Introduction: The incidence of obesity has dramatically increased worldwide. Obesity has been shown to exacerbate the progression of periodontal disease. Studies suggest a sex difference in periodontitis, whereby males are more sensitive to periodontal inflammation compared to females. Aim: In the current study, it was hypothesized that obesity drives periodontal inflammation and bone loss in both sexes. Methodology: Utilizing leptin receptor mutant (SS^LepR mutant) rats as a genetic model of obesity, 11–12-week-old male and female lean Dahl salt-sensitive (SS) rats and obese SS^LepR mutant rats were used to investigate sex differences in obesity-induced periodontal inflammation. Results: Body weight, insulin, hemoglobin A1c and cholesterol levels were significantly elevated in the obese SS^LepR mutant strain vs. the lean SS strain within the same sex. Sex differences in body weight and plasma hemoglobin A1c were only observed in obese SS^LepR mutant rats, with males having significantly greater body weight and hemoglobin A1c vs. females. Plasma thiobarbituric acid reactive substances (TBARs) and monocyte chemoattractant protein-1 (MCP-1), markers of systemic oxidative stress and inflammation, respectively, were significantly elevated in obese SS^LepR mutant rats vs. lean SS rats, with no sex differences in these parameters in either rat strains. Although micro-CT analyses of the maxillary first molar alveolar bone from obese SS^LepR mutant rats revealed no evidence of bone loss and/or sex differences, immuno-histochemical analysis revealed significant elevations in periodontal IL-6 and decreases in IL-10 in obese SS^LepR mutant rats vs. lean SS rats, with no apparent sex differences in these parameters. Conclusions: Obesity increases systemic and periodontal inflammation, without evidence of bone loss or apparent sex differences in SS^LepR mutant rats.

Background: Obesity is a major contributor to chronic kidney disease (CKD) through mechanisms involving inflammation and metabolic dysregulation. Premenopausal female rats are known to be protected from cardiovascular disorders vs. age matched male rats. The current study investigates if there are sex differences in obesity-induced renal inflammation in SS leptin receptor mutant (SS^LepR mutant) rats as a model of metabolic syndrome. Method: Male and female lean and obese SS^LepR mutant rats were used in the current study to assess changes in metabolic parameters and markers of renal inflammation. Results: Obese SS^LepR rats showed significant increases in body weight, hemoglobin A1c (HbA1c), and cholesterol vs. lean control, although their blood glucose levels remained comparable to lean rats. Plasma leptin, insulin, and TNF-α converting enzyme (TACE) levels were significantly elevated in obese SS^LepR rats vs. lean control rats, with no apparent sex differences. Obesity was associated with an elevation in renal injury since protein and albumin excretion levels were significantly elevated in obese SS^LepR rats vs. lean control rats, with no apparent sex differences. The elevation in renal injury was associated with increased renal fibrosis as evidenced by increased collagen deposition and TGF-β expression in the kidney of obese SS^LepR rats vs. lean control rats. Increased renal fibrosis also coincided with increased renal inflammation and apoptosis as evidenced by increased macrophage infiltration and IL-6 expression in the kidneys of obese SS^LepR rats vs. lean control rats. Conclusion: These findings indicate that obesity triggers renal inflammation and fibrosis independent of hyperglycemia in SS^LepR rats, and these changes may override sex-based protective effects seen in females in other experimental rodent models of cardiovascular diseases.