# Dual Role of Transcription Factors in the Development and Thermogenic Function of Brown Adipose Tissue

**Authors:** Shuai Wang, Fuan Xie, Weihua Li, Wenlong Xie, Hongqiu Cheng

PMC · DOI: 10.7150/ijms.127214 · 2026-02-04

## TL;DR

This paper explores how transcription factors and other mechanisms regulate brown fat development and function, offering new strategies for treating obesity.

## Contribution

The paper highlights the dual role of transcription factors and introduces potential therapeutic strategies for obesity.

## Key findings

- Transcription factors like PPARγ and EBF2 regulate brown adipose tissue development and thermogenesis.
- AAV-based gene therapy can enhance BAT thermogenic capacity for treating obesity.
- Natural products like Artemisia argyi oil and capsaicin may safely activate BAT thermogenesis.

## Abstract

Obesity, a major global health challenge, is intricately linked to various metabolic disorders, primarily driven by an imbalance between energy intake and expenditure. Brown adipose tissue (BAT), through its unique thermogenic capability, dissipates energy as heat, playing a vital role in regulating energy homeostasis and maintaining body temperature. Recent studies have revealed a complex regulatory network involving multiple transcription factors (e.g., PPARγ, EBF2, ZFP516, FOXP1) and signaling pathways (e.g., cAMP-PKA, AMPK, mTOR), which act synergistically to finely tune the development and thermogenic function of BAT. Furthermore, gene therapy based on adeno-associated virus (AAV) vectors, which enhances the thermogenic capacity of BAT, provides a highly promising strategy for addressing obesity and metabolic disorders. Additionally, several natural product extracts including Artemisia argyi oil and capsaicin may activate BAT thermogenesis with fewer side effects, representing potential safe and effective dietary supplements for combating obesity in the future. A deeper understanding of these mechanisms may lead to novel therapeutic approaches targeting obesity and metabolic disorders, paving the way for new interventions to improve human health.

## Linked entities

- **Genes:** PPARG (peroxisome proliferator activated receptor gamma) [NCBI Gene 5468], EBF2 (EBF transcription factor 2) [NCBI Gene 64641], Zfp516 (zinc finger protein 516) [NCBI Gene 291406], FOXP1 (forkhead box P1) [NCBI Gene 27086]
- **Chemicals:** capsaicin (PubChem CID 1548943)
- **Diseases:** obesity (MONDO:0011122)

