Upregulation of free fatty acid receptors in periodontal tissues of patients with metabolic syndrome and periodontitis

Abstract

Background and objective Metabolic syndrome (MetS) exacerbates periodontitis. Since saturated fatty acid (SFA) is increased in MetS and enhances lipopolysaccharide (LPS)‐induced proinflammatory cytokine expression in macrophages, it has been considered to play a role in MetS‐exacerbated periodontitis. However, it remains unknown how fatty acid receptors, which mediate the interaction of cells with SFA and uptake of SFA, are expressed and regulated in the periodontal tissue. In this study, we tested our hypothesis that the periodontal expression of fatty acid receptors GPR40 and CD36 is increased in patients with both MetS and periodontitis. We also determined the effect of SFA and LPS on GPR40 and CD36 expression in vitro. Material and methods Periodontal tissue specimens were collected from 11 participants without MetS and periodontitis, 12 participants with MetS, 11 participants with periodontitis, and 14 participants with both MetS and periodontitis after surgeries. The tissues were processed, and GPR40 and CD36 were detected by immunohistochemistry. Furthermore, cultured macrophages and gingival fibroblasts were treated with LPS, palmitate, a major SFA, or LPS plus palmitate and the expression of GPR40 and CD36 was then quantified. Results Analysis of clinical data showed that age, smoker, gender, and race/ethnicity were not significantly different among 4 groups. Immunohistochemistry showed that GPR40 and CD36 were expressed by epithelial cells, fibroblasts, and immune cells. Quantitative data showed that GPR40 expression is increased in patients with periodontitis, MetS, or both periodontitis and MetS while CD36 expression is increased only in patients with both periodontitis and MetS. The in vitro studies showed that the expression of GPR40 and CD36 in macrophages and fibroblasts was upregulated by the combination of LPS and palmitate. Conclusion Periodontal expression of GPR40 and CD36 was upregulated in patients with both MetS and periodontitis, and GPR40 and CD36 in macrophages and fibroblasts were upregulated in vitro by the combination of LPS and palmitate, suggesting that GPR40 and CD36 may be involved in MetS‐exacerbated periodontitis.

Protective Effects of Omega-3 Fatty Acids in Cancer-Related Complications

“…More recently, it was observed that the FFA1 receptor is expressed in the melanocortin system, specifically in the neuropeptide Y/Agouti-related peptide (NPY/AgRP) and proopiomelanocortin/cocaine- and amphetamine-regulated transcript (POMC/CART) neurons [55]. Interestingly, the FFA1 expression is upregulated in other tissues under pathological situations, such as periodontitis, which is associated with metabolic syndrome [56]. Regarding the antidiabetic effect, FFA1 has been widely investigated as a molecular target for diabetes, mainly due to the glucose-stimulated insulin secretion via protein kinase C/inositol triphosphate (PKC/IP 3 ) activation and, consequently, intracellular calcium increase, inducing insulin release [57,58].…”

The Impact of Diet, Nutrition and Nutraceuticals on Oral and Periodontal Health

“…In periodontal disease, pathogenic bacteria accumulated in the subgingival sulcus are the environmental factors that influence the inflammatory response of the periodontal tissues [16,17]. However, a central role of diet, natural agents and nutraceutics are also considered indirectly responsible for the health of periodontal tissues and against alveolar bone resorption [18][19][20][21][22].…”

Blockade of fatty acid signalling inhibits lipopolysaccharide‐induced macrophage recruitment and progression of apical periodontitis

“…Targeting CD36 through SSO treatment in mice attenuated high-fat diet-induced upregulation of NLRP3 inflammasome, IL-1b and IL-18 (Li et al 2018). Interestingly, CD36 was also implicated in the progression of periodontitis in mice (Lu et al 2017) and humans (Li et al 2019) with metabolic syndrome. The present findings further suggest that LPS-augmented CD36 signalling may also participate in the pathogenesis of apical periodontitis.…”

“…2017) and humans (Li et al . 2019) with metabolic syndrome. The present findings further suggest that LPS‐augmented CD36 signalling may also participate in the pathogenesis of apical periodontitis.…”