C3ar1, the gene encoding the complement receptor C3a receptor 1, is involved in the complement system, which plays pleiotropic roles in metabolic homeostasis, organismal energy balance, and the immune response. C3a, produced upon complement activation, binds to C3aR1 to mediate inflammation [5]. Genetic models, such as knockout (KO) and conditional knockout (CKO) mouse models, have been crucial for studying C3ar1's function.

In β cells, β-C3aR1 KO mice exhibit worse glucose tolerance, lower insulin levels, decreased β cell mass, and impaired insulin secretion. This indicates C3aR1 is essential for maintaining β cell homeostasis, especially under obesity and type 2 diabetes (T2D) duress [1,6].

In Tregs, C3ar1-/-C5ar1-/-Foxp3+ cells show enhanced Treg stability through increased suppressor of cytokine signaling 1/2/3, vitamin C stabilization, and ten-eleven translocation 1, 2, 3 expression [2].

Male adipocyte-specific C3aR1-knockout mice display enhanced white adipose tissue (WAT) thermogenesis, while female counterparts have decreased brown fat thermogenesis, revealing sexual dimorphism in the adipsin/C3a/C3aR1 axis in regulating adipose thermogenesis [3].

In cancer, blocking the C3-C3AR1 axis in gastric cancer peritoneal metastases disrupts stroma-myeloid crosstalk and improves immune checkpoint blockade benefits [4].

In pain models, C3aR1 KO mice have less severe paclitaxel-induced mechanical allodynia, suggesting C3aR1 is involved in this pain syndrome [5].

In summary, C3ar1 plays diverse and vital roles in maintaining normal physiological functions in various tissues and is associated with multiple disease conditions, including T2D, adipose-related metabolic disorders, cancer, and chemotherapy-induced neuropathic pain. The use of KO/CKO mouse models has significantly advanced our understanding of C3ar1's function in these biological processes and disease areas.