obesity.

ORGANISM(S): Mus musculus

PROVIDER: GSE328134 | GEO | 2026/04/22

REPOSITORIES: GEO