Circulating insulin-like growth factor system adaptations in hibernating brown bears indicate increased tissue IGF...

Area of Science:

• Comparative Physiology
• Endocrinology
• Molecular Biology

Background:

• Brown bears maintain muscle and bone mass during prolonged hibernation.
• Understanding hibernation's molecular mechanisms could yield therapeutic insights for humans.
• Insulin-like growth factors (IGFs) are hypothesized to play a role in tissue preservation during hibernation.

Purpose of the Study:

• To investigate the role of IGFs and their binding proteins in brown bear tissue conservation during hibernation.
• To determine if altered IGF bioavailability contributes to preserving muscle and bone mass.
• To explore the potential therapeutic relevance of hibernation-related molecular changes.

Main Methods:

• Measured plasma levels of IGF-1, IGF-2, and IGF-binding proteins (IGFBPs) in active and hibernating bears.
• Analyzed liver mRNA expression of IGF-1, IGFBP-2, IGFBP-3, and acid-labile subunit (ALS).
• Utilized size-exclusion chromatography to assess IGF complex distribution and homology modeling for IGF-2 variant analysis.

Main Results:

• Plasma IGF-1 and IGF-2 levels were reduced during hibernation, but IGFBP-2 became codominant.
• Circulating ALS levels and ternary IGF/IGFBP/ALS complexes decreased, shifting towards smaller binary IGF/IGFBP complexes.
• A unique IGF-2 splice variant, potentially enhancing bone-specific targeting, was identified in hibernating bears.

Conclusions:

• Hibernating bears increase IGF tissue availability by shifting to binary IGF/IGFBP complexes.
• A specific IGF-2 splice variant may contribute to bone-specific anabolic signaling and tissue preservation.
• These findings suggest that IGF bioavailability and targeted delivery are key to tissue conservation during hibernation.