Repressed FABP5 expression or activity weakens the adaptive response to AKI

In vitro, FABP5 activity was pharmacologically inhibited, after which lipid storage, degradation, and cellular stress events leading to cell death were assessed. In vivo, the role of FABP5 was evaluated by comparing FABP5-deficient mice subjected to folic acid–induced AKI (FA-AKI) with wild-type mice, as well as in wild-type mice treated with a pharmacological FABP5 inhibitor. The involvement of FABP5 in FA-AKI was first explored through renal transcriptomic analysis and subsequently validated by biochemical assessment of renal function and injury markers.

FABP5 expression was found to be significantly reduced in the FA-AKI model. Inhibition of FABP5 activity in renal tubular cells led to increased cellular stress, characterised by depletion of lipid droplets, impaired fatty acid delivery to mitochondria, reduced ATP levels, oxidative stress, mitochondrial loss, and cell death. Consistently, both genetic deletion and pharmacological inhibition of FABP5 aggravated the initial phase of the disease.

These results demonstrate that FABP5 instability represents an important maladaptive mechanism during AKI. Therefore, preservation of FABP5 may confer resilience to AKI.