Pathway Human Homo sapiens

Transcriptional regulation of white adipocyte differentiation

R-HSA-381340 in Reactome release 97: under Adipogenesis, with 84 genes placed in it by the mapping files and 0 child pathways in the hierarchy.

The same number in the other species

Reactome writes the mouse and rat events it infers from a human pathway under the human number with the species token. A door opens only where that species' own list in this release holds the id: R-MMU-381340 (mouse), R-RNO-381340 (rat). Whether the event was inferred from this one is what the record says.

The record
The genes
Parents and children

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This page reads the pathway's record from its source while you read the rest; with scripts off the card stays at its loading line. Reload with scripts on to see it, or open the source's own page from the link in the card.

01The record

Reactome's own record of this pathway

What this tells you

The pathway list, the hierarchy and the genes on this page are read from the files Reactome publishes for Reactome release 97, built into this site on 2026-09-09: the pathway list, the hierarchy relationship file and the two gene mapping files. The record card is the one live read, Reactome's own record of this pathway.

Reactome's download page describes the mapping files: Mapping files link the source database identifier to the lowest level pathway diagram or subset of the pathway, all levels of the pathway hierarchy or database identifier to all reactions. [R13] The gene list here is the all-levels mapping of NCBI Gene ids, filled from the all-levels mapping of Ensembl ids where the NCBI file has no row for a gene; each row names which file it came from by the shape of its source id. Each row carries the evidence codes the file writes for it, as written and unranked, and both where the file writes both; no page of Reactome's documentation the survey read defines the codes, so this page does not expand them. A gene id the identity files do not name is kept as the source's own id with no door rather than turned into a symbol.

On citing what a search finds, Reactome says: It should be remembered that while we strive to contain the most current and accurate data, Reactome should not be used in citations where other primary sources of information are available. [R12] The record card prints the literature Reactome attaches to a curated pathway for that reason. The data are public domain: All data in the Reactome database and files derived from that data are licensed under the Creative Commons Public Domain Dedication (CC0). User may copy, modify, and distribute these data, even for commercial purposes, without asking for permission. Attribution is encouraged but not required. [R10] The pathway illustrations are licensed apart, under CC BY 4.0, and none is shown here.

A gene on this list is one Reactome places in this pathway in this release, and that is all the row says: it does not say the gene is expressed in a tissue or associated with a disease, which are the other two explorers' questions, read from other sources. Reactome's papers of record are [R01] [R02].

[R01] Ragueneau E, Gong C, Sinquin P, Sevilla C, Beavers D, Grentner A, et al. (2026). The Reactome Knowledgebase 2026. Nucleic Acids Research 54:D673-D681. PMID 41251150, doi 10.1093/nar/gkaf1223.
[R02] Milacic M, Beavers D, Conley P, Gong C, Gillespie M, Griss J, et al. (2024). The Reactome Pathway Knowledgebase 2024. Nucleic Acids Research 52:D672-D678. PMID 37941124, doi 10.1093/nar/gkad1025.
[R10] Reactome, reactome.org. License Agreement. https://reactome.org/license, read 2026-09-09.
[R12] Reactome, reactome.org. Citing us. https://reactome.org/cite, read 2026-09-09.
[R13] Reactome, reactome.org. Download. https://reactome.org/download-data, read 2026-09-09.

Stable id: R-HSA-381340.5
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2011-03-15
Last updated: 2022-06-09
Events inside: 19, counted from the record

Adipogenesis is the process of cell differentiation by which preadipocytes become adipocytes. During this process the preadipocytes cease to proliferate, begin to accumulate lipid droplets and develop morphologic and biochemical characteristics of mature adipocytes such as hormone responsive lipogenenic and lipolytic programs. The most intensively studied model system for adipogenesis is differentiation of the mouse 3T3-L1 preadipocyte cell line by an induction cocktail of containing mitogens (insulin/IGF1), glucocorticoid (dexamethasone), an inducer of cAMP (IBMX), and fetal serum (Cao et al. 1991, reviewed in Farmer 2006). More recently additional cellular models have become available to study adipogenesis that involve almost all stages of development (reviewed in Rosen and MacDougald 2006). In vivo knockout mice lacking putative adipogenic factors have also been extensively studied. Human pathways are traditionally inferred from those discovered in mouse but are now beginning to be validated in cellular models derived from human adipose progenitors (Fischer-Posovszky et al. 2008, Wdziekonski et al. 2011).

