Role of Non-Coding RNAs in White and Brown Adipose Tissue Differentiation and Development
Abstract
:1. Introduction
2. White vs. Brown Adipose Tissue
2.1. White Adipose Tissue (WAT)
2.2. Brown Adipose Tissue (BAT)
3. Stem Cells and Adipose Tissue Plasticity
3.1. Adipose-Derived Stem Cells (ADSCs)
3.2. Adipogenic Differentiation Potential
4. Transcription Factors Involved in WAT and BAT Development
5. miRNAs as Key Genetic Regulators
5.1. miRNAs Involved in the Differentiation and Function of WAT
5.1.1. Positive WAT Regulators
5.1.2. Negative WAT Regulators
5.2. miRNAs Involved in the Differentiation and Function of BAT
5.2.1. Positive BAT Regulators
5.2.2. Negative BAT Regulators
6. Other Non-Coding RNA Molecules Involved in the Differentiation and Function of WAT and BAT
6.1. Long Non-Coding RNAs (lncRNAs)
6.2. Circular RNAs (circRNAs)
7. Future Perspectives of Non-Coding RNAs as Potential Therapeutic Targets
8. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Differentiation Stage | Key miRNA Regulators | Target Gene(s) | Outcome | Reference(s) |
---|---|---|---|---|
Cell fate determination | miR-30a/d, miR-204, miR-320 | RUNX2 | promote adipogenesis | [62,63,64] |
miR-17, miR-106a | BMP2 | promote adipogenesis | [65] | |
miR-194 | HDAC6 | inhibits adipogenesis | [66] | |
miR-637 | Osterix | promotes adipogenesis | [67] | |
Clonal expansion | miR-17-92 cluster | RB2/p130 | promotes adipogenesis | [68] |
miR-363, miR-93 | E2F3, TBX3 | inhibit adipogenesis | [69,70] | |
let-7 | HMGA2 | inhibits adipogenesis | [71] | |
miR-33b | HMGA2 | inhibits adipogenesis | [72] | |
miR-146b | KLF7 | promotes adipogenesis | [73] | |
Terminal differentiation | miR-130 | PPARγ | inhibits adipogenesis | [74,75] |
hsa-miR-138 | EID-1 | inhibits adipogenesis | [76] | |
miR-21 | TGFBR2 | promotes adipogenesis | [77] | |
miR-143 | PTN, ERK5 | promotes adipogenesis | [78] | |
miR-148a | WNT1 | promotes adipogenesis | [78,79] | |
miR-210 | TCF712 | promotes adipogenesis | [80] | |
miR-344, miR-709 | GSK3β | inhibit adipogenesis | [81,82] | |
miR-146b | SIRT1 | promotes adipogenesis | [83] | |
miR-93 | SIRT7 | inhibits adipogenesis | [70] |
miRNA | Function(s) | Target Gene(s) | Reference(s) | |
---|---|---|---|---|
Positive regulators of brown adipogenesis | miR-26 | impairs the browning process upon its repression regulates the expression of metalloproteinase ADAM17 | UCP1, PPARγ, FABP3, ADRB1, PRDM16 | [109] |
miR-129 | regulates thermogenesis and energy expenditure represents a potential obesity biomarker | IGF2, EGR1, ATG7 | [110,111] | |
miR-328 | favors BAT differentiation and increases C/EBPβ, UCP1 levels, and oxygen consumption impairs muscle progenitor commitment by regulating the switch between myogenic and brown adipogenic lineages | BACE1 | [112] | |
miR-378 | regulates cAMP turnover in BAT and enhances brown adipocyte differentiation stimulates lipolysis | PDE1b | [113,114] | |
miR-455 | enhances thermogenic capacity in response to cold controls brown adipogenesis represents a potential therapeutic target for human metabolic disorders | HIF1an, Cidea, RUNX1t1, NDN PPARγ, C/EBPα, and C/EBPδ, UCP1, PRDM16 | [115] | |
Negative regulators of brown adipogenesis | miR-27b | increases expression of specific BAT markers (such as UCP1, PRMD16, PGC1α) upon its knockdown reduces energy expenditure and increases fat accumulation | PPARδ, prohibitin, PRDM16, UCP1 | [116,117] |
miR-34a | reduces adiposity, improves serum levels, and increases oxidative function upon its blockage | CD137, UCP1 | [118] | |
miR-106b-93 cluster | plays a role in energy homeostasis increased expression in obesity | UCP1, PRDM16, Cidea, PPARα, PPARγ, PGC1α, FABP4, adiponectin | [70] | |
miR-133 | inhibits BAT differentiation | PRDM16 | [119,120] |
miRNA | Function(s) | Target Gene(s) | Reference(s) | |
---|---|---|---|---|
