| First Author | Paidi RK | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 7 | Pages | 112717 |
| PubMed ID | 37437568 | Mgi Jnum | J:339131 |
| Mgi Id | MGI:7516264 | Doi | 10.1016/j.celrep.2023.112717 |
| Citation | Paidi RK, et al. (2023) Muscle-building supplement beta-hydroxy beta-methylbutyrate binds to PPARalpha to improve hippocampal functions in mice. Cell Rep 42(7):112717 |
| abstractText | This study underlines the importance of beta-hydroxy beta-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 alpha (PPARalpha), a nuclear hormone receptor involved in fat metabolism, via interaction with the Y314 residue. Accordingly, HMB is ineffective in increasing plasticity of PPARalpha(-/-) hippocampal neurons. While lentiviral establishment of full-length PPARalpha restores the plasticity-promoting effect of HMB in PPARalpha(-/-) hippocampal neurons, lentiviral transduction of Y314D-PPARalpha 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(DeltaPPARalpha) mice (5XFAD lacking PPARalpha), indicating the involvement of PPARalpha 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. |
