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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
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2.

001-es BibID:BIBFORM125264
035-os BibID:(Scopus)85208647721 (WoS)001352685100001
Első szerző:Arianti, Rini (biokémikus)
Cím:Editorial : Novel regulatory mechanisms behind thermogenesis of brown and beige adipocytes, volume II / Arianti Rini, Shaw Abhirup, Kristóf Endre, Cereijo Rubén
Dátum:2024
ISSN:1664-2392
Tárgyszavak:Orvostudományok Elméleti orvostudományok szerkesztői levél
folyóiratcikk
obesity
brown adipocytes
beige adipocytes
UCP 1
thermogenesis
beigeing
browning
Megjelenés:Frontiers in Endocrinology. - 15 (2024), p. 1-3. -
További szerzők:Shaw, Abhirup (1992-) Kristóf Endre (1987-) (általános orvos) Cereijo, Rubén
Pályázati támogatás:PD146202
OTKA
FK145866
OTKA
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
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3.

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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4.

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
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5.

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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6.

001-es BibID:BIBFORM095790
Első szerző:Arianti, Rini (biokémikus)
Cím:Influence of Single Nucleotide Polymorphism of ENPP1 and ADIPOQ on Insulin Resistance and Obesity : a Case-Control Study in a Javanese Population / Rini Arianti, Nia Lukita Ariani, Al Azhar Muhammad, Ahmad Hamim Sadewa, Arta Farmawati, Sunarti, Pramudji Hastuti, Endre Kristóf
Dátum:2021
ISSN:2075-1729
Megjegyzések:Single nucleotide polymorphisms (SNPs) in obesity-related genes, such as ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) and adiponectin (ADIPOQ), potentially increase the risk of insulin resistance, the most common metabolic dysregulation related to obesity. We investigated the association of ENPP1 SNP K121Q (rs1044498) with insulin resistance and ADIPOQ SNP + 267G > T (rs1501299) with circulating adiponectin levels in a case?control study involving 55 obese and 55 lean Javanese people residing in Yogyakarta, Indonesia. Allele frequency was determined by a chi squared test or Fisher's exact test with an expected value less than 0.05. Odds ratios and 95% confidence intervals were estimated by regression logistic analysis. The presence of the Q121 allele of ENPP1 resulted in significantly higher fasting glucose, fasting insulin levels, and HOMA-IR, as compared to homozygous K121 carriers. The risk of insulin resistance was elevated in obese individuals carrying Q121 instead of homozygous K121. Adiponectin level was significantly lower in the obese group as compared to the lean group. Obese individuals carrying homozygous protective alleles (TT) of ADIPOQ tended to have lower adiponectin levels as compared to GT and GG carriers, however, we did not find statistically significant effects of the +276G > T SNP of the ADIPOQ gene on the plasma adiponectin levels or on the development of obesity.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Life. - 11 : 6 (2021), p. 552-. -
További szerzők:Ariani, Nia Lukita Muhammad, Al Azhar Sadewa, Ahmad Hamim Farmawati, Arta Sunarti Hastuti, Pramudji Kristóf Endre (1987-) (általános orvos)
Pályázati támogatás:FK131424
OTKA
EFOP-3.6.1-16-2016-00022
EFOP
ÚNKP-20-5-DE-12
Egyéb
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
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7.

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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8.

001-es BibID:BIBFORM129637
035-os BibID:(scopus)105004462224 (wos)001483772000001
Első szerző:Artika, I. Made
Cím:RNA modifications and their role in gene expression / Artika I. Made, Arianti Rini, Demény Máté Á., Kristóf Endre
Dátum:2025
ISSN:2296-889X
Megjegyzések:Post-transcriptional RNA modifications have recently emerged as critical regulators of gene expression programs. Understanding normal tissue development and disease susceptibility requires knowledge of the various cellular mechanisms which control gene expression in multicellular organisms. Research into how different RNA modifications such as in N6 methyladenosine (m6A), inosine (I), 5-methylcytosine (m5C), pseudouridine (?), 5-hydroxymethylcytosine (hm5C), N1-methyladenosine (m1A), N6,2·-O dimethyladenosine (m6Am), 2·-O-methylation (Nm), N7-methylguanosine (m7G) etc. affect the expression of genes could be valuable. This review highlights the current understanding of RNA modification, methods used to study RNAmodification, types of RNA modification, and molecular mechanisms underlying RNA modification. The role of RNA modification in modulating gene expression in both physiological and diseased states is discussed. The potential applications of RNA modification in therapeutic development are elucidated.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
RNA
RNA modification
epitranscriptomics
gene expression
RNA editing
therapeutic development
Megjelenés:Frontiers in Molecular Biosciences. - 12 (2025), p. 1-19. -
További szerzők:Arianti, Rini (1991-) (biokémikus) Demény Máté Ágoston (1976-) (molekuláris biológus) Kristóf Endre (1987-) (általános orvos)
Pályázati támogatás:FK145866
OTKA
K147482
OTKA
PD146202
OTKA
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

9.

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:

10.

001-es BibID:BIBFORM116986
035-os BibID:(WoS)001113744200011 (Scopus)85180004955
Első szerző:Huang, Zan
Cím:Supraclavicular brown adipocytes originate from Tbx1+ myoprogenitors / Huang Zan, Gu Chenxin, Zhang Zengdi, Arianti Rini, Swaminathan Aneesh, Tran Kevin, Battist Alex, Kristóf Endre, Ruan Hai-Bin
Dátum:2023
ISSN:1544-9173 1545-7885
Megjegyzések:Brown adipose tissue (BAT) dissipates energy as heat, contributing to temperature control, energy expenditure, and systemic homeostasis. In adult humans, BAT mainly exists in supraclavicular areas and its prevalence is associated with cardiometabolic health. However, the developmental origin of supraclavicular BAT remains unknown. Here, using genetic cell marking in mice, we demonstrate that supraclavicular brown adipocytes do not develop from the Pax3(+)/Myf5(+) epaxial dermomyotome that gives rises to interscapular BAT (iBAT). Instead, the Tbx1(+) lineage that specifies the pharyngeal mesoderm marks the majority of supraclavicular brown adipocytes. Tbx1(Cre)-mediated ablation of peroxisome proliferator-activated receptor gamma (PPAR gamma) or PR/SET Domain 16 (PRDM16), components of the transcriptional complex for brown fat determination, leads to supraclavicular BAT paucity or dysfunction, thus rendering mice more sensitive to cold exposure. Moreover, human deep neck BAT expresses higher levels of the TBX1 gene than subcutaneous neck white adipocytes. Taken together, our observations reveal location-specific developmental origins of BAT depots and call attention to Tbx1(+) lineage cells when investigating human relevant supraclavicular BAT.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Plos Biology. - 21 : 12 (2023), p. 1-19. -
További szerzők:Gu, Chenxin Zhang, Zengdi Arianti, Rini (1991-) (biokémikus) Swaminathan, Aneesh Tran, Kevin Battist, Alex Kristóf Endre (1987-) (általános orvos) Ruan, Hai-Bin
Pályázati támogatás:FK131424
OTKA
Internet cím:Szerző által megadott URL
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Intézményi repozitóriumban (DEA) tárolt változat
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11.

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:

12.

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:
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