Positive regulators of white adipogenesis | miR-148a-3p | promotes WAT differentiation upregulates mRNA and protein levels of PPARγ, C/EBPα, and FABP4 enhances intracellular triglyceride content contains a functional CREB domain | PTEN, WNT1 | [79,92] |
miR-181a | promotes adipocyte differentiation accelerates the accumulation of lipid droplets and the synthesis of triglycerides represses TNFα function (a cytokine involved in regulating lipogenesis) | TNFα | [85] | |
miR-375 | enhances adipogenic differentiation increases mRNA levels of C/EBPα, PPARγ2 induces the accumulation of Ap2 and triglyceride suppresses ERK1/2 phosphorylation levels | ERK1/2 | [84] | |
miR-26b-5p | promotes adipocyte differentiation increases levels of lipid deposition and adipogenic-related marker genes dowregulates significantly FGF21 mRNA expression | FGF21 | [93] | |
Negative regulators of white adipogenesis | miR-377-3p | decreases adipogenic differentiation downregulates expression of key-adipogenic markers (such as PPARγ, C/EBPα, and AP2) reduces intracellular lipid droplet accumulation | LIFR | [94] |
miR-182 | impairs WAT differentiation suppresses the synthesis of lipid droplets inhibits the expression of adipogenic-related markers (such as C/EBPβ, PPARγ, adiponectin, and SREBP1) represses glucocorticoid-induced expression of C/EBPα | C/EBPα | [95] | |
miR-27a | inhibits adipocyte differentiation by reducing the expression of key adipogenic regulator PPARγ decreases lipid accumulation represses mRNA expression levels of AP2, LPL, CD36, and adiponectin | PPARγ | [96] | |
hsa-miR-138 | inhibits adipogenic differentiation reduces lipid droplet synthesis and accumulation decreases the expression of C/EBPα, PPARγ, LPL, adiponectin, and FABP4 | EID-1 | [76] |
lncRNA | Function(s) | Target miRNA/Gene(s) | Reference | |
---|---|---|---|---|
Positive regulators of white adipogenesis | lncRNA-Acart | regulates preadipocyte differentiation and proliferation decreases cellular apoptosis | PPARγ | [129] |
PU.1 AS lncRNA | promotes adipogenesis through the formation of a sense-antisense RNA duplex with PU.1 mRNA | PPARγ, FASN | [130] | |
lncRNA-SRA | enhances adipogenic differentiation increases glucose uptake and phosphorylation of AKT and FOXO1 in response to insulin stimulates IGF-1 signaling and inhibits phosphorylation of MAPK and JNK during early differentiation stages | AKT, FOXO1 | [131] | |
lncRNA-lncIMF2 | promotes proliferation and adipogenic differentiation acts as a molecular sponge for miR-217 regulates the expression of specific adipogenic marker genes | PPARγ, ATGl | [132] | |
lncRNA-MIR31HG | favors adipocyte lineage commitment in vitro and in vivo regulates the expression of active histone markers H3K4me3 and AcH3 in the promoter region of FABP4 suppresses WNT/β-catenin pathway | FABP4 | [133] | |
lncRNA-slincRAD | promotes early adipogenesis by allowing the commitment of growth-arrested cells into the cell cycle through hormone induction guides epigenetic factors to mediate the methylation of cyclin-dependent kinase inhibitor p21 promoter | DNMT1 | [134] | |
lncRNA-ADINR | promotes adipogenic differentiation by modulating transcription of C/EBPα in cis and recruiting MLL3/4 histone methyltransferase complex increases H3K4me3 and decreases H3K27me3 histone modification in the C/EBPα locus | PA1 | [135] | |
Negative regulators of white adipogenesis | lncRNA-H19 | inhibits adipogenic commitment of cells through epigenetic modulation of histone deacetylases forms a complex with miR-675 | CTCF | [36] |
adipoQ (adiponectin) AS lncRNA | inhibits white adipose tissue formation through its transfer from the nucleus to the cytoplasm forms a complex with adipoQ mRNA and suppresses its translation | adipoQ mRNA | [136] | |
lncRNA-CAAlnc1 | impairs adipogenesis blocks the binding of HuR to adipogenic transcription factor mRNAs and decreases the expression of these factors | HuR | [137] | |
lncRNA-ADNCR | inhibits adipocyte differentiation functions as a competing endogenous RNA (ceRNA) for miR-204 promotes SIRT1 upregulation (gene implicated in inhibiting adipogenic gene expression by targeting PPARγ activity) | miR-204 | [138] | |
