Muscle-building supplement β-hydroxy β-methylbutyrate binds to PPARα to improve hippocampal functions in mice.
| Autor: | Paidi RK; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA., Raha S; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA., Roy A; Simmaron Research Institute, Technology Innovation Center, 10437 W Innovation Drive, Wauwatosa, WI, USA., Pahan K; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA; Division of Research and Development, Jesse Brown Veterans Affairs Medical Center, Chicago, IL, USA. Electronic address: kalipada_pahan@rush.edu. |
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| Jazyk: | angličtina |
| Zdroj: | Cell reports [Cell Rep] 2023 Jul 25; Vol. 42 (7), pp. 112717. Date of Electronic Publication: 2023 Jul 11. |
| DOI: | 10.1016/j.celrep.2023.112717 |
| Abstrakt: | This study underlines the importance of β-hydroxy β-methylbutyrate (HMB), a muscle-building supplement in human, in increasing mouse hippocampal plasticity. Detailed proteomic analyses reveal that HMB serves as a ligand of peroxisome proliferator-activated receptor α (PPARα), a nuclear hormone receptor involved in fat metabolism, via interaction with the Y314 residue. Accordingly, HMB is ineffective in increasing plasticity of PPARα -/- hippocampal neurons. While lentiviral establishment of full-length PPARα restores the plasticity-promoting effect of HMB in PPARα -/- hippocampal neurons, lentiviral transduction of Y314D-PPARα remains unable to do that, highlighting the importance of HMB's interaction with the Y314 residue. Additionally, oral HMB improves spatial learning and memory and reduces plaque load in 5X familial Alzheimer's disease (5XFAD) mice, but not in 5XFAD ΔPPARα mice (5XFAD lacking PPARα), indicating the involvement of PPARα in HMB-mediated neuroprotection in 5XFAD mice. These results delineate neuroprotective functions of HMB and suggest that this widely used supplement may be repurposed for AD. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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