HFD_VV_AKI_Supplemental Figures

Climate change is increasing <i>Vibrio vulnificus</i> infections, while rising obesity rates heighten vulnerability to severe bacterial infections. Obesity and high-fat diet (HFD) intake promote inflammation and immune imbalance, potentially worsening sepsis and acute kidney injury (AKI). This study examined how HFD-induced metabolic dysfunction contributes to <i>V. vulnificus</i>-associated AKI. C57BL/6J mice were fed CHOW or 60% kcal HFD for six weeks before intragastric <i>V. vulnificus</i> infection. Kidney function and tissue markers of inflammation, oxidative stress, and necrosis were analyzed, along with systemic Th17/Treg ratios. In vitro, renal epithelial cells were treated with leptin and IL-17A ± IL-17 receptor antagonist. Results showed that HFD + <i>V. vulnificus</i> infection led to increased Th17/Treg imbalance, renal TLR4 activation, and inflammation. In vitro, leptin and IL-17 synergistically activated NF-κB and cytokine release. These findings suggest that metabolic stress amplifies renal injury through IL-17–leptin interactions, highlighting potential therapeutic targets to mitigate AKI in obese individuals with sepsis.