Adipogenesis is controlled by a cascade of transcription factors (Yeh et al. 1995, reviewed in Farmer 2006, Gesta et al. 2007). One of the first observable events during adipocyte differentiation is a transient increase in expression of the CEBPB (CCAAT/Enhancer Binding Protein Beta, C/EBPB) and CEBPD (C/EBPD) transcription factors (Cao et al. 1991, reviewed in Lane et al. 1999). This occurs prior to the accumulation of lipid droplets. However, it is the subsequent inductions of CEBPA and PPARG that are critical for morphological, biochemical and functional adipocytes.

Ectopic expression of CEBPB alone is capable of inducing substantial adipocyte differentiation in fibroblasts while CEBPD has a minimal effect. CEBPB is upregulated in response to intracellular cAMP (possibly via pCREB) and serum mitogens (possibly via Krox20). CEBPD is upregulated in response to glucocorticoids. The exact mechanisms that upregulate the CEBPs are not fully known.

CEBPB and CEBPD act directly on the Peroxisome Proliferator-activated Receptor Gamma (PPARG) gene by binding its promoter and activating transcription. CEBPB and CEBPD also directly activate the EBF1 gene (and possibly other EBFs) and KLF5 (Jimenez et al. 2007, Oishi 2005). The EBF1 and KLF5 proteins, in turn bind, and activate the PPARG promoter. Other hormones, such as insulin, affect PPARG expression and other transcription factors, such as ADD1/SREBP1c, bind the PPARG promoter. This is an area of ongoing research.

During adipogenesis the PPARG gene is transcribed to yield 2 variants. The adipogenic variant 2 mRNA encodes 30 additional amino acids at the N-terminus compared to the widely expressed variant 1 mRNA.

PPARG encodes a type II nuclear hormone receptor (remains in the nucleus in the absence of ligand) that forms a heterodimer with the Retinoid X Receptor Alpha (RXRA). The heterodimer was initially identified as a complex regulating the aP2/FABP4 gene and named ARF6 (Tontonoz et al. 1994).

The PPARG:RXRA heterodimer binds a recognition sequence that consists of two hexanucleotide motifs (DR1 motifs) separated by 1 nucleotide. Binding occurs even in the absence of ligands, such as fatty acids, that activate PPARG. In the absence of activating ligands, the PPARG:RXRA complex recruits repressors of transcription such as SMRT/NCoR2, NCoR1, and HDAC3 (Tontonoz and Spiegelman 2008).

Each molecule of PPARG can bind 2 molecules of activating ligands. Although, the identity of the endogenous ligands of PPARG is unknown, exogenous activators include fatty acids and the thiazolidinedione class of antidiabetic drugs (reviewed in Berger et al. 2005, Heikkinen et al. 2007, Lemberger et al. 1996). The most potent activators of PPARG in vitro are oxidized derivatives of unsaturated fatty acids.. Upon binding activating ligands PPARG causes a rearrangement of adjacent factors: Corepressors such as SMRT/NCoR2 are lost and coactivators such as TIF2, PRIP, CBP, and p300 are recruited (Tontonoz and Spiegelman). PPARG also binds directly to the TRAP220 subunit of the TRAP/Mediator complex that recruits RNA polymerase II. Thus binding of activating ligand by PPARG causes transcription of PPARG target genes.

Targets of PPARG include genes involved in differentiation (PGAR/HFARP, Perilipin, aP2/FABP4, CEBPA), fatty acid transport (LPL, FAT/CD36), carbohydrate metabolism (PEPCK-C, AQP7, GK, GLUT4 (SLC2A4)), and energy homeostasis (LEPTIN and ADIPONECTIN) (Perera et al. 2006).

Within 10 days of differentiation CEBPB and CEBPD are no longer located at the PPARG promoter. Instead CEBPA is present. EBF1 and PPARG bind the CEBPA promoter and activate transcription of CEBPA, one of the key transcription factors in adipogenesis. A current hypothesis posits a self-reinforcing loop that maintains PPARG expression and the differentiated state: PPARG activates CEBPA and CEBPA activates PPARG. Additionally EBF1 (and possibly other EBFs) activates CEBPA, CEBPA activates EBF1, and EBF1 activates PPARG.

