Találati lista | Tudóstér

001-es BibID:	BIBFORM135200
Első szerző:	Karadsheh, Gyath (biokémia)
Cím:	Thiamine transporter 2 and Janus kinase 2 inhibitor, fedratinib suppresses thermogenic activation of human neck area-derived adipocytes / Karadsheh Gyath, Kovács Emília, Alrifai Rahaf, Seo Mizuki, Győry Ferenc, Csatári-Kovács Renáta, Csősz Éva, Póliska Szilárd, Fésüs László, Arianti Rini, Kristóf Endre
Dátum:	2026
ISSN:	1664-2392
Megjegyzések:	Introduction: Brown adipocytes consume higher amounts of metabolic substrates and regulators, including thiamine, during adrenergic stimulation, supporting heat generation. Our previous findings showed that fedratinib, a potent inhibitor of thiamine transporter (ThTr) 2 and Janus kinase 2 (JAK2), reduced thermogenic activity; however, the underlying molecular mechanisms remain elusive. Methods: Primary human subcutaneous (SC) and deep neck (DN)-derived adipocytes were treated with dibutyryl (db)-cAMP, fedratinib, or the combination of the two compounds after differentiation. Global transcriptomic analysis was performed by bulk RNA-sequencing. Differentially expressed genes were subjected to pathway enrichment analysis. We also utilized publicly available single-cell RNA-sequencing datasets and adiposetissue.org to correlate ThTr2 expression in adipose tissue to clinical parameters of patient cohorts. Amino acid flux was measured by metabolomics. Results and discussion: ThTr2 expression was observed exclusively enriched in the adipocytes cluster within human brown and white adipose tissue. In response to ThTr2 inhibition, the db-cAMP-This is a provisional file, not the final typeset article stimulated upregulation of the canonical thermogenic markers and proton leak respiration, which associates with UCP1-dependent heat generation, was prevented in both adipocyte types. RNA-sequencing found 40 and 41 downregulated genes potentially underlying the metabolic changes in SC and DN-derived adipocytes, respectively, which were involved in various biological pathways, including transcriptional regulation of brown and beige adipocytes differentiation, signaling by interleukins, nicotinamide salvaging, and gene and protein expression by JAK/STAT signaling after interleukin-12 stimulation. The expression of recently identified thermogenesis regulators, such as transglutaminase (TGM) 2 and inhibitor of DNA binding (ID) 1, was also abrogated by ThTr2 inhibition during adrenergic stimulation. Intriguingly, glutamate transporter (GLT) 1 and L-amino acid transporter (LAT) 2 expression was also attenuated by fedratinib, restricting amino acid consumption. Finally, we found that the expression of ThTr2 in human white adipose tissue was inversely correlated with body mass index, waist-hip ratio, leptin secretion, and plasma insulin, glucose, cholesterol, and triacylglycerol levels, supporting the importance of thiamine metabolism in adipocyte and metabolic health.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk fedratinib human adipocytes JAK SLC19A3 thermogenesis thiamine
Megjelenés:	Frontiers in Endocrinology. - 17 (2026), p. 1-15. -
További szerzők:	Kovács Emília Alrifai, Rahaf (1995-) (molekuláris biológus) Seo, Mizuki Győry Ferenc (1964-) (sebész) Csatári-Kovács Renáta (1992-) (klinikai laboratóriumi kutató) Csősz Éva (1977-) (biokémikus, molekuláris biológus) Póliska Szilárd (1978-) (biológus) Fésüs László (1947-) (orvos biokémikus) Arianti, Rini (1991-) (biokémikus) Kristóf Endre (1987-) (általános orvos)
Pályázati támogatás:	FK145866 OTKA FK134605 OTKA PD146202 OTKA TKP2021-NKTA-34 Egyéb
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Saját polcon: