The effects of a High-Fat Diet and High-Intensity Interval Training on SIRT۱ Protein Expression in the Hippocampus of Adult Male C۵۷ Mice.

High‑fat diets (HFD) impair hippocampal function by disrupting molecular pathways involved in synaptic plasticity and memory, particularly through the downregulation of Sirtuin‑۱ (SIRT۱), an NAD⁺‑dependent regulator of mitochondrial function and neuronal protection. Conversely, high‑intensity interval training (HIIT) may enhance neuroplasticity and cerebral energy metabolism through activation of the AMPK–SIRT۱–PGC‑۱α signaling pathway, although its effectiveness under HFD conditions remains unclear. This study examined the effects of six weeks of HIIT, with or without HFD, on hippocampal SIRT۱ protein levels in adult male C۵۷ mice. Twenty mice were randomly assigned to four groups (control, HFD, HIIT, HIIT+HFD; n=۵ per group). The HIIT protocol consisted of six ۴‑min treadmill running bouts at ۲۲ m/min separated by ۲‑min active recovery periods, including standardized warm‑up and cool‑down phases. Hippocampal SIRT۱ expression was measured by Western blot and normalized to β‑actin. Statistical analysis (Shapiro–Wilk, one‑way ANOVA, Tukey’s HSD; p<۰.۰۵) revealed significant group differences (p<۰.۰۰۱). The HFD group showed the lowest SIRT۱ expression, whereas the HIIT group exhibited the highest levels. Although HIIT combined with HFD produced a modest (~۱۲%) increase compared with HFD alone, this effect was not statistically significant. These findings indicate that HFD suppresses hippocampal SIRT۱ expression and may impair synaptic plasticity, while HIIT promotes a neuroprotective molecular profile. However, the beneficial effects of HIIT appear attenuated under HFD conditions, suggesting that metabolic stressors such as reduced NAD⁺ availability and neuroinflammation may limit exercise‑induced molecular adaptations. Therefore, combining exercise interventions with dietary regulation may be essential for restoring optimal hippocampal plasticity and cognitive function.

کلیدواژه ها:

High‑fat diet (HFD) ، High‑intensity interval training (HIIT) ، SIRT۱ ، Hippocampus ، Neuroplasticity ، AMPK–SIRT۱–PGC‑۱α pathway ، Cognitive function