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1.
001-es BibID:
BIBFORM136094
035-os BibID:
(scopus)105031584671 (wos)001703263700001
Első szerző:
Alrifai, Rahaf (molekuláris biológus)
Cím:
Transferrin receptor 1-mediated iron uptake supports thermogenic activation in human cervical-derived adipocytes / Alrifai Rahaf, Seo Mizuki, Karadsheh Gyath, Mahendra Fachrur Rizal, Demény Máté Á., Győry Ferenc, Mótyán János András, Fésüs László, Kristóf Endre, Arianti Rini
Dátum:
2026
ISSN:
0014-5793
Megjegyzések:
Adrenergic-driven thermogenic activation of brown adipose tissue requires high amounts of nutrients including iron to support mitochondrial biogenesis. This is governed by rapid gene expression changes in ex vivo differentiated human cervical-derived brown adipocytes. Transferrin receptor 1 (TFRC) is upregulated in response to dibutyryl-cAMP. We aim to investigate the mechanism of facilitated iron uptake when thermogenesis is activated. Pharmacological inhibition and siRNA-mediated knock-down of TFRC during stimulation decrease intracellular iron content and prevent elevation of oxygen consumption and induction of thermogenic markers. Deferoxamine-mediated iron chelation also shows comparable effects. Contrarily, the expression of ferroportin exporter is suppressed during activation; however, its inhibition does not increase thermogenesis. Brown adipocytes constitutively express and secrete high amounts of transferrin, while melanotransferrin expression and release are upregulated only in activated adipocytes. In silico analysis suggests that melanotransferrin interacts with the helical domain of TFRC. Our findings support that iron is critical in stimulating adipocyte thermogenesis.
Tárgyszavak:
Orvostudományok
Elméleti orvostudományok
idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:
Febs Letters. - [Epub ahead of print] (2026). -
További szerzők:
Seo, Mizuki
Karadsheh, Gyath (1997-) (biokémia)
Mahendra, Fachrur Rizal
Demény Máté Ágoston (1976-) (molekuláris biológus)
Győry Ferenc (1964-) (sebész)
Mótyán János András (1981-) (biokémikus, molekuláris biológus)
Fésüs László (1947-) (orvos biokémikus)
Kristóf Endre (1987-) (általános orvos)
Arianti, Rini (1991-) (biokémikus)
Pályázati támogatás:
FK145866
OTKA
PD146202
OTKA
BO/00110/23/5
MTA
Gedeon Richter PhD Scholarship
Egyéb
Stipendium Hungaricum Scholarship
Egyéb
Internet cím:
Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Saját polcon:
2.
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
Borító:
Saját polcon:
3.
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:
4.
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:
5.
001-es BibID:
BIBFORM079713
035-os BibID:
(WoS)000486972404107
Első szerző:
Arianti, Rini (biokémikus)
Cím:
Identification of unique molecular signature ofbrowning in human primary adipocytes fromdeep and subcutaneous neck fat / Arianti Rini, Shaw Abhirup, Vámos Attila, Bartáné Tóth Beáta, Győry Ferenc, Póliska Szilárd, Kristóf Endre Károly, Fésüs László
Dátum:
2019
ISSN:
2211-5463
Megjegyzések:
There are two types of thermogenic adipocytes, classical brown and beige (BAT) which are UCP1-positive dissipating energy as heat. BAT markers have been well studied in rodents but detailed molecular studies are still lacking in humans where BAT is interspersed at several sites and may serve as a target of anti-obesity therapies. Our study aims to identify the unique signature of browning in human primary adipocytes from the different anatomical location by analyzing global gene expression patterns. Preadipocytes were obtained from subcutaneous (SC) and deep neck (DN) and differentiated to white and brown adipocytes. We analyzed differential gene expressions by total RNA sequencing, molecular pathways by KEGG Mapper, genetic constraint by ExAC and verified several genes of interest associated with adipocytes browning. We identified 37 genes which are closely clustered to UCP1. Out of those 13 genes have been already described to play a role in thermogenesis (CIDEA, CKMT1A/B), while the roles of the others are still unclear (ANO5, FAM151a). Several pathways were represented, such as retinoic acid biosynthesis which was upregulated (CPT1, CYP261B), while extracellular matrix organization pathways were among the downregulated ones (COL, ITGF). Mitochondrial creatine kinases, CKMT1a/b, are reported to play role in UCP1-independent thermogenesis; UCP1 and CKMT1a were expressed higher in DN, as compared to SC adipocytes and this was verified by RT-qPCR. Several transporters were expressed higher in DN, such as transporter of amino acids (SLC7A10), glutamate (SLC25A18) and pyruvate (SLC16A7). Our data proves that progenitors from DN fat can be differentiated to browning adipocytes at a greater extent than SC ones. We have started to investigate revealed molecular elements not linked yet to browning by deleting, inhibiting or overexpressing them.