Literature Reactome attaches

Fat and beyond: the diverse biology of PPARgammaAnnu Rev Biochem, 2008, vol. 77, p. 289-312PubMed 18518822
Transcriptional control of adipocyte formationCell Metab, 2006, vol. 4, p. 263-73PubMed 17011499
Developmental origin of fat: tracking obesity to its sourceCell, 2007, vol. 131, p. 242-56PubMed 17956727
PPARs: therapeutic targets for metabolic diseaseTrends Pharmacol Sci, 2005, vol. 26, p. 244-51PubMed 15860371
PPARgamma in human and mouse physiologyBiochim Biophys Acta, 2007, vol. 1771, p. 999-1013PubMed 17475546
Peroxisome proliferator-activated receptors: a nuclear receptor signaling pathway in lipid physiologyAnnu Rev Cell Dev Biol, 1996, vol. 12, p. 335-63PubMed 8970730
Adipocyte-specific transcription factor ARF6 is a heterodimeric complex of two nuclear hormone receptors, PPAR gamma and RXR alphaNucleic Acids Res, 1994, vol. 22, p. 5628-34PubMed 7838715

Reactome's record lists 8 orthologous events, R-MMU-381340 (Mus musculus), R-RNO-381340 (Rattus norvegicus) among the species this site serves, and 6 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-09-30 ET · Reactome pathway browser"Transcriptional regulation of white adipocyte differentiation". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-381340 with StableID: R-HSA-381340.5 (accessed 2026-09-30 ET). Reactome version 97 (CC0).

Reading this pathway's record from Reactome (the pathway record).Still reading. A first read of a pathway can take a while; this page waits up to 35 seconds for it, and its scripts then bring in the panel, or a line saying what did not arrive.