LncRNA-Bmncr | impairs white adipogenesis by serving as a scaffold to allow the interaction of TAZ and ABL facilitates TAZ-RUNX2/PPARγ transcriptional complex assembly | PPARγ | [139] | |
Positive regulator of brown adipogenesis | lncRNA-XIST | regulates brown adipocyte differentiation controls metabolic disorders by preventing high-fat diet-induced obesity | C/EBPα | [140] |
lncRNA-BATE1 | promotes brown adipogenesis by binding to the heterogeneous ribonucleoprotein U plays a significant function in thermogenesis regulates the expression of a set of genes related to brown adipogenesis and mitochondrial biogenesis and function | PPARγ, C/EBPα, C/EBPβ | [141] | |
lncRNA-BATE10 | favors full brown fat differentiation and development plays a role in the browning of white fat downregulates respiratory electron transport at the genome level decreases significantly the expression of selective-BAT marker genes upon its knockdown competes with PGC1α mRNA for the binding of CELF1 during BAT differentiation | PPARγ, C/EBPα, FABP4, PGC1α | [142] | |
lncRNA-Blnc1 | promotes brown adipogenesis by stimulating thermogenic gene expression acts by forming a ribonucleoprotein complex with hnRNPU and EBF2 | EBF2 | [143] | |
lncRNA-AK079912 | promotes brown tissue adipogenesis and WAT browning upregulates the expression of genes implicated in thermogenesis regulates lipid accumulation, mitochondrial copy number, and levels of mitochondrial ETC | PPARγ | [144] | |
Negative regulator of brown adipogenesis | lncRNA-uc.417 | impairs brown adipogenesis and attenuates the thermogenic program suppresses moderately p38MAPK signaling pathway decreases significantly the expression of BAT- and mitochondrial-related marker genes attenuates mitochondrial respiration rate | PPARγ2, C/EBPβ | [145] |
circRNA | Function(s) | Target miRNA/Gene(s) | Reference | |
---|---|---|---|---|
Positive regulators of white adipogenesis | circRNA-CDR1as | regulates positively adipogenic differentiation acts via the miRNA-7-5p-/WNT5B pathway | miRNA-7-5p, WNT5b | [178] |
circRNA-ATXN2 | promotes adipogenic differentiation increases the expression of PPARγ and C/EBPα favors lipid droplet synthesis and accumulation inhibits proliferation and promotes apoptosis | PPARγ, C/EBPα | [179] | |
Negative regulators of white adipogenesis | circRNA-FUT10 | inhibits adipocyte differentiation by sponging miRNA-let-7 promotes adipocyte proliferation | let-7c/let-e, PGC1β | [180] |
circRNA-INSR | impairs adipogenic differentiation acts via miR-152/MEOX2 pathway | miR-152 | [181] | |
Positive regulator of brown adipogenesis | circRNA-0001017 | regulates brown adipogenesis by interacting with miR-503 | miR-503 | [182] |
Negative regulator of brown adipogenesis | circRNA-Ogdh | impairs BAT differentiation promotes lipolysis by upregulating the expression of ATGL (key lipolysis protein) suppresses lipid droplet accumulation downregulates the expression of C/EBPα, C/EBPβ, PPARγ, and RXRA | miR-34a-5p, ATGL | [183] |
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Sleiman, L.; Dinescu, S. Role of Non-Coding RNAs in White and Brown Adipose Tissue Differentiation and Development. Non-Coding RNA 2025, 11, 30. https://doi.org/10.3390/ncrna11030030
Sleiman L, Dinescu S. Role of Non-Coding RNAs in White and Brown Adipose Tissue Differentiation and Development. Non-Coding RNA. 2025; 11(3):30. https://doi.org/10.3390/ncrna11030030
Chicago/Turabian StyleSleiman, Lea, and Sorina Dinescu. 2025. "Role of Non-Coding RNAs in White and Brown Adipose Tissue Differentiation and Development" Non-Coding RNA 11, no. 3: 30. https://doi.org/10.3390/ncrna11030030
APA StyleSleiman, L., & Dinescu, S. (2025). Role of Non-Coding RNAs in White and Brown Adipose Tissue Differentiation and Development. Non-Coding RNA, 11(3), 30. https://doi.org/10.3390/ncrna11030030