Possible Involvement of Palmitate in Pathogenesis of Periodontitis.
Type 2 diabetes (T2D) is characterized by decreased insulin sensitivity and higher concentrations of free fatty acids (FFAs) in plasma. Among FFAs, saturated fatty acids (SFAs), such as palmitate, have been suggested to promote inflammatory responses. Although many epidemiological studies have shown a link between periodontitis and T2D, little is known about the clinical significance of SFAs in periodontitis. In this study, we showed that gingival fibroblasts have cell-surface expression of CD36, which is also known as FAT/fatty acid translocase. Moreover, CD36 expression was increased in gingival fibroblasts of high-fat diet-induced T2D model mice, compared with gingival fibroblasts of mice fed a normal diet. DNA microarray analysis revealed that palmitate increased mRNA expression of pro-inflammatory cytokines and chemokines in human gingival fibroblasts (HGF). Consistent with these results, we confirmed that palmitate-induced interleukin (IL)-6, IL-8, and CXCL1 secretion in HGF, using a cytokine array and ELISA. SFAs, but not an unsaturated fatty acid, oleate, induced IL-8 production. Docosahexaenoic acid (DHA), which is one of the omega-3 polyunsaturated fatty acids, significantly suppressed palmitate-induced IL-6 and IL-8 production. Treatment of HGF with a CD36 inhibitor also inhibited palmitate-induced pro-inflammatory responses. Finally, we demonstrated that Porphyromonas gingivalis (P.g.) lipopolysaccharide and heat-killed P.g. augmented palmitate-induced chemokine secretion in HGF. These results suggest a potential link between SFAs in plasma and the pathogenesis of periodontitis.
Clinical Research Center for Diabetes, Tokushima University Hospital, Tokushima, Japan.
Yosuke
Y
Shikama
Department of Oral Molecular Pathology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
Yasusei
Y
Kudo
Department of Oral Molecular Pathology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
Naozumi
N
Ishimaru
Clinical Research Center for Diabetes, Tokushima University Hospital, Tokushima, Japan.
Makoto
M
Funaki
D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism; D045744:Cell Line, Tumor; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000235:genetics; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D005881:Gingiva / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008810:Mice, Inbred C57BL; D019308:Palmitic Acid / Q000097:blood / Q000494:pharmacology*; D010518:Periodontitis / Q000097:blood / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D016966:Porphyromonas gingivalis; D013997:Time Factors
D018955:CD36 Antigens; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D019308:Palmitic Acid