Exogenous IGF-1 improves cognitive function in rats with high-fat diet consumption

Area of Science:

• Neuroscience
• Molecular Biology
• Endocrinology

Background:

• Insulin-like growth factor-1 (IGF-1) is known to improve cognitive function, but its precise mechanism remains unclear.
• High-fat diets can induce cognitive deficits and anxiety behaviors, often linked to inflammation and oxidative stress.
• The PI3K/Akt/CREB signaling pathway plays a crucial role in neuronal survival, plasticity, and cognitive processes.

Purpose of the Study:

• To investigate whether IGF-1's protective effects on cognitive function and anxiety in high-fat diet rats are mediated by the PI3K/Akt/CREB pathway.
• To explore the impact of IGF-1 on inflammation and oxidative stress markers in the hippocampus of rats fed a high-fat diet.

Main Methods:

• Neuronal cells (HT22) were treated with IGF-1 and pathway inhibitors (LY294002, 666-15) to assess protein expression via Western blot.
• Rats were fed a high-fat diet and treated with IGF-1 or IGF-1 combined with pathway inhibitors.
• Cognitive function and anxiety were evaluated using the Morris water maze and open field tests, respectively. Biomarkers for inflammation and oxidative stress were measured.

Main Results:

• IGF-1 treatment increased p-PI3K, p-Akt, and p-CREB expression in neuronal cells. Inhibitors reduced these levels.
• High-fat diet rats exhibited impaired cognitive function, increased anxiety, reduced PI3K/Akt/CREB pathway activity, and elevated oxidative stress and inflammation.
• IGF-1 administration reversed these detrimental effects, while pathway inhibitors attenuated IGF-1's protective benefits.

Conclusions:

• IGF-1 administration improves cognitive function and anxiety-like behavior in rats subjected to a high-fat diet.
• The neuroprotective effects of IGF-1 are mediated through the activation of the PI3K/Akt/CREB signaling pathway.
• IGF-1 also mitigates inflammation and oxidative stress in the hippocampus, contributing to its beneficial outcomes.