Activation of GPR120 involved in the anti-inflammatory response and alleviation of apoptosis in sepsis-associated acute kidney injury

Background Current treatments for sepsis-associated acute kidney injury (S-AKI) lack specificity and urgently need novel therapeutic targets. G-protein-coupled receptor 120 (GPR120) has exerted anti-inflammatory and anti-apoptotic effects across multiple cells, however, the specific role of GPR120 in the pathogenesis of S-AKI has not been thoroughly investigated. Materials and Methods S-AKI models were established in wild-type (WT) and Gpr120 ^−/− mice via lipopolysaccharide (LPS) injection. Mice were orally pretreated with docosahexaenoic acid (DHA) for 14 days before LPS injection. Eighteen hours after LPS administration, renal function, inflammatory markers, and apoptosis were assessed through biochemical assays, histological analysis, and western blotting. Results LPS exposure significantly decreased survival rates and elevated serum creatinine and blood urea nitrogen (BUN) levels in S-AKI mice. DHA pretreatment ameliorated these effects by activating GPR120. This activation also reduced the expression of IL-6, TNF-α, and IL-1β at both the gene and protein levels, accompanied by decreased phosphorylation of NF-κB and JNK signaling pathways. Furthermore, GPR120 activation diminished the number of TUNEL-positive cells and cleaved caspase-3 in renal tissues. In contrast, Gpr120 ^−/− mice exhibited aggravated renal dysfunction, inflammation, and apoptosis following LPS challenge. Conclusions Activation of GPR120 by DHA alleviates inflammation and apoptosis, underscoring its novel therapeutic potential for S-AKI.