TNF and obesity due to melanocortin 4 receptor deficiency: As a product of the gut microbiota, the increased LPS in serum and synovial fluid of HFD-induced obesity rats also provided a link between the associations measured between gut microbes, chronic inflammation, and increased joint damage, because LPS participated in activating macrophages in arthrodial cartilage of obesity rats, through stimulating toll-like receptor (TLR) 2/4 and activating the NF-κB signaling pathway, subsequently promoting the secretion of proinflammatory mediators such as TNF-α [48].