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1.

001-es BibID:BIBFORM096051
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
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K129139
OTKA
ÚNKP-20-5-DE-12
Egyéb
ÚNKP-20-2-I-DE-187
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Intézményi repozitóriumban (DEA) tárolt változat
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2.

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
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Intézményi repozitóriumban (DEA) tárolt változat
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3.

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
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4.

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
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Intézményi repozitóriumban (DEA) tárolt változat
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5.

001-es BibID:BIBFORM095719
035-os BibID:(WoS)000668898600016
Első szerző:Shaw, Abhirup
Cím:Mitophagy is downregulated upon thermogenic stimulus in human beige adipocytes / Shaw Abhirup, Szatmári-Tóth Mária, Csomós István, Mocsár Gábor, Balajthy Zoltán, Győry Ferenc, Kristóf Endre Károly, Fésüs László
Dátum:2021
ISSN:2211-5463
Megjegyzések:Adipocytes are classi?ed into white, brown and beige. Brown and beige adipocytes are important targets to combat obesity, as they are capable to dissipate energy in the form of heat, while the white adipocytes are primarily for energy storage. UCP1, an inner mitochondrial membrane protein mediates thermogenesis by uncoupling the mitochondrial respiratory chain from ATP synthesis. Hence, mitochondria are important for the thermogenic and metabolic functions of adipocytes. UCP1+ mitochondria in human adipocytes are mostly fragmented (Pisani et al, 2017). Mitophagy plays a vital role in beige to white adipocyte transition in mouse (Altshuler-Keylin et al, 2016). We intend to characterize the role of mitophagy in the thermogenic activation of primary human abdominal subcutaneous adipocytes and SGBS cells. Isolated preadipocytes were differentiated into white and browning adipocytes, which were treated with dibutyryl-cAMP (6, 10 and 14 hours). Genes related to parkin-dependent and independent mitophagy were downregulated upon thermogenic stimulus; the parkin dependent ones being the most downregulated. The lipidated form of LC3, LC3-II is recruited on the outer membrane of the autophagosome which indicates ongoing autophagy. TOM20 is an outer mitochondrial membrane protein and marks the mitochondria. LC3 and TOM20 immunostaining were performed, followed by quanti?cation of LC3 punctae,which was high in untreated control adipocytes but decreased signi?cantly upon thermogenic stimulus, suggesting repressed autophagy/mitophagy. Colocalization of TOM20 and LC3 can indicate mitophagy. Decreased colocalization was observed upon thermogenic stimulus, which further proved repressed mitophagy.TOM20 quanti?cation showed increased number of fragmented mitochondria upon thermogenic stimulus suggesting prompt inhibition of mitophagy, thereby protecting many fragmented mitochondria from degradation and boosting thermogenesis.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idézhető absztrakt
folyóiratcikk
Megjelenés:FEBS Open Bio. - 11 : S1 (2021), p. 9. -
További szerzők:Szatmári-Tóth Mária (1987-) (molekuláris biológus) Csomós István (1983-) (molekuláris biológus) Mocsár Gábor (1981-) (biofizikus) Balajthy Zoltán (1957-) (biokémikus, sejtbiológus) Győry Ferenc (1964-) (sebész) 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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6.

001-es BibID:BIBFORM087859
035-os BibID:(cikkazonosító)6640 (scopus)85090621567 (wos)000580228400001
Első szerző:Szatmári-Tóth Mária (molekuláris biológus)
Cím:Thermogenic Activation Downregulates High Mitophagy Rate in Human Masked and Mature Beige Adipocytes / Mária Szatmári-Tóth, Abhirup Shaw, István Csomós, Gábor Mocsár, Pamela Fischer-Posovszky, Martin Wabitsch, Zoltán Balajthy, Cecília Lányi, Ferenc Győry, Endre Kristóf, László Fésüs
Dátum:2020
ISSN:1661-6596 1422-0067
Megjegyzések:Thermogenic brown and beige adipocytes oxidize metabolic substrates producing heat, mainly by the mitochondrial uncoupling protein UCP1, and can thus counteract obesity. Masked beige adipocytes possess white adipocyte-like morphology, but can be made thermogenic by adrenergic stimuli. We investigated the regulation of mitophagy upon thermogenic activation of human masked and mature beige adipocytes. Human primary abdominal subcutaneous adipose-derived stromal cells (hASCs) and SGBS preadipocytes were differentiated to white and beige adipocytes, then their cAMP-induced thermogenic potential was assessed by detecting increased expressions of UCP1, mitochondrial DNA content and respiratory chain complex subunits. cAMP increased the thermogenic potential of white adipocytes similarly to beige ones, indicating the presence of a masked beige population. In unstimulated conditions, a high autophagic flux and mitophagy rates (demonstrated by LC3 punctae and TOM20 co-immunostaining) were observed in white adipocytes, while these were lower in beige adipocytes. Silencing and gene expression experiments showed that the ongoing mitophagy was Parkin-independent. cAMP treatment led to the downregulation of mitophagy through PKA in both types of adipocytes, resulting in more fragmented mitochondria and increased UCP1 levels. Our data indicates that mitophagy is repressed upon encountering a short-term adrenergic stimulus, as a fast regulatory mechanism to provide high mitochondrial content for thermogenesis.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:International Journal of Molecular Sciences. - 21 : 18 (2020), p. 1-21. -
További szerzők:Shaw, Abhirup (1992-) Csomós István (1983-) (molekuláris biológus) Mocsár Gábor (1981-) (biofizikus) Fischer-Posovszky Pamela Wabitsch, Martin Balajthy Zoltán (1957-) (biokémikus, sejtbiológus) Lányi Cecília Győry Ferenc (1964-) (sebész) 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-20-5-DE-12
Egyéb
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
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