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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
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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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001-es BibID:	BIBFORM067761
Első szerző:	Kristóf Endre (általános orvos)
Cím:	Browning-inducers modify the differentiation of human adipocytes from different anatomical sites and enhance their mitochondrial respiration / Kristóf Endre, Quang-Minh Doan-Xuan, Klusóczki Ágnes, Győry Ferenc, Póliska Szilárd, Bacsó Zsolt, Bai Péter, Fésüs László
Dátum:	2016
Megjegyzések:	Several studies highlighted the strong negative correlation between obesity and active brown adipose tissue amount in adult humans. There are at least two types of thermogenic fat depots, classical brown and beige, which have different origins and tissue distribution. We intended to clarify whether preadipocytes from different anatomical sites are capable of initiating a browning program in parallel with the enhancement of mitochondrial respiration in response to browning-inducers. Preadipocytes obtained from herniotomy (abdominal subcutaneous) or thyroid surgery ("deep neck" and cervical subcutaneous) and a human preadipocyte cell line (SGBS) were differentiated into white, brown (by BMP7 treatment) or beige (by irisin and clozapine administration or by a previously described cocktail) adipocytes. To assess browning, gene expression measurements and laser-scanning cytometry based morphology analysis were performed. Oxygen consumption was measured using an XF96 oxymeter. Differentiating adipocytes treated with browning-inducers had smaller lipid droplets, more mitochondrial DNA, higher mitochondrial respiration and contained more Ucp1 protein than white adipocytes. Browning adipocytes utilize more fatty acids by beta-oxidation and increase their respiration by activating a futile cycle of creatine metabolism. Next, we intend to identify molecular markers to characterize those preadipocytes that are capable to implement an effective browning program.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idézhető absztrakt
Megjelenés:	Journal of World Mitochondria Society. - 2 : 2 (2016), p. 23. -
További szerzők:	Doan-Xuan, Quang-Minh (1986-) (biofizikus) Klusóczki Ágnes (1991-) (biotechnológus) Győry Ferenc (1969-) (kardiológus) Póliska Szilárd (1978-) (biológus) Bacsó Zsolt (1963-) (biofizikus) Bai Péter (1976-) (biokémikus) Fésüs László (1947-) (orvos biokémikus)
Pályázati támogatás:	NK 105046 OTKA GINOP-2.3.2-15-2016-00006 GINOP
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	BIBFORM066378
Első szerző:	Kristóf Endre (általános orvos)
Cím:	Differentiating human beige adipocytes secrete cytokines ("batokines") / Endre Kristóf, Ágnes Klusóczki, Zsolt Combi, Roland Veress, Ferenc Győry, Szilárd Póliska, Zsolt Bacsó, László Fésüs
Dátum:	2016
Megjegyzések:	Several studies highlighted the strong negative correlation between obesity and metabolically active brown adipose tissue amount in adult humans. There are at least two types of thermogenic fat depots, classical brown and beige, which have different origins and tissue distribution. Beige adipocytes contribute to the regulation of systemic metabolic homeostasis not exclusively by thermogenesis and mitochondrial uncoupling. In the present study, we investigated the secretion of "batokines" by primary human brown and beige adipocytes and by human adipose tissue samples. Adipose-derived mesenchymal stem cells obtained from herniotomy (abdominal subcutaneous) or thyroid surgery ("deep neck" and cervical subcutaneous) and a human preadipocyte cell line (SGBS) were differentiated into white, brown (by BMP7 treatment) or beige (by irisin administration or by a previously described cocktail) adipocytes. Cytokine gene expression in browning adipocytes was determined by RNA sequencing. Conditioned differentiation media were collected during the replacement of the adipogenic cocktails and secreted IL-6, IL-8, TNF?, MCP-1 and IL1-? were measured by ELISA. IL-6, MCP-1 and IL-8 secretion was significantly higher by beige compared to white adipocytes. In contrast to BMP7 administration (when classical brown adipocyte differentiation occurs), irisin treatment (which induces beige adipocyte differentiation) resulted in an increased total IL-6, MCP-1 and IL-8 production. Media collected daily or after three day periods contained the same amount of IL-6 depending only on the phase of differentiation. This suggests that adipocytes adjusted their production of the cytokine to reach an optimal level in the medium. In the heterogeneous population of differentiating adipocytes, IL-6 containing vesicles could be visualized mostly in beige cells by Laser-scanning cytometry. In the future we intend to explore the functional significance of the produced "batokines".
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idézhető absztrakt
Megjelenés:	Biokémia. - 40 : 3 (2016), p. 37. -
További szerzők:	Klusóczki Ágnes (1991-) (biotechnológus) Combi Zsolt Veress Roland (1992-) (molekuláris biológus) Győry Ferenc (1969-) (kardiológus) Póliska Szilárd (1978-) (biológus) Bacsó Zsolt (1963-) (biofizikus) Fésüs László (1947-) (orvos biokémikus)
Pályázati támogatás:	TÁMOP-4.2.2.A-11/1/KONV-2012-0023 TÁMOP TÁMOP-4.2.2.A-11/1/KONV-2012-0025 TÁMOP TRANSCOM IAPP 251506 FP7 MTA-DE MTA Apoptózis és Genomika Kutatócsoport NK105046 OTKA GINOP-2.3.2-15-2016-00006 GINOP
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat
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