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1.
001-es BibID:
BIBFORM111915
035-os BibID:
(scopus)85161297715
Első szerző:
Arianti, Rini (biokémikus)
Cím:
Availability of abundant thiamine determines efficiency of thermogenic activation in human neck area derived adipocytes / Arianti Rini, Vinnai Boglárka Ágnes, Győry Ferenc, Guba Andrea, Csősz Éva, Kristóf Endre, Fésüs László
Dátum:
2023
ISSN:
0955-2863
Megjegyzések:
Brown/beige adipocytes express uncoupling protein-1 (UCP1) that enables them to dissipate energy as heat. Systematic activation of this process can alleviate obesity. Human brown adipose tissues are interspersed in distinct anatomical regions including deep neck. We found that UCP1 enriched adipocytes differentiated from precursors of this depot highly expressed ThTr2 transporter of thiamine and consumed thiamine during thermogenic activation of these adipocytes by cAMP which mimics adrenergic stimulation. Inhibition of ThTr2 led to lower thiamine consumption with decreased proton leak respiration reflecting reduced uncoupling. In the absence of thiamine, cAMP-induced uncoupling was diminished but restored by thiamine addition reaching the highest levels at thiamine concentrations larger than present in human blood plasma. Thiamine is converted to thiamine pyrophosphate (TPP) in cells; the addition of TPP to permeabilized adipocytes increased uncoupling fueled by TPP-dependent pyruvate dehydrogenase. ThTr2 inhibition also hampered cAMP-dependent induction of UCP1, PGC1a, and other browning marker genes, and thermogenic induction of these genes was potentiated by thiamine in a concentration dependent manner. Our study reveals the importance of amply supplied thiamine during thermogenic activation in human adipocytes which provides TPP for TPP-dependent enzymes not fully saturated with this cofactor and by potentiating the induction of thermogenic genes.
Tárgyszavak:
Orvostudományok
Elméleti orvostudományok
idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
human adipocytes
thiamine
thiamine transporter
pyruvate dehydrogenase
thermogenesis
UCP1 expression
Megjelenés:
Journal Of Nutritional Biochemistry. - 119 (2023), p. 1-13. -
További szerzők:
Vinnai Boglárka Ágnes (1996-) (molekuláris biológus)
Győry Ferenc (1964-) (sebész)
Guba Andrea (1975-) (Okleveles vegyész)
Csősz Éva (1977-) (biokémikus, molekuláris biológus)
Kristóf Endre (1987-) (általános orvos)
Fésüs László (1947-) (orvos biokémikus)
Pályázati támogatás:
GINOP-2.3.2-15-2016-00006
GINOP
FK131424
OTKA
K129139
OTKA
ÚNKP-22-3-I
Egyéb
Internet cím:
Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Saját polcon:
2.
001-es BibID:
BIBFORM096051
035-os BibID:
(WoS)000676122000001 (Scopus)85111301797
Első szerző:
Arianti, Rini (biokémikus)
Cím:
ASC-1 transporter-dependent amino acid uptake is required for the efficient thermogenic response of human adipocytes to adrenergic stimulation / Rini Arianti, Boglarka Agnes Vinnai, Beata B. Toth, Abhirup Shaw, Eva Csosz, Attila Vamos, Ferenc Gyory, Pamela Fischer-Posovszky, Martin Wabitsch, Endre Kristof, Laszlo Fesus
Dátum:
2021
ISSN:
0014-5793
Megjegyzések:
Brown and beige adipocytes dissipate energy by uncoupling protein 1 (UCP1)-dependent and UCP1-independent thermogenesis, which may be utilized to develop treatments against obesity. We have found that mRNA and protein expression of the alanine/serine/cysteine transporter-1 (ASC-1) was induced during adipocyte differentiation of human brown-prone deep neck and beige-competent subcutaneous neck progenitors, and SGBS preadipocytes. cAMP stimulation of differentiated adipocytes led to elevated uptake of serine, cysteine, and glycine, in parallel with increased oxygen consumption, augmented UCP1-dependent proton leak, increased creatine-driven substrate cycle-coupled respiration, and upregulation of thermogenesis marker genes and several respiratory complex subunits; these outcomes were impeded in the presence of the specific ASC-1 inhibitor, BMS-466442. Our data suggest that ASC-1-dependent consumption of serine, cysteine, and glycine is required for efficient thermogenic stimulation of human adipocytes.
Tárgyszavak:
Orvostudományok
Elméleti orvostudományok
idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
adipocytes
ASC-1 inhibition
gene expression
obesity
proton leak respiration
thermogenesis
uncoupling protein
Megjelenés:
Febs Letters. - 595 : 16 (2021), p. 2085-2098. -
További szerzők:
Vinnai Boglárka Ágnes (1996-) (molekuláris biológus)
Bartáné Tóth Beáta (1970-) (molekuláris biológus)
Shaw, Abhirup (1992-)
Csősz Éva (1977-) (biokémikus, molekuláris biológus)
Vámos Attila (1991-) (gyógyszer-biotechnológus)
Győry Ferenc (1964-) (sebész)
Fischer-Posovszky Pamela
Wabitsch, Martin
Kristóf Endre (1987-) (általános orvos)
Fésüs László (1947-) (orvos biokémikus)
Pályázati támogatás:
GINOP-2.3.2-15-2016-00006
GINOP
EFOP-3.6.3-VEKOP-16-2017-00009
EFOP
FK131424
OTKA
K129139
OTKA
ÚNKP-20-5-DE-12
Egyéb
ÚNKP-20-2-I-DE-187
Egyéb
Internet cím:
Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Saját polcon:
3.
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:
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