Propranolol normalizes metabolomic signatures thereby improving outcomes after burn

Abstract

Objective and Summary Background Data: Propranolol, a non-selective beta receptor blocker, improves outcomes of severely burned patients. While the clinical and physiological benefits of beta blockade are well characterized, the underlying metabolic mechanisms are less well defined. We hypothesized that propranolol improves outcomes after burn injury by profoundly modulating metabolic pathways. Methods: In this phase II randomized controlled trial, patients with burns ≥20% of total body surface area were randomly assigned to control or propranolol (dose given to decrease heart rate <100 bpm). Outcomes included clinical markers, inflammatory and lipidomic profiles, untargeted metabolomics, and molecular pathways. Results: Fifty-two severely burned patients were enrolled in this trial (propranolol n=23 and controls n=29). There were no significant differences in demographics or injury severity between groups. Metabolomic pathway analyses of the adipose tissue showed that propranolol substantially alters several essential metabolic pathways involved in energy and nucleotide metabolism, as well as catecholamine degradation (P<0.05). Lipidomic analysis revealed that propranolol-treated patients had lower levels of pro-inflammatory palmitic acid (P<0.05) and saturated fatty acids (P<0.05) with an increased ratio of polyunsaturated fatty acids (P<0.05), thus shifting the lipidomic profile towards an anti-inflammatory phenotype after burn (P<0.05). These metabolic effects were mediated by decreased activation of hormone-sensitive lipase at serine 660 (P<0.05) and significantly reduced ER stress by decreasing p-JNK (P<0.05). Conclusions: Propranolol’s ability to mitigate pathophysiological changes to essential metabolic pathways results in significantly improved stress responses.

1H-nuclear magnetic resonance analysis reveals dynamic changes in the metabolic profile of patients with severe burns

“…This study employed longitudinal observations of the metabolic products of critically burned patients and, for the first time, conducted a combined analysis of the acquired differentially abundant metabolites with the burn course, elucidating certain metabolites that exhibit regular changes concomitant with the burn duration. Although the incorporation of temporal factors yielded a relatively diminished number of metabolites in comparison to that in the existent literature [ 42 , 49 ], this study provides profound insights into the dynamic alterations in metabolic processes postburn. Therefore, the delineation of burn metabolic profiles has important value in obtaining a comprehensive grasp of the overarching patterns of burn-related metabolic processes.…”

Hydrogen-Rich Gas Enhanced Sprint-Interval Performance: Metabolomic Insights into Underlying Mechanisms

“…Metabonomics technology has the ability of acquiring high throughput "snapshots" of a whole organism's metabolic status [12][13][14], providing comprehensive insights into the mechanism underneath the regulation of functional performance by analyzing changes in endogenous metabolites during exercise [15]. Metabolomics has also been widely used to measure the changes in metabolites as induced by the administration of supplements and drugs [16,17]. Still, the metabolomic mechanism through which hydrogen can induce bene ts for exercise performance?…”