## Full-text entities

- **Genes:** Klf9 (Kruppel-like transcription factor 9) [NCBI Gene 16601] {aka 2310051E17Rik, BTEB-1, Bteb1, Gm9971}, Prdm16 (PR domain containing 16) [NCBI Gene 70673] {aka 5730557K01Rik, csp1, mel1}, Atf2 (activating transcription factor 2) [NCBI Gene 11909] {aka Atf-2, CRE-BP, Creb2, D130078H02Rik, Tg(Gzma-Klra1)7Wum, mXBP}, Myod1 (myogenic differentiation 1) [NCBI Gene 17927] {aka MYF3, MyoD, Myod-1, bHLHc1}, Bmp4 (bone morphogenetic protein 4) [NCBI Gene 12159] {aka Bmp-4, Bmp2b, Bmp2b-1, Bmp2b1}, Cebpa (CCAAT/enhancer binding protein alpha) [NCBI Gene 12606] {aka C/ebpalpha, CBF-A, Cebp}, Klf5 (Kruppel-like transcription factor 5) [NCBI Gene 12224] {aka 4930520J07Rik, Bteb2, CKLF, IKLF}, Myog (myogenin) [NCBI Gene 17928] {aka MYF4, bHLHc3, myo}, Foxp1 (forkhead box P1) [NCBI Gene 108655] {aka 3110052D19Rik, 4932443N09Rik}, Sirt3 (sirtuin 3) [NCBI Gene 64384] {aka 2310003L23Rik, Sir2l3}, Atf4 (activating transcription factor 4) [NCBI Gene 11911] {aka Atf-4, C/ATF, CREB-2, CREB2, TAXREB67}, PDGFRA (platelet derived growth factor receptor alpha) [NCBI Gene 5156] {aka CD140A, PDGFR-2, PDGFR2}, FOXP1 (forkhead box P1) [NCBI Gene 27086] {aka 12CC4, HSPC215, MFH, QRF1, hFKH1B}, Ebf2 (early B cell factor 2) [NCBI Gene 13592] {aka D14Ggc1e, EBF-2, Mmot1, O/E-3, OE-3}, Sry (sex determining region of Chr Y) [NCBI Gene 21674] {aka Tdf, Tdy}, Creb1 (cAMP responsive element binding protein 1) [NCBI Gene 12912] {aka 2310001E10Rik, 3526402H21Rik, Creb, Creb-1}, Cox8b (cytochrome c oxidase subunit 8B) [NCBI Gene 12869] {aka Cox8h, CoxVIII-H}, Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, PPARG (peroxisome proliferator activated receptor gamma) [NCBI Gene 5468] {aka CIMT1, FPLD3, GLM1, NR1C3, PPARG1, PPARG2}, Myf6 (myogenic factor 6) [NCBI Gene 17878] {aka MRF4, bHLHc4, herculin}, Glp1r (glucagon-like peptide 1 receptor) [NCBI Gene 14652] {aka GLP-1R, GLP1Rc}, Sirt6 (sirtuin 6) [NCBI Gene 50721] {aka 2810449N18Rik, Sir2l6, mSIRT6}, Gata6 (GATA binding protein 6) [NCBI Gene 14465] {aka GATA-6}, Cox5b (cytochrome c oxidase subunit 5B) [NCBI Gene 12859], Sirt2 (sirtuin 2) [NCBI Gene 64383] {aka 5730427M03Rik, SIR2L2, Sir2l}, Tle3 (transducin-like enhancer of split 3) [NCBI Gene 21887] {aka 2610103N05Rik, ESG, Grg3a, Grg3b, mKIAA1547}, PRKAA1 (protein kinase AMP-activated catalytic subunit alpha 1) [NCBI Gene 5562] {aka AMPK, AMPK alpha 1, AMPKa1}, Pax7 (paired box 7) [NCBI Gene 18509] {aka Pax-7}, Foxo1 (forkhead box O1) [NCBI Gene 56458] {aka Afxh, FKHR, Fkhr1, Foxo1a}, MYH11 (myosin heavy chain 11) [NCBI Gene 4629] {aka AAT4, FAA4, SMHC, SMMHC, SMMS-1, VSCM2}, baf (b-associated fitness) [NCBI Gene 12016], Ehmt1 (euchromatic histone methyltransferase 1) [NCBI Gene 77683] {aka 9230102N17Rik, D330003E03, Eu-HMTase1, GLP, GLP1, KMT1D}, Cldn1 (claudin 1) [NCBI Gene 12737], Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 21803] {aka TGF-beta1, TGFbeta1, Tgfb, Tgfb-1}, Cebpd (CCAAT/enhancer binding protein delta) [NCBI Gene 12609] {aka c/EBPdelta}, Ucp1 (uncoupling protein 1 (mitochondrial, proton carrier)) [NCBI Gene 22227] {aka Slc25a7, Ucp}, Cebpb (CCAAT/enhancer binding protein beta) [NCBI Gene 12608] {aka C/EBPbeta, CRP2, IL-6DBP, LAP, LIP, NF-IL6}, Klf15 (Kruppel-like transcription factor 15) [NCBI Gene 66277] {aka 1810013I09Rik, CKLF, KKLF, hlb444}, Cox7a1 (cytochrome c oxidase subunit 7A1) [NCBI Gene 12865] {aka COX7A, COX7AH, COX7AM}, Ctnnb1 (catenin beta 1) [NCBI Gene 12387] {aka Bfc, Catnb, Mesc}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, Camp (cathelicidin antimicrobial peptide) [NCBI Gene 12796] {aka CAP18, CLP, Cnlp, Cramp, FALL39, MCLP}, EBF2 (EBF transcription factor 2) [NCBI Gene 64641] {aka COE2, EBF-2, O/E-3, OE-3}, Klf3 (Kruppel-like transcription factor 3 (basic)) [NCBI Gene 16599] {aka 9930027G08Rik, Bklf, Tef-2}, Sox4 (SRY (sex determining region Y)-box 4) [NCBI Gene 20677] {aka Sox-4}, Sirt5 (sirtuin 5) [NCBI Gene 68346] {aka 0610012J09Rik, 1500032M05Rik}, Sirt1 (sirtuin 1) [NCBI Gene 93759] {aka SIR2L1, Sir2, Sir2a, Sir2alpha}, Adrb3 (adrenergic receptor, beta 3) [NCBI Gene 11556] {aka Adrb-3, beta 3-AR}, Myf5 (myogenic factor 5) [NCBI Gene 17877] {aka B130010J22Rik, Myf-5, bHLHc2}, Klf2 (Kruppel-like transcription factor 2 (lung)) [NCBI Gene 16598] {aka Lklf}, En1 (engrailed 1) [NCBI Gene 13798] {aka En-1, Mo-en.1, engrailed-1}, PRDM16 (PR/SET domain 16) [NCBI Gene 63976] {aka CMD1LL, KMT8F, LVNC8, MEL1, PFM13}, Bmp8a (bone morphogenetic protein 8a) [NCBI Gene 12163] {aka Bmp7r1, OP-2, OP2}, Bmp7 (bone morphogenetic protein 7) [NCBI Gene 12162] {aka OP1}, CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, Ddb1 (damage specific DNA binding protein 1) [NCBI Gene 13194] {aka 127kDa, p127-Ddb1}, Ppargc1a (peroxisome proliferative activated receptor, gamma, coactivator 1 alpha) [NCBI Gene 19017] {aka A830037N07Rik, Gm11133, PGC-1, PPARGC-1-alpha, Pgc-1alpha, Pgc1}, Ckm (creatine kinase, muscle) [NCBI Gene 12715] {aka CPK-M, Ckmm, M-CK, MCK}, PPARGC1A (PPARG coactivator 1 alpha) [NCBI Gene 10891] {aka LEM6, PGC-1(alpha), PGC-1alpha, PGC-1v, PGC1, PGC1A}, Esrra (estrogen related receptor, alpha) [NCBI Gene 26379] {aka ERRalpha, Err1, Estrra, Nr3b1}
- **Diseases:** hyperplasia (MESH:D006965), type 2 diabetes (MESH:D003924), nausea, vomiting (MESH:D020250), hypertrophy (MESH:D006984), cardiovascular diseases (MESH:D002318), insulin resistance (MESH:D007333), gastrointestinal side effects (MESH:D064420), weight (MESH:D015431), metabolic diseases (MESH:D008659), Obesity (MESH:D009765), weight gain resistance (MESH:D015430), diarrhea (MESH:D003967), cancer (MESH:D009369), caloric loss (MESH:D016388)
- **Chemicals:** NAD+ (MESH:D009243), glucose (MESH:D005947), Capsaicin (MESH:D002211), lipid (MESH:D008055), amino acid (MESH:D000596), NPs (MESH:D045265), fatty acid (MESH:D005227), Cat#HY-15409 (-), alpha-KG (MESH:D007656), NE (MESH:D009356), Norepinephrine (MESH:D009638), NO (MESH:D009569), empagliflozin (MESH:C570240), FFAs (MESH:D005230), TG (MESH:D014280), cGMP (MESH:D006152)
- **Species:** Artemisia argyi (species) [taxon 259893], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090], Adeno-associated virus (species) [taxon 272636]
- **Cell lines:** C2C12 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0188)

## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12964565/full.md

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Source: https://tomesphere.com/paper/PMC12964565