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1.

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
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Intézményi repozitóriumban (DEA) tárolt változat
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2.

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
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Intézményi repozitóriumban (DEA) tárolt változat
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3.

001-es BibID:BIBFORM084780
035-os BibID:(cikkazonosító)987 (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
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4.

001-es BibID:BIBFORM102713
Első szerző:Shaw, Abhirup
Cím:Irisin stimulates the release of CXCL1 via upregulation of NFkB pathway from human neck derived differentiating adipocytes / Shaw Abhirup, B. Tóth Beáta, Győry Ferenc, Fésüs László, Kristóf Endre
Dátum:2022
ISSN:2211-5463
Megjegyzések:Obesity is at present a global epidemic. Brown and beige adipocytes function in utilizing excess fat to produce heat (thermogenesis), thereby counteracting obesity. Recent studies in rodents and humans indicated that these adipocytes also release cytokines, which may play a vital role in maintaining whole body energy homeostasis. Irisin is primarily released by myocytes during exercise and functions as a polypeptide regulator of beige adipocytes. We intended to characterize the effect of irisin on differentiating adipocytes derived from human subcutaneous neck (SC) and deep neck (DN) adipose tissue depots. Preadipocytes were isolated from SC and DN biopsies of the same donor, differentiated to adipocytes in the presence or absence of irisin. Global gene expression analysis was performed on nine independent donors. Irisin could not upregulate characteristic thermogenic genes, but upregulated genes related to several cytokines. Out of them,CXCL1 (the highest upregulated) was found to be released throughout the differentiation period, predominantly by SC and DN differentiated adipocytes. DN tissue biopsies showed a significant release of CXCL1 upon 24 hours irisin treatment. Geneexpression data indicated upregulation of the NFkB pathway upon irisin treatment, which was validated by an increase of p50 and decrease of IkBa protein level, respectively. Continuous blocking of the NFkB pathway by SN50 (cell permeable inhibitorof NFkB nuclear translocation) significantly reduced the release of CXCL1. The released CXCL1 exerted a positive effect on the adhesion capability of endothelial cells. Together, our findings demonstrate that irisin stimulates the release of a novel adipokine, CXCL1, via upregulation of NFkB pathway in human neck area derived differentiating adipocytes, which plays an important role in improving tissue vascularization (Previously published in:Shaw A et al. (2021) Front Cell Dev Biol 9:737872).
Tárgyszavak:Orvostudományok Elméleti orvostudományok idézhető absztrakt
folyóiratcikk
Megjelenés:FEBS Open Bio. - 12 : S1 (2022), p. 208. -
További szerzők:Bartáné Tóth Beáta (1970-) (molekuláris biológus) Győry Ferenc (1964-) (sebész) Fésüs László (1947-) (orvos biokémikus) Kristóf Endre (1987-) (általános orvos)
Pályázati támogatás:FK131424
OTKA
GINOP-2.3.2-15-2016-00006
GINOP
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

5.

001-es BibID:BIBFORM097508
035-os BibID:(cikkazonosító)1078 (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:

6.

001-es BibID:BIBFORM096387
035-os BibID:(cikkazonosító)737872
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
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