BACKGROUND: Insulin signaling and Tau protein phosphorylation in the hippocampi of young and old obese Zucker fa/fa rats and their lean controls were assessed to determine whether obesity-induced peripheral insulin resistance and aging are risk factors for central insulin resistance and whether central insulin resistance is related to the pathologic phosphorylation of the Tau protein. RESULTS: Aging and obesity significantly attenuated the phosphorylation of the insulin cascade kinases Akt (protein kinase B, PKB) and GSK-3β (glycogen synthase kinase 3β) in the hippocampi of the fa/fa rats. Furthermore, the hyperphosphorylation of Tau Ser396 alone and both Tau Ser396 and Thr231 was significantly augmented by aging and obesity, respectively, in the hippocampi of these rats. CONCLUSIONS: Both age-induced and obesity-induced peripheral insulin resistance are associated with central insulin resistance that is linked to hyperTau phosphorylation. Peripheral hyperinsulinemia, rather than hyperglycemia, appears to promote central insulin resistance and the Tau pathology in fa/fa rats.

Institute of Organic Chemistry and Biochemistry Prague 166 10 Czech Republic

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Metabolomic Study of Aging in fa/fa Rats: Multiplatform Urine and Serum Analysis

Palmitoylated prolactin-releasing peptide treatment had neuroprotective but not anti-obesity effect in fa/fa rats with leptin signaling disturbances

Aging and high-fat diet feeding lead to peripheral insulin resistance and sex-dependent changes in brain of mouse model of tau pathology THY-Tau22