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Irisin may be involved in exendin-4 mitochondrial action in human adipocytes

Year: 2026
Type: article
Abstract: Introduction: Disturbed mitochondrial activity in adipocytes has been proposed as one of the mechanisms involved in metabolic dysfunction in obesity. Glucagon-like peptide receptor agonists (GLP-1RAs) are used to normalize glucose level and reduce body weight. GLP-1 activates intracellular pathways similar to those of irisin, a peptide that modulates metabolism by stimulating the 'browning' of adipocytes. The aim of the study was to investigate the mechanisms of action of the GLP-1RA exendin-4 at the mRNA, protein, and mitochondrial levels in human adipocytes. Material and methods: to mature adipocytes and then stimulated with exendin-4 at 100 nM for 24 h. Expression levels of mRNA and proteins (irisin, adiponectin, visfatin/NAMPT) were measured. Oxygen consumption rates and intracellular ATP content were determined. Results: Exendin-4 enhanced the secretion of irisin and visfatin by adipocytes. Upregulated expression of FNDC5, NAMPT, and UCP2 genes was accompanied by modest changes in mitochondrial activity in exendin-4-treated adipocytes. Exendin-4 exerted a similar effect on mitochondrial oxygen consumption rates as irisin, including increased maximum mitochondrial respiration and reserve capacity with unchanged intracellular ATP. Conclusions: Increasing energy expenditure by exendin-4 may be associated with upregulation of irisin in human adipocytes. Clinical studies are necessary to confirm the hypothesis that nutrients, by stimulating the secretion of GLP-1, may influence the expression of irisin and thus modulate the mitochondrial metabolism of adipocytes.
Language: English
Subfield: Physiology
Field: Medicine
Open Access status: gold
Estimated APC paid: $1,078
OpenAlex ID: W7148627660
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