Tárgyszavak:
Orvostudományok
Elméleti orvostudományok
poszter
folyóiratcikk
Megjelenés:
FEBS Open Bio. - 9 : S1 (2019), p. 289-290. -
További szerzők:
Shaw, Abhirup (1992-)
Vámos Attila (1991-) (gyógyszer-biotechnológus)
Bartáné Tóth Beáta (1970-) (molekuláris biológus)
Győry Ferenc (1969-) (kardiológus)
Póliska Szilárd (1978-) (biológus)
Kristóf Endre (1987-) (általános orvos)
Fésüs László (1947-) (orvos biokémikus)
Pályázati támogatás:
GINOP-2.3.2-15-2016-00006
GINOP
Internet cím:
Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Saját polcon:
6.
001-es BibID:
BIBFORM084780
035-os BibID:
(WOS)000535559500198 (Scopus)85083871362
Első szerző:
Bartáné Tóth Beáta (molekuláris biológus)
Cím:
FTO intronic SNP strongly influences human neck adipocyte browning determined by tissue and PPARγ specific regulation : a transcriptome analysis / Bartáné Tóth Beáta, Arianti Rini, Shaw Abhirup, Vámos Attila, Veréb Zoltán, Póliska Szilárd, Győry Ferenc, Bacsó Zsolt, Fésüs László, Kristóf Endre Károly
Dátum:
2020
ISSN:
2073-4409
Megjegyzések:
Brown adipocytes, abundant in deep-neck (DN) area in humans, are thermogenic with anti-obesity potential. FTO pro-obesity rs1421085 T-to-C SNP shifts differentiation program towards white adipocytes in subcutaneous fat. Human adipose-derived stromal cells were obtained from subcutaneous neck (SC) and DN fat of 9 donors, of which 3-3 carried risk-free (T/T), heterozygous or obesity-risk (C/C) FTO genotypes. They were differentiated to white and brown (long-term PPAR? stimulation) adipocytes, then global RNA sequencing was performed and differentially expressed genes (DEGs) were compared. DN and SC progenitors had similar adipocyte differentiation potential but differed in DEGs. DN adipocytes displayed higher browning features according to ProFAT or BATLAS scores and characteristic DEG patterns revealing associated pathways which were highly expressed (thermogenesis, interferon, cytokine, retinoic acid, with UCP1 and BMP4 as prominent network stabilizers) or downregulated (particularly extracellular matrix remodelling) compared to SC ones. Part of DEGs in either DN or SC browning was PPAR?-dependent. Presence of the FTO obesity-risk allele suppressed the expression of mitochondrial and thermogenesis genes with a striking resemblance between affected pathways and those appearing in ProFAT and BATLAS, underlining the importance of metabolic and mitochondrial pathways in thermogenesis. Among overlapping regulatory influences which determine browning and thermogenic potential of neck adipocytes, FTO genetic background has a so far not recognized prominence.
Tárgyszavak:
Orvostudományok
Elméleti orvostudományok
idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
adipocyte browning
differential gene expression patterns
deep-neck
PPARg
FTO obesity-risk allele
Megjelenés:
Cells. - 9 : 4 (2020), p. 1-25. -
További szerzők:
Arianti, Rini (1991-) (biokémikus)
Shaw, Abhirup (1992-)
Vámos Attila (1991-) (gyógyszer-biotechnológus)
Veréb Zoltán (1980-) (immunológus, mikrobiológus, molekuláris biológus)
Póliska Szilárd (1978-) (biológus)
Győry Ferenc (1969-) (kardiológus)
Bacsó Zsolt (1963-) (biofizikus)
Fésüs László (1947-) (orvos biokémikus)
Kristóf Endre (1987-) (általános orvos)
Pályázati támogatás:
GINOP-2.3.2-15-2016-00006
GINOP
FIKP_20428-3_2018_FELITSTRAT
FIKP
FK131424
OTKA
K129139
OTKA
EFOP-3.6.3-VEKOP-16-2017-00009
EFOP
ÚNKP-19-4-DE-42
Egyéb
Internet cím:
Intézményi repozitóriumban (DEA) tárolt változat
DOI
Borító:
Saját polcon:
7.
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:
8.
