The Energetic Cost of Adrenergic Signaling in Primary Human Fibroblasts.
Level 5 - mechanism / opinion, no new human data
In vitro laboratory study in primary human cell cultures (non-clinical mechanism)
PubMed 42465469 · doi:10.64898/2026.07.09.737569
What was done
Primary human fibroblasts were exposed to norepinephrine at concentrations from 0 to 10 µM for up to 10 hours. Oxygen consumption rate (reflecting mitochondrial ATP production) and extracellular acidification rate (reflecting glycolytic ATP production) were measured continuously via extracellular flux analysis. Responses were tested under mitochondrial inhibition (oligomycin or piericidin A), glucose withdrawal, and in cells with genetic defects impairing oxidative phosphorylation.
What was found
Within the first 18 minutes, glycolysis increased by up to 47% while respiration decreased by 2-5%, both normalizing within 1-2 hours at low norepinephrine concentrations. This was followed by a 9-12% increase in oxidative phosphorylation peaking between 2 and 6 hours. Oxidative phosphorylation inhibitors abolished respiration changes while preserving the glycolytic response. Glucose withdrawal dampened the extracellular acidification rate increase and boosted oxidative phosphorylation. Cells with genetic oxidative phosphorylation defects showed a 50% blunted metabolic response to norepinephrine.
Why it matters
This study provides direct, dynamic quantifications of the bioenergetic costs and metabolic flexibility elicited by catecholamine exposure at the single-cell level. It offers a cellular-level mechanism for the energetic demands linked to adrenergic stress responses.
Limits
The study is restricted to in vitro primary fibroblasts and cannot capture whole-body, tissue-level, or neuroendocrine interactions. The abstract omits sample size (number of cell lines or donors), precision estimates, and p-values. The work is a preprint and has not undergone formal peer review.
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- context Stress hormones increase human energy expenditure by 16%.