Saa1, short for Serum amyloid A1, is a lipid-binding protein and an important regulator in inflammation [2,3]. It is also involved in maintaining glucose and lipid homeostasis [1]. Saa1 proteins are lipophilic and contribute to high-density lipoproteins and cholesterol transport, and interact with specific receptors, being implicated in various biological processes like tissue remodeling, cancer metastasis, and inflammation-related diseases [2].

In a study on cardiac remodeling, Saa1-deficient (SAA1-/-) mice exposed to transverse aortic banding surgery showed a lower level of cardiac fibrosis compared to wild-type mice after 8 weeks, indicating that Saa1 absence hinders cardiac fibrosis likely by inhibiting NF-κB/p38/JNK and TGFβ/Smad pathways [3]. In the context of non-alcoholic fatty liver disease (NAFLD), knockout of SAA1/2 or knockdown of hepatic SAA1/2 in mice fed a high-fat diet promoted energy expenditure and alleviated metabolic disorder, hepatic steatosis, and inflammation. Conversely, endogenous overexpression of Saa1 in hepatocytes aggravated these conditions, and this was alleviated by knockout of toll-like receptor 4 (TLR4), suggesting Saa1 forms a SAA1/TLR4/NF-κB/SAA1 feedforward regulatory circuit to trigger hepatic steatosis and intra-hepatic inflammation [4].

In conclusion, Saa1 is significantly involved in inflammation-related biological processes. Studies using Saa1 knockout mouse models have revealed its role in cardiac remodeling and NAFLD, providing insights into the disease mechanisms and potential therapeutic targets in these disease areas.