Adipocyte RNA-binding protein CELF1 promotes beiging of white fat through stabilizing Dio2 mRNA
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PROVIDER: PRJNA1263392 | ENA |
REPOSITORIES: ENA
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Project description:RNA-binding proteins (RBPs) regulate diverse cellular processes at post-transcriptional level and play roles in adipocyte development. However, their involvement in the beiging of white fat remains unclear. Here we screened RBPs in inguinal adipose tissues in response to cold stimulation and identified CUG-BP Elav-like family member 1 (CELF1) as a novel regulator that promotes white fat beiging. Adipocyte-specific Celf1 deficiency impairs cold-induced beiging and reduces energy expenditure. Mechanistically, RNA immunoprecipitation RNA-seq (RIP-seq) and functional experiments revealed that CELF1 stabilizes the mRNA of the key thermogenic regulator Dio2 by binding to its 3'UTR, thereby promoting local triiodothyronine (T3) production. CELF1 augments isoproterenol-induced activation of beige adipocytes and increases mitochondria respiration capacity in vitro, and CELF1 overexpression ameliorates diet-induced obesity and metabolic dysfunction. Hence, our study identifies CELF1 as a physiological regulator of metabolic stress in activating thermogenesis and promoting energy expenditure at the post-transcriptional level, suggesting that targeting CELF1 to locally increase the T3 production may serve as a promising therapeutic strategy for combating obesity and related metabolic disorders.
2025-07-05 | GSE297248 | GEO
Project description: Not available
| S-EPMC12339685 | biostudies-literature
Project description:RNA-seq reveals the critical role of adipocyte Celf1 in cold-responsive thermogenic remodeling in inguinal white adipose tissue (iWAT). The cold-induced thermogenic program in iWAT was severely blunted in Celf1AKO mice, especially the obvious downregulation of Ucp1, Dio2, Elvol3, Tbx1, Cox7a1, and Cidea genes. The GO analysis revealed that the down-regulated genes were primarily involved in adaptive thermogenesis, temperature homeostasis, and mitochondrial-related processes, including lipid oxidation, fatty acid metabolism and so on. KEGG pathway analysis further showed that these down-regulated genes were involved in thermogenesis-related pathways, including thermogenesis, PPAR signaling, metabolic pathways, fatty acid degradation, and AMPK signaling. Together, these results suggest that adipocyte Celf1 deficiency impairs cold-induced iWAT thermogenic program.
2025-07-05 | GSE281771 | GEO
Project description:Obesity, one of the most serious public health issues, is caused by energy imbalance of energy intake and expenditure. N(6)-methyladenosine (m6A) RNA modification has been recently identified as a key regulator of obesity, while the detailed mechanism is elusive. Here, we found that YTH RNA binding protein 1 (YTHDF1), an m6A reader, acts as an essential regulator of white adipose tissue metabolism. The expression of YTHDF1 decreased in adipose tissue of mice fed a high-fat diet. Adipocyte-specific Ythdf1 deficiency exacerbated obesity-induced metabolic defects and inhibited beiging of inguinal white adipose tissue (iWAT) in mice. By contrast, mice with WAT-specific Ythdf1 overexpression were resistant to obesity and showed promotion of beiging. Mechanistically, YTHDF1 regulated the translation of diverse m6A-modified mRNAs. In particular, YTHDF1 facilitated the translation of bone morphogenetic protein 8b (Bmp8b) in an m6A-dependent manner to induce the beiging process. Together, these findings suggested that YTHDF1 may be an attractive therapeutic target for the management of obesity-associated diseases.
2023-02-02 | GSE197173 | GEO
Project description:HMGNs Regulate White Adipocyte Browning By Stabilizing Cell Identity
| PRJNA796298 | ENA
Project description:The CUG-BP and ETR-3-like factor 1 (Celf1) RNA binding protein plays an important role in heart and muscle development, and is over-expressed in the disease myotonic dystrophy. Celf1 has known roles in regulation of RNA splicing, RNA stability, and protein translation. To identify transcriptome-wide targets of the Celf1 protein in heart, we performed RNA-Seq of polyA+ RNA from mice inducibly expressing Celf1 in the heart. Mice were engineered to express the reverse tetracycline trans-activator (rtTA) from a heart-specific alpha myosin heavy chain promoter, and an N-terminal Flag-tagged version of the LYLQ isoform of human Celf1 from a tet-inducible promoter. Mice were fed doxycycline to induce Celf1 expression in heart, and hearts were harvested from 3 mice each at 12 hour, 24 hour, 72 hour, and 7 day time points. To account for potential doxycycline-dependent effects, control mice were fed doxycycline for 72 hours but these mice did not contain the tet-inducible Celf1 cassette. In total, 15 hearts were analyzed by RNA-Seq.
2014-04-01 | E-GEOD-56185 | biostudies-arrayexpress
Project description:Adaptive thermogenesis, or beiging, involves the conversion of energy-storing white adipocytes into energy-dissipating beige adipocytes, enabling physiological adaptation to environmental stressors such as hypothermia. While white and beige adipocytes share a largely similar transcriptome, this identity shift requires significant transcriptional and epigenetic reprogramming. However, the molecular mechanisms governing this transition remain incompletely understood. Here, we identify SUMOylation as a critical repressor of adipocyte beiging. Using the small-molecule SUMOylation inhibitor TAK-981, we demonstrate that transient SUMOylation inhibition primes human adipocytes to express beiging genes including UCP1 and induce mitochondrial uncoupling in a rosiglitazone-dependent manner. Furthermore, SUMOylation suppresses both the de novo differentiation of human adipose stem cells into beige adipocytes and the transdifferