Circulating insulin-like growth factor system adaptations in hibernating brown bears indicate increased tissue IGF availability
| Autor: | Anne Mette Frøbert, Malene Brohus, Tinna S. Roesen, Jonas Kindberg, Ole Fröbert, Cheryl A. Conover, Michael T. Overgaard |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Physiology
Endocrinology Diabetes and Metabolism Insulin-Like Growth Factor Binding Proteins/metabolism acid labile subunit (ALS) Insulin-Like Growth Factor Binding Protein 2/metabolism IGF-binding protein (IGFBP) insulin-like growth factor (IGF) Ursus arctos Ursidae/metabolism Insulin-Like Growth Factor Binding Proteins Insulin-Like Growth Factor Binding Protein 2 Insulin-Like Growth Factor II/metabolism Insulin-Like Growth Factor Binding Protein 3 Insulin-Like Growth Factor I/metabolism Insulin-Like Growth Factor II Physiology (medical) Insulin-Like Growth Factor Binding Protein 3/metabolism Animals Insulin-Like Growth Factor I hibernation Ursidae |
| Zdroj: | Frøbert, A M, Brohus, M, Roesen, T S, Kindberg, J, Fröbert, O, Conover, C A & Overgaard, M T 2022, ' Circulating insulin-like growth factor system adaptations in hibernating brown bears indicate increased tissue IGF availability ', American Journal of Physiology-Endocrinology and Metabolism, vol. 323, no. 3, pp. E307-E318 . https://doi.org/10.1152/ajpendo.00429.2021 Frøbert, A M, Brohus, M, Roesen, T S, Kindberg, J, Fröbert, O, Conover, C A & Overgaard, M T 2022, ' Circulating insulin-like growth factor system adaptations in hibernating brown bears indicate increased tissue IGF availability ', American Journal of Physiology: Endocrinology and Metabolism, vol. 323, no. 3, pp. E307-E318 . https://doi.org/10.1152/ajpendo.00429.2021 |
| DOI: | 10.1152/ajpendo.00429.2021 |
| Popis: | Brown bears conserve muscle and bone mass during 6 mo of inactive hibernation. The molecular mechanisms underlying hibernation physiology may have translational relevance for human therapeutics. We hypothesize that protective mechanisms involve increased tissue availability of insulin-like growth factors (IGFs). In subadult Scandinavian brown bears, we observed that mean plasma IGF-1 and IGF-2 levels during hibernation were reduced to 36 ± 10% and 56 ± 15%, respectively, compared with the active state (n = 12). Western ligand blotting identified IGF-binding protein (IGFBP)-3 as the major IGFBP in the active state, whereas IGFBP-2 was codominant during hibernation. Acid labile subunit (ALS) levels in hibernation were reduced to 41±16% compared with the active state (n = 6). Analysis of available grizzly bear RNA sequencing data revealed unaltered liver mRNA IGF-1, IGFBP- 2, and IGFBP-3 levels, whereas ALS levels were significantly reduced during hibernation (n = 6). Reduced ALS synthesis and circulating levels during hibernation should prompt a shift from ternary IGF/IGFBP/ALS to smaller binary IGF/IGFBP complexes, thereby increasing IGF tissue availability. Indeed, size-exclusion chromatography of bear plasma demonstrated a shift to lower molecular weight IGF-containing complexes in the hibernating versus the active state. Furthermore, we note that the major IGF-2 mRNA isoform expressed in livers in both Scandinavian brown bears and grizzly bears was an alternative splice variant in which Ser29 is replaced with a tetrapeptide possessing a positively charged Arg residue. Homology modeling of the bear IGF-2/ IGFBP-2 complex showed the tetrapeptide in proximity to the heparin-binding domain involved in bone-specific targeting of this complex. In conclusion, this study provides data which suggest that increased IGF tissue availability combined with tissue-specific targeting contribute to tissue preservation in hibernating bears. |
| Databáze: | OpenAIRE |
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