001-es BibID:
BIBFORM131954
Első szerző:
Kristóf Endre (általános orvos)
Cím:
LAT1-mediated amino acid transport supports thermogenesis of human brown adipocytes / Kristóf Endre, Arianti Rini, Enyedi Nóra, Vinnai Boglárka Ágnes, Alrifai Rahaf, Karadsheh Gyath, Póliska Szilárd, Csősz Éva, Fésüs László
Dátum:
2025
ISSN:
2211-5463
Megjegyzések:
Thermogenically active adipocytes utilize high amounts of metabolic substrates, such as glucose, fatty acids, and amino acids (AAs), which provide sufficient energy for heat generation via UCP1-mediated proton leak in the inner membrane of mitochondria. However, the mechanism of how brown adipocytes can uptake distinct types of AAs remains unclear. Our preliminary data showed that the consumption of branched-chain and other AAs as well as the expression of L-amino acid transporter (LAT) 1 (encoded by SLC7A5) and its heterodimer protein 4F2hc (encoded by SLC3A2) was upregulated during adrenergic stimulation [Previously published in: Arianti R et al. (2024) Sci Rep 14, 28272]. Therefore, we aimed to investigate the role of LAT1 in the thermogenesis of human brown adipocytes. Stromal vascular fraction was isolated from cervical adipose tissue biopsies and differentiated into brown adipocytes for 14?days. The expression of LAT1 was silenced by siRNA-mediated interference and then dibutyryl-cAMP was administered to mimic in vivo thermogenesis. We found that LAT1 deficiency in adrenergic stimulated matured adipocytes inhibited AA influx and led to reduced proton leak respiration which is associated with UCP1-dependent heat generation. Dibutyryl-cAMP-stimulated elevation of Etomoxir-resistant respiration, which correlates with glucose and amino acid utilization, was also abrogated in LAT1 knock-down adipocytes. LAT1 silencing also resulted in decreased expression of thermogenic markers, such as UCP1 and PPARGC1a during adrenergic stimulation, as well as genes which were involved in various biological pathways, such as the TGF-?, MAPK, or PI3K-Akt signaling. Our data suggest that LAT1 regulates human brown adipocyte thermogenesis by mediating the uptake of several AAs to support the high metabolic activity and by controlling the transcriptional program of thermogenesis-related genes.
Tárgyszavak:
Orvostudományok
Elméleti orvostudományok
poszter
folyóiratcikk
Megjelenés:
FEBS Open Bio. - 15 : Suppl. 2 (2025), p. 70-71. -
További szerzők:
Arianti, Rini (1991-) (biokémikus)
Enyedi Nóra
Vinnai Boglárka Ágnes (1996-) (molekuláris biológus)
Alrifai, Rahaf (1995-) (molekuláris biológus)
Karadsheh, Gyath (1997-) (biokémia)
Póliska Szilárd (1978-) (biológus)
Csősz Éva (1977-) (biokémikus, molekuláris biológus)
Fésüs László (1947-) (orvos biokémikus)
Internet cím:
Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Saját polcon:
9.
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:
Saját polcon:
10.
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:
Saját polcon:
11.
001-es BibID:
BIBFORM116662
035-os BibID:
(Scopus)85171172955 (WoS)001169465700001
Első szerző:
Vámos Attila (gyógyszer-biotechnológus)
Cím:
Corrigendum : Human abdominal subcutaneous-derived active beige adipocytes carrying FTO rs1421085 obesity-risk alleles exert lower thermogenic capacity / Vámos Attila, Arianti Rini, Vinnai Boglárka Ágnes, Alrifai Rahaf, Shaw Abhirup, Póliska Szilárd, Guba Andrea, Csősz Éva, Csomós István, Mocsár Gábor, Lányi Cecilia, Balajthy Zoltán, Fésüs László, Kristóf Endre
Dátum:
2023
ISSN:
2296-634X
Megjegyzések:
In the published article, there was an error. In the published article, the Reference "Bjune et al., 2005" was cited with an incorrect year of publication. The correct year of publication is 2019. In the published article "Bjune, J. I., Haugen, C., Gudbrandsen, O., Nordb?, O. P., Nielsen, H. J., V?age, V., et al. (2019). IRX5 regulates adipocyte amyloid precursor protein and mitochondrial respiration in obesity. Int J Obes (Lond)., 43(11), 2151?2162. https://doi.org/10.1038/s41366-018-0275-y" was not referenced in the article. The reference has now been inserted into the article. A correction has been made to the Introduction. This sentence previously stated: "In addition, IRX5 silencing increased the mitochondrial respiration in isolated mouse adipocytes (Bjune et al., 2005)." The corrected sentence appears below: "In addition, IRX5 silencing increased the mitochondrial respiration in isolated mouse adipocytes (Bjune et al., 2019)." The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated. Copyright ? 2023 Vámos, Arianti, Vinnai, Alrifai, Shaw, Póliska, Guba, Csősz, Csomós, Mocsár, Lányi, Balajthy, Fésüs and Kristóf.
