Year: 2023
Type: preprint
Abstract: Summary The metabolite 2-hydroxybutyrate (2HB) is produced by skeletal muscle acutely during exercise and persists for several hours in the blood post-exertion. We show here that 2HB directly inhibits branched- chain aminotransferase enzymes, and that this inhibition in turn triggers a SIRT4-dependent shift in the compartmental abundance of protein ADP-ribosylation. The 2HB-induced decrease in nuclear protein ADP-ribosylation leads to a C/EBPβ mediated transcriptional response in the branched-chain amino acid degradation pathway. This response to 2HB exposure leads to an improved oxidative capacity both in vitro and in vivo, with the latter mimicking the effects of exercise training on whole body metabolism. Thus, we show here that 2-HB production by skeletal muscle represents a novel mechanism for the modification of metabolism by exercise.
Source: eLife
Institutions: Karolinska Institutet, University of Cambridge, University of Oulu
Language: English
Subfield: Geriatrics and Gerontology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,500
Awards: G277072494, Förbättring av immunterapi genom manipulering av metabolism, Increasing immunotherapeutic efficacy through manipulation of hypoxic response, Título novo: The role of hypoxia in T cell function and immunotherapy. Título inicial: Vascular endothelium: fit for purpose - understanding the molecular basis for organ-specific regulation of vascular (dys)function, G4313044806, G4695473640
OpenAlex ID: W4388971726