02The genes

Genes Reactome places in this human pathway

The mapping files place 84 genes in this human pathway; showing 1 to 84, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 1 of 1
Gene	Authority id	Mapping file id	Evidence codes
GeneADIPOQ	AuthorityHGNC:13633	Mapping file id9370 NCBI file	EvidenceTAS
GeneADIRF	AuthorityHGNC:24043	Mapping file id10974 NCBI file	EvidenceIEA
GeneANGPTL4	AuthorityHGNC:16039	Mapping file id51129 NCBI file	EvidenceTAS
GeneCARM1	AuthorityHGNC:23393	Mapping file id10498 NCBI file	EvidenceTAS
GeneCCNC	AuthorityHGNC:1581	Mapping file id892 NCBI file	EvidenceIEA, TAS
GeneCCND3	AuthorityHGNC:1585	Mapping file id896 NCBI file	EvidenceTAS
GeneCD36	AuthorityHGNC:1663	Mapping file id948 NCBI file	EvidenceTAS
GeneCDK19	AuthorityHGNC:19338	Mapping file id23097 NCBI file	EvidenceIEA, TAS
GeneCDK4	AuthorityHGNC:1773	Mapping file id1019 NCBI file	EvidenceTAS
GeneCDK8	AuthorityHGNC:1779	Mapping file id1024 NCBI file	EvidenceIEA, TAS
GeneCEBPA	AuthorityHGNC:1833	Mapping file id1050 NCBI file	EvidenceIEA, TAS
GeneCEBPB	AuthorityHGNC:1834	Mapping file id1051 NCBI file	EvidenceIEA, TAS
GeneCEBPD	AuthorityHGNC:1835	Mapping file id1052 NCBI file	EvidenceIEA
GeneCHD9	AuthorityHGNC:25701	Mapping file id80205 NCBI file	EvidenceTAS
GeneCREBBP	AuthorityHGNC:2348	Mapping file id1387 NCBI file	EvidenceIEA, TAS
GeneEBF1	AuthorityHGNC:3126	Mapping file id1879 NCBI file	EvidenceIEA
GeneEGR2	AuthorityHGNC:3239	Mapping file id1959 NCBI file	EvidenceIEA
GeneEP300	AuthorityHGNC:3373	Mapping file id2033 NCBI file	EvidenceIEA, TAS
GeneFABP4	AuthorityHGNC:3559	Mapping file id2167 NCBI file	EvidenceIEA, TAS
GeneFAM120B	AuthorityHGNC:21109	Mapping file id84498 NCBI file	EvidenceIEA, TAS
GeneHDAC3	AuthorityHGNC:4854	Mapping file id8841 NCBI file	EvidenceIEA, TAS
GeneHELZ2	AuthorityHGNC:30021	Mapping file id85441 NCBI file	EvidenceIEA, TAS
GeneKLF4	AuthorityHGNC:6348	Mapping file id9314 NCBI file	EvidenceIEA
GeneKLF5	AuthorityHGNC:6349	Mapping file id688 NCBI file	EvidenceIEA
GeneLEP	AuthorityHGNC:6553	Mapping file id3952 NCBI file	EvidenceTAS
GeneLPL	AuthorityHGNC:6677	Mapping file id4023 NCBI file	EvidenceTAS
GeneMED1	AuthorityHGNC:9234	Mapping file id5469 NCBI file	EvidenceIEA, TAS
GeneMED10	AuthorityHGNC:28760	Mapping file id84246 NCBI file	EvidenceIEA, TAS
GeneMED11	AuthorityHGNC:32687	Mapping file id400569 NCBI file	EvidenceIEA, TAS
GeneMED12	AuthorityHGNC:11957	Mapping file id9968 NCBI file	EvidenceIEA, TAS
GeneMED13	AuthorityHGNC:22474	Mapping file id9969 NCBI file	EvidenceIEA, TAS
GeneMED13L	AuthorityHGNC:22962	Mapping file id23389 NCBI file	EvidenceIEA, TAS
GeneMED14	AuthorityHGNC:2370	Mapping file id9282 NCBI file	EvidenceIEA, TAS
GeneMED15	AuthorityHGNC:14248	Mapping file id51586 NCBI file	EvidenceIEA, TAS
GeneMED16	AuthorityHGNC:17556	Mapping file id10025 NCBI file	EvidenceIEA, TAS
GeneMED17	AuthorityHGNC:2375	Mapping file id9440 NCBI file	EvidenceIEA, TAS
GeneMED18	AuthorityHGNC:25944	Mapping file id54797 NCBI file	EvidenceIEA, TAS
GeneMED19	AuthorityHGNC:29600	Mapping file id219541 NCBI file	EvidenceIEA, TAS
GeneMED20	AuthorityHGNC:16840	Mapping file id9477 NCBI file	EvidenceIEA, TAS
GeneMED21	AuthorityHGNC:11473	Mapping file id9412 NCBI file	EvidenceIEA, TAS
GeneMED22	AuthorityHGNC:11477	Mapping file id6837 NCBI file	EvidenceIEA, TAS
GeneMED23	AuthorityHGNC:2372	Mapping file id9439 NCBI file	EvidenceIEA, TAS
GeneMED24	AuthorityHGNC:22963	Mapping file id9862 NCBI file	EvidenceIEA, TAS
GeneMED25	AuthorityHGNC:28845	Mapping file id81857 NCBI file	EvidenceIEA, TAS
GeneMED26	AuthorityHGNC:2376	Mapping file id9441 NCBI file	EvidenceIEA, TAS
GeneMED27	AuthorityHGNC:2377	Mapping file id9442 NCBI file	EvidenceIEA, TAS
GeneMED28	AuthorityHGNC:24628	Mapping file id80306 NCBI file	EvidenceIEA, TAS
GeneMED29	AuthorityHGNC:23074	Mapping file id55588 NCBI file	EvidenceIEA, TAS
GeneMED30	AuthorityHGNC:23032	Mapping file id90390 NCBI file	EvidenceIEA, TAS
GeneMED31	AuthorityHGNC:24260	Mapping file id51003 NCBI file	EvidenceIEA, TAS
GeneMED4	AuthorityHGNC:17903	Mapping file id29079 NCBI file	EvidenceIEA, TAS
GeneMED6	AuthorityHGNC:19970	Mapping file id10001 NCBI file	EvidenceIEA, TAS
GeneMED7	AuthorityHGNC:2378	Mapping file id9443 NCBI file	EvidenceIEA, TAS
GeneMED8	AuthorityHGNC:19971	Mapping file id112950 NCBI file	EvidenceIEA, TAS
GeneMED9	AuthorityHGNC:25487	Mapping file id55090 NCBI file	EvidenceIEA, TAS
GeneNCOA1	AuthorityHGNC:7668	Mapping file id8648 NCBI file	EvidenceIEA, TAS
GeneNCOA2	AuthorityHGNC:7669	Mapping file id10499 NCBI file	EvidenceIEA, TAS
GeneNCOA3	AuthorityHGNC:7670	Mapping file id8202 NCBI file	EvidenceIEA, TAS
GeneNCOA6	AuthorityHGNC:15936	Mapping file id23054 NCBI file	EvidenceTAS
GeneNCOR1	AuthorityHGNC:7672	Mapping file id9611 NCBI file	EvidenceIEA, TAS
GeneNCOR2	AuthorityHGNC:7673	Mapping file id9612 NCBI file	EvidenceIEA, TAS
GeneNFKB1	AuthorityHGNC:7794	Mapping file id4790 NCBI file	EvidenceIEA
GeneNR2F2	AuthorityHGNC:7976	Mapping file id7026 NCBI file	EvidenceIEA
GenePCK1	AuthorityHGNC:8724	Mapping file id5105 NCBI file	EvidenceTAS
GenePLIN1	AuthorityHGNC:9076	Mapping file id5346 NCBI file	EvidenceTAS
GenePPARA	AuthorityHGNC:9232	Mapping file id5465 NCBI file	EvidenceTAS
GenePPARG	AuthorityHGNC:9236	Mapping file id5468 NCBI file	EvidenceIEA, TAS
GenePPARGC1A	AuthorityHGNC:9237	Mapping file id10891 NCBI file	EvidenceIEA, TAS
GeneRELA	AuthorityHGNC:9955	Mapping file id5970 NCBI file	EvidenceIEA
GeneRXRA	AuthorityHGNC:10477	Mapping file id6256 NCBI file	EvidenceIEA, TAS
GeneSLC2A4	AuthorityHGNC:11009	Mapping file id6517 NCBI file	EvidenceTAS
GeneSMARCD3	AuthorityHGNC:11108	Mapping file id6604 NCBI file	EvidenceTAS
GeneSREBF1	AuthorityHGNC:11289	Mapping file id6720 NCBI file	EvidenceIEA
GeneSREBF2	AuthorityHGNC:11290	Mapping file id6721 NCBI file	EvidenceIEA
GeneTBL1X	AuthorityHGNC:11585	Mapping file id6907 NCBI file	EvidenceTAS
GeneTBL1XR1	AuthorityHGNC:29529	Mapping file id79718 NCBI file	EvidenceTAS
GeneTGFB1	AuthorityHGNC:11766	Mapping file id7040 NCBI file	EvidenceIEA
GeneTGS1	AuthorityHGNC:17843	Mapping file id96764 NCBI file	EvidenceTAS
GeneTHRAP3	AuthorityHGNC:22964	Mapping file id9967 NCBI file	EvidenceIEA, TAS
GeneTNF	AuthorityHGNC:11892	Mapping file id7124 NCBI file	EvidenceIEA
GeneWNT1	AuthorityHGNC:12774	Mapping file id7471 NCBI file	EvidenceIEA
GeneWNT10B	AuthorityHGNC:12775	Mapping file id7480 NCBI file	EvidenceIEA
GeneZNF467	AuthorityHGNC:23154	Mapping file id168544 NCBI file	EvidenceIEA
GeneZNF638	AuthorityHGNC:17894	Mapping file id27332 NCBI file	EvidenceIEA

