Moreover, RES alleviated inflammation and minimized bodyweight in KOA mice via the TLR4/NF-kB pathway in a high-fat diet (HFD)-induced obesity-associated KOA mouse model (Jiang et al., 2017; Xu et al., 2019; Long et al., 2021). Here, TLR4 is linked to obesity due to melanocortin 4 receptor deficiency.