Tárgyszavak:
Orvostudományok
Elméleti orvostudományok
hozzászólás
folyóiratcikk
adipocytes
beige
FTO rs1421085
obesity
SLC7A10
thermogenesis
UCP 1
Megjelenés:
Frontiers in Cell and Developmental Biology. - 11 (2023), p. 1-2. -
További szerzők:
Arianti, Rini (1991-) (biokémikus)
Vinnai Boglárka Ágnes (1996-) (molekuláris biológus)
Alrifai, Rahaf (1995-) (molekuláris biológus)
Shaw, Abhirup (1992-)
Póliska Szilárd (1978-) (biológus)
Guba Andrea (1975-) (Okleveles vegyész)
Csősz Éva (1977-) (biokémikus, molekuláris biológus)
Csomós István (1983-) (molekuláris biológus)
Mocsár Gábor (1981-) (biofizikus)
Lányi Cecília
Balajthy Zoltán (1957-) (biokémikus, sejtbiológus)
Fésüs László (1947-) (orvos biokémikus)
Kristóf Endre (1987-) (általános orvos)
Internet cím:
Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Saját polcon:
12.
001-es BibID:
BIBFORM112108
035-os BibID:
(Scopus)85164495947 (WoS)001023372700001
Első szerző:
Vámos Attila (gyógyszer-biotechnológus)
Cím:
Human Abdominal Subcutaneous-Derived Active Beige Adipocytes Carrying FTO rs1421085 Obesity-Risk Alleles Exert Lower Thermogenic Capacity / Vámos Attila, Arianti Rini, Vinnai Boglárka Ágnes, Alrifai Rahaf, Shaw Abhirup, Póliska Szilárd, Guba Andrea, Csősz Éva, Csomós István, Mocsár Gábor, Lányi Cecília, Balajthy Zoltán, Fésüs László, Kristóf Endre
Dátum:
2023
ISSN:
2296-634X
Megjegyzések:
White adipocytes store lipids, have a large lipid droplet and few mitochondria. Brown and beige adipocytes, which produce heat, are characterized by high expression of uncoupling protein (UCP) 1, multilocular lipid droplets, and large amounts of mitochondria. The rs1421085 T-to-C single-nucleotide polymorphism (SNP) of the human FTO gene interrupts a conserved motif for ARID5B repressor, resulting in adipocyte type shift from beige to white. We obtained abdominal subcutaneous adipose tissue from donors carrying FTO rs1421085 TT (risk-free) or CC (obesity-risk) genotypes, isolated and differentiated their preadipocytes into beige adipocytes (driven by the PPAR? agonist rosiglitazone for 14 days), and activated them with dibutyryl-cAMP for 4 hours. Then, either the same culture conditions were applied for additional 14 days (active beige adipocytes) or it was replaced by a white differentiation medium (inactive beige adipocytes). White adipocytes were differentiated by their medium for 28 days. RNA-sequencing was performed to investigate the gene expression pattern of adipocytes carrying different FTO alleles and found that active beige adipocytes had higher brown adipocyte content and browning capacity compared to white or inactive beige ones when the cells were obtained from risk-free TT but not from obesity-risk CC genotype carriers. Active beige adipocytes carrying FTO CC had lower thermogenic gene (e.g., UCP1, PM20D1, CIDEA) expression and thermogenesis measured by proton leak respiration as compared to TT carriers. In addition, active beige adipocytes with CC alleles exerted lower expression of ASC-1 neutral amino acid transporter (encoded by SLC7A10) and less consumption of Ala, Ser, Cys, and Gly as compared to risk-free carriers. We did not observe any influence of the FTO rs1421085 SNP on white and inactive beige adipocytes highlighting its exclusive and critical effect when adipocytes were activated for thermogenesis.
Tárgyszavak:
Orvostudományok
Elméleti orvostudományok
idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
adipocytes
beige
obesity
FTO rs1421085
thermogenesis
UCP1
SLC7A10
Megjelenés:
Frontiers in Cell and Developmental Biology. - 11 (2023), p. 1-18. -
További szerzők:
Arianti, Rini (1991-) (biokémikus)
Vinnai Boglárka Ágnes (1996-) (molekuláris biológus)
Alrifai, Rahaf (1995-) (molekuláris biológus)
Shaw, Abhirup (1992-)
Póliska Szilárd (1978-) (biológus)
Guba Andrea (1975-) (Okleveles vegyész)
Csősz Éva (1977-) (biokémikus, molekuláris biológus)
Csomós István (1983-) (molekuláris biológus)
Mocsár Gábor (1981-) (biofizikus)
Lányi Cecília
Balajthy Zoltán (1957-) (biokémikus, sejtbiológus)
Fésüs László (1947-) (orvos biokémikus)
Kristóf Endre (1987-) (általános orvos)
Pályázati támogatás:
FK131424
OTKA
K129139
OTKA
ÚNKP-22-3-I-DE-30
Egyéb
ÚNKP-22-3-II-DE-25
Egyéb
Internet cím:
Szerző által megadott URL
Intézményi repozitóriumban (DEA) tárolt változat
DOI
Borító:
Saját polcon:
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