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basmwklz OP t1_j3kixdx wrote

Abstract: >Little is known about the impact of metabolic stimuli on brain tissue at a molecular level. The ketone body beta-hydroxybutyrate (BHB) can be a signaling molecule regulating gene transcription. Thus, we assessed lysine beta-hydroxybutyrylation (K-bhb) levels in proteins extracted from the cerebral cortex of mice undergoing a ketogenic metabolic challenge (48 h fasting). We found that fasting enhanced K-bhb in a variety of proteins including histone H3. ChIP-seq experiments showed that K9 beta-hydroxybutyrylation of H3 (H3K9-bhb) was significantly enriched by fasting on more than 8000 DNA loci. Transcriptomic analysis showed that H3K9-bhb on enhancers and promoters correlated with active gene expression. One of the most enriched functional annotations both at the epigenetic and transcriptional level was “circadian rhythms''. Indeed, we found that the diurnal oscillation of specific transcripts was modulated by fasting at distinct zeitgeber times both in the cortex and suprachiasmatic nucleus. Moreover, specific changes in locomotor activity daily features were observed during re-feeding after 48-h fasting. Thus, our results suggest that fasting remarkably impinges on the cerebral cortex transcriptional and epigenetic landscape, and BHB acts as a powerful epigenetic molecule in the brain through direct and specific histone marks remodeling in neural tissue cells.


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Zarkdiaz t1_j3kn1as wrote

How similar is BHB to the drug GHB?


MethylSamsaradrolone t1_j3kr6b5 wrote

Despite their names, not similar at all apart from both affecting metabolic functions in some way.

BHB is a well-tolerated supplement with no significant psychoactive effects. Afaik at least.


doctoreldritch t1_j3ksu3p wrote

Structurally very similar, one has an OH group on the 2nd-to-last carbon, the other instead has it on the very last carbon in the chain. Chemically pretty similar as well. But biologically not very similar at all, because enzymes are extremely shape-specific.