## 4 Discussion
Both increased and decreased adiponectin levels correlating with obesity have been reported. Moreover, the controversy of adiponectin's effect on systemic chronic inflammation and joint inflammation is still a matter of debate [48]. Our study revealed that adiponectin was less sensitive in responding to the increased bodyweight or body fat, but ovariectomy significantly elevated adiponectin. Increased adiponectin can induce NOS2, IL-6, MMP-3, MMP-9, and MCP-1 expression in chondrocytes [49], influencing the pathophysiology of osteoarthritis. Theoretically, low-grade inflammation in obesity is characterized by a systemic influx of adipokines (leptin, adiponectin, and resistin) and an increase of proinflammatory cytokines (IL-1\(\beta\), IL-6, TNF-\(\alpha\), and MCP-1) in small quantities, and thus linked to many chronic inflammation diseases [50; 51]. In one published study, rats fed high fat and high carbohydrate diets were shown to have significantly increased serum IFN-\(\gamma\) and IL-1\(\beta\), and decreased serum IL-10, concurrent with synovitis and cartilage destruction [17]. [PERSON] et al. 's [16] study, on the other hand, showed that serum IFN-\(\gamma\), II-10, IL-12, IL-13, IL-17a, IL-18, IL-19, IL-2, IL-6 TNF-\(\alpha\), and MCP-1 were not significantly different between diet-induced obese rats and normal-diet fed rats; however, most of the proinflammatory cytokines were elevated in synovial fluid and related to joint pathological lesions. It is possible that low-grade inflammation might be obscured at the systemic level but is definitively altering immune responses at local tissue or cellular function levels [52]. The evidence showed that activation of macrophage functions at local tissue such as synovial membrane is related to OA or rheumatoid arthritis [53]. Our results concurred with this previous work. We did not see modulation of proinflammatory cytokines in plasma in response to HFHS, and only increased plasma MCP-1 was detected in response to ovariectomy. MCP-1, a chemokine produced by adipocytes, macrophages, and endothelial cells, can regulate macrophage polarization and infiltration, insulin sensitivity, and lipid metabolism [54]. Therefore, it causes local inflammation such as arteriosclerosis and coronary heart disease [55] or probably osteoarthritis. Interestingly, plasma MCP-1 theoretically is associated with adiposity [56], but our data revealed that MCP-1 was modified by the effect of ovariectomy, not obesity. The male rats in [PERSON]'s study [16] gained even more weight than our female rats, but no change of plasma MCP-1 levels was detected. This evidence indicates that MCP-1 is distinctly different in females and might be a crucial modulator of MetOA in post-menopausal women; if so, then it could be used as a biomarker to diagnose or monitor disease progression in this population. It may also be of interest to determine whether drugs that target MCP-1 are more potent against this specific OA phenotype. Further, the change in plasma IL-17 influenced by the interaction effect between GSM and OVX was irrelevant to other results. IL-17 is recognized as a T cell activator of neutrophil mobilization and activation, mediating innate immunity and being involved with the pathogenesis of inflammatory diseases such as psoriasis and rheumatoid arthritis [57]. Therefore, IL-17 would have been expected to increase in the OVX rat fed HFHS, which showed pathological joints. However, a previous study revealed no relation of IL-17 to HFHS diets [16]. Despite a lack of explanation to this occurrence, we speculate that this change may be related to an alteration of gut microbiota due to GSM and OVX, or possibly an as-yet unexplored interaction between GSM, diet, and estrogen levels. Menopause is a critical factor of osteoarthritis in women, changing the low prevalence of female at age under 50 years old to a prevalence greater than males after the postmenopausal period [3]. The result at the end of this study showed that average BMD in OVX rats was 10% lower than sham rats in all bone sites.