The role of FNDC5/Irisin in brain energy metabolism in models of Alzheimer’s Disease

Abstract Background Alzheimer’s disease (AD) brains present defective metabolic profiles that are associated with amyloid‐β (Aβ) accumulation. We have previously shown that physical exercise promotes the expression of FNDC5/irisin, which in turn acts in the brain to trigger neuroprotection in AD models. Here, we investigated whether irisin rescues defective mitochondrial function induced by Aβ oligomers (AβOs). Method Hippocampal slices from 4‐month‐old wild‐type C57BL/6J mice were prepared and exposed to AβOs (1 µM) in the presence or absence of recombinant irisin (25 nM) for 3 h. We assessed levels of proteins related to mitochondrial fusion (MFN1, OPA1) and fission (DRP1) by Western blotting and mitochondrial function, by high‐resolution respirometry. Biochemical assays were used to determine glucose uptake, lactate content and NAD levels. Results Acute exposure to AβOs or irisin did not trigger any significant changes in proteins associated with mitochondrial dynamics or the amount of lactate released after AβOs exposure. Initial results indicate that irisin prevents the variations caused by AβOs in NAD + levels and glucose uptake in hippocampal slices. Slices exposed to AβOs show a trend of reduction in ATP synthesis‐, complexes II/III‐coupled O 2 and in residual O 2 consumption. Treatment with irisin seems to prevent these events. Conclusion Irisin seems to preserve against the impact of AβOs on selective mitochondrial properties in the hippocampus. Future studies will further elucidate the mechanisms by which irisin is neuroprotective in AD mice.