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001-es BibID:BIBFORM125600
035-os BibID:(Scopus)85209396534 (WoS)001356316700006
Első szerző:Arianti, Rini (biokémikus)
Cím:Upregulation of inhibitor of DNA binding 1 and 3 is important for efficient thermogenic response in human adipocytes / Rini Arianti, Boglárka Ágnes Vinnai, Rahaf Alrifai, Gyath Karadsheh, Yousif Qais Al-Khafaji, Szilárd Póliska, Ferenc Győry, László Fésüs, Endre Kristóf
Dátum:2024
ISSN:2045-2322
Megjegyzések:Brown and beige adipocytes can be activated by β-adrenergic agonist via cAMP-dependent signaling. Performing RNA-sequencing analysis in human cervical area-derived adipocytes, we found that dibutyryl-cAMP, which can mimic in vivo stimulation of browning and thermogenesis, enhanced the expression of browning and batokine genes and upregulated several signaling pathway genes linked to thermogenesis. We observed that the expression of Inhibitor of DNA binding and cell differentiation (ID) 1 and particularly ID3 was strongly induced by the adrenergic stimulation. The degradation of ID1 and ID3 elicited by the ID antagonist AGX51 during thermogenic activation prevented the induction of proton leak respiration that reflects thermogenesis and abrogated cAMP analogue-stimulated upregulation of thermogenic genes and mitochondrial complex I, II, and IV subunits, independently of the proximal cAMP-PKA signaling pathway. The presented data suggests that ID proteins contribute to efficient thermogenic response of adipocytes during adrenergic stimulation.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Adipocytes
Browning
Thermogenesis
Adrenergic stimulation
ID1
ID3
Megjelenés:Scientific Reports. - 14 : 1 (2024), p. 1-13. -
További szerzők:Vinnai Boglárka Ágnes (1996-) (molekuláris biológus) Alrifai, Rahaf (1995-) (molekuláris biológus) Karadsheh, Gyath (1997-) (biokémia) Al-Khafaji, Yousif Qais (2004-) Póliska Szilárd (1978-) (biológus) Győry Ferenc (1964-) (sebész) Fésüs László (1947-) (orvos biokémikus) Kristóf Endre (1987-) (általános orvos)
Pályázati támogatás:FK145866
OTKA
PD146202
OTKA
ÚNKP-23-3-II-DE-156
Egyéb
EKÖP-24-3-II-DE-113
Egyéb
TKP2021-NKTA-34
Egyéb
Internet cím:DOI
Szerző által megadott URL
Intézményi repozitóriumban (DEA) tárolt változat
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2.

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
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3.

001-es BibID:BIBFORM097508
035-os BibID:(WoS)000724148200001 (Scopus)85117925325
Első szerző:Shaw, Abhirup
Cím:BMP7 increases UCP1-dependent and independent thermogenesis with a unique gene expression program in human neck area derived adipocytes / Shaw Abhirup, B. Tóth Beáta, Arianti Rini, Csomós István, Póliska Szilárd, Vámos Attila, Bacsó Zsolt, Győry Ferenc, Fésüs László, Kristóf Endre
Dátum:2021
ISSN:1424-8247
Megjegyzések:White adipocytes contribute to energy storage accumulating lipid droplets, whereas brown and beige adipocytes mainly function in dissipating energy as heat primarily via the action of uncoupling protein 1 (UCP1). Bone morphogenic protein 7 (BMP7) was shown to drive brown adipocyte differentiation in murine interscapular adipose tissue. Here, we performed global RNA-sequencing and functional assays on adipocytes obtained from subcutaneous (SC) and deep-neck (DN) depots of human neck and differentiated with or without BMP7. We found that BMP7 did not influence differentiation but upregulated browning markers, including UCP1 mRNA and protein in SC and DN derived adipocytes. BMP7 also enhanced mitochondrial DNA content, levels of oxidative phosphorylation complex subunits, along with PGC1? and p-CREB upregulation, and fragmentation of mitochondria. Furthermore, both UCP1-dependent proton leak and UCP1-independent, creatine driven substrate cycle coupled thermogenesis were augmented upon BMP7 addition. The gene expression analysis shed light also on possible role of genes unrelated to thermogenesis so far, including ACAN, CRYAB, and ID1, which were amongst the highest upregulated ones by BMP7 treatment in both types of adipocytes. Together, our study shows that BMP7 strongly upregulates thermogenesis in human neck area derived adipocytes, along with genes, which might have a supporting role in energy expenditure.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Pharmaceuticals. - 14 : 11 (2021), p. 1-21. -
További szerzők:Bartáné Tóth Beáta (1970-) (molekuláris biológus) Arianti, Rini (1991-) (biokémikus) Csomós István (1983-) (molekuláris biológus) Póliska Szilárd (1978-) (biológus) Vámos Attila (1991-) (gyógyszer-biotechnológus) Bacsó Zsolt (1963-) (biofizikus) Győry Ferenc (1964-) (sebész) Fésüs László (1947-) (orvos biokémikus) Kristóf Endre (1987-) (általános orvos)
Pályázati támogatás:GINOP-2.3.2-15-2016-00006
GINOP
FK131424
OTKA
K129139
OTKA
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
DOI
Borító:

4.

001-es BibID:BIBFORM096387
Első szerző:Shaw, Abhirup
Cím:Irisin stimulates the release of CXCL1 from differentiating human subcutaneous and deep-neck derived adipocytes via upregulation of NF[kappa]B pathway / Abhirup Shaw, Beáta B. Tóth, Róbert Király, Rini Arianti, István Csomós, Szilárd Póliska, Attila Vámos, Ilma R. Korponay-Szabó, Zsolt Bacso, Ferenc Győry, László Fésüs, Endre Kristóf
Dátum:2021
ISSN:2296-634X
Megjegyzések:Thermogenic brown and beige adipocytes might open up new strategies in combating obesity. Recent studies in rodents and humans have indicated that these adipocytes release cytokines, termed "batokines". Irisin was discovered as a polypeptide regulator of beige adipocytes released by myocytes, primarily during exercise. We performed global RNA sequencing on adipocytes derived from human subcutaneous and deep-neck precursors, which were differentiated in the presence or absence of irisin. Irisin did not exert an effect on the expression of characteristic thermogenic genes, while upregulated genes belonging to various cytokine signaling pathways. Out of the several upregulated cytokines, CXCL1, the highest upregulated, was released throughout the entire differentiation period, and predominantly by differentiated adipocytes. Deep-neck area tissue biopsies also showed a significant release of CXCL1 during 24 hours irisin treatment. Gene expression data indicated upregulation of the NF?B pathway upon irisin treatment, which was validated by an increase of p50 and decrease of I?B? protein level, respectively. Continuous blocking of the NF?B pathway, using a cell permeable inhibitor of NF?B nuclear translocation, significantly reduced CXCL1 release. The released CXCL1 exerted a positive effect on the adhesion of endothelial cells. Together, our findings demonstrate that irisin stimulates the release of a novel adipokine, CXCL1, via upregulation of NF?B pathway in neck area derived adipocytes, which might play an important role in improving tissue vascularization.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Frontiers in Cell and Developmental Biology. - 9 (2021), p. 1-19. -
További szerzők:Bartáné Tóth Beáta (1970-) (molekuláris biológus) Király Róbert (1975-) (biológus) Arianti, Rini (1991-) (biokémikus) Csomós István (1983-) (molekuláris biológus) Póliska Szilárd (1978-) (biológus) Vámos Attila (1991-) (gyógyszer-biotechnológus) Korponay-Szabó Ilma (1959-) (gyermekgyógyász) Bacsó Zsolt (1963-) (biofizikus) Győry Ferenc (1964-) (sebész) Fésüs László (1947-) (orvos biokémikus) Kristóf Endre (1987-) (általános orvos)
Pályázati támogatás:GINOP-2.3.2-15-2016-00006
GINOP
FK131424
OTKA
K129139
OTKA
K120392
OTKA
ÚNKP-20-5-DE-12
Egyéb
BO/00042/18/8
MTA
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:
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