Evidence codes on this page: IEA, TAS, as the mapping file writes them; a row carrying two was written twice by the file, once under each. The mapping file id says which file placed the gene: an NCBI Gene id from NCBI2Reactome_All_Levels.txt, an Ensembl gene id from Ensembl2Reactome_All_Levels.txt. The two files can disagree about a code, so a row's codes are the one file's view. Measured by this site's build over this release on 2026-09-09: of the 138,908 human pathway-gene pairs both files place, 207 (0.149 per cent, over 47 genes) carry TAS in the Ensembl file where the NCBI rows carry IEA alone.

Reactome mapping files, the human rows for this pathway · Reactome release 97 · read 2026-09-09 · Reactome downloads"NCBI2Reactome_All_Levels.txt" and "Ensembl2Reactome_All_Levels.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.

03The hierarchy

Parents and children in this release's hierarchy

Parents

AdipogenesisR-HSA-9843745110 genes

Children

None: no pathway of this release's list names this one as a parent.

Reactome's hierarchy is a graph rather than a tree: a pathway can sit under more than one parent, and the gene counts are each pathway's own placements at every level under it, so a parent's count is not the sum of its children's.

Reactome, the human pathway list and hierarchy relationship file · Reactome release 97 · read 2026-09-09 · Reactome downloads"ReactomePathways.txt" and "ReactomePathwaysRelation.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.