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  • The Influence of Acute Beta-Hy...

Treffer: The Influence of Acute Beta-Hydroxy Beta-Methylbutyrate (HMB) Ingestion on the Human Skeletal Muscle Transcriptome.

Title:
The Influence of Acute Beta-Hydroxy Beta-Methylbutyrate (HMB) Ingestion on the Human Skeletal Muscle Transcriptome.
Authors:
Wilkinson DJ; Centre of Metabolism, Ageing & Physiology, National Institute of Health Research (NIHR) Biomedical Research Centre (BRC), University of Nottingham, Nottingham NG7 2RD, UK., Gallagher IJ; Centre for Biomedicine & Global Health, Napier University, Edinburgh EH11 4BN, UK., Crossland H; Centre of Metabolism, Ageing & Physiology, National Institute of Health Research (NIHR) Biomedical Research Centre (BRC), University of Nottingham, Nottingham NG7 2RD, UK., Pereira SL; Abbott Nutrition, Columbus, OH 43219, USA., Rueda R; Abbott Nutrition, 18004 Granada, Spain., Phillips BE; Centre of Metabolism, Ageing & Physiology, National Institute of Health Research (NIHR) Biomedical Research Centre (BRC), University of Nottingham, Nottingham NG7 2RD, UK., Smith K; Centre of Metabolism, Ageing & Physiology, National Institute of Health Research (NIHR) Biomedical Research Centre (BRC), University of Nottingham, Nottingham NG7 2RD, UK., Deane CS; Human Development & Health, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.; National Institute of Health Research (NIHR) Southampton Biomedical Research Centre (BRC), University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton SO16 6YD, UK., Atherton PJ; Centre of Metabolism, Ageing & Physiology, National Institute of Health Research (NIHR) Biomedical Research Centre (BRC), University of Nottingham, Nottingham NG7 2RD, UK.; Faculty of Sport and Health Science, Ritsumeikan Advanced Research Academy (RARA), Ritsumeikan University, Kyoto 525-8577, Japan.
Source:
Nutrients [Nutrients] 2026 Jan 28; Vol. 18 (3). Date of Electronic Publication: 2026 Jan 28.
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: MDPI Publishing Country of Publication: Switzerland NLM ID: 101521595 Publication Model: Electronic Cited Medium: Internet ISSN: 2072-6643 (Electronic) Linking ISSN: 20726643 NLM ISO Abbreviation: Nutrients Subsets: MEDLINE
Imprint Name(s):
Original Publication: Basel, Switzerland : MDPI Publishing
MeSH Terms:
Valerates*/administration & dosage , Valerates*/pharmacology , Transcriptome*/drug effects , Muscle, Skeletal*/metabolism , Muscle, Skeletal*/drug effects, Muscle Proteins/metabolism ; Muscle Proteins/genetics ; Humans ; Male ; Young Adult ; Adult
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Grant Information:
0 Abbott Nutrition (United States)
Contributed Indexing:
Keywords: RNA sequencing; amino acid transporters; beta-hydroxy beta-methylbutyrate (HMB); circadian rhythm; inflammation; skeletal muscle; transcriptome
Substance Nomenclature:
0 (Valerates)
3F752311CD (beta-hydroxyisovaleric acid)
0 (Muscle Proteins)
Entry Date(s):
Date Created: 20260213 Date Completed: 20260213 Latest Revision: 20260216
Update Code:
20260216
PubMed Central ID:
PMC12899265
DOI:
10.3390/nu18030434
PMID:
41683256
Database:
MEDLINE

Weitere Informationen

Background: Nutritional interventions to mitigate age/disease-related skeletal muscle attrition are much needed given the growing older population. Beta-hydroxy beta-methylbutyrate (HMB), an endogenous metabolite of the essential amino acid leucine, has anabolic properties in skeletal muscle: acutely stimulating muscle protein synthesis and attenuating muscle protein breakdown. While the role of supplemental HMB on muscle protein turnover is established, mechanistic effects on the muscle transcriptome have not been examined. Methods: Total RNA was extracted from m. vastus lateralis muscle biopsies of young males (n = 14) before and ~2.5 h after oral consumption of ~3 g HMB. Global changes in the muscle transcriptome were assessed via RNA sequencing, and differential expression in genes between fasted and 'fed' (HMB) conditions was determined. To identify the functional biology of differentially expressed genes, gene set enrichment and active subnetwork-orientated enrichment analyses was performed. Results: Of 15,982 genes detected, 468 were significantly upregulated and 326 were significantly downregulated in response to HMB. These genes were found to be associated with molecular pathways regulating muscle protein turnover, most notably, JAK-STAT signalling (e.g., STAM), circadian rhythm (e.g., NR1D1, NR1D2, PER2, PER3), TNFα signalling (e.g., TNFRSF1A, CCL2, CXCL2), and protein synthesis (e.g., POLR1A, POLR2A, POLR3A, PIK3RR, SGK1). HMB also regulated the expression of AA transporters, evoking a robust increase in SLC36A1 (PAT1) and SLC7A5 (LAT1). Conclusions: HMB evokes transcriptional events important in the homeostasis of muscle, supporting a role in proteostasis and one akin to protein intake, i.e., upregulation of AA transporters. Future work should further define HMB's transcriptomic/proteomic effects in ageing/disease and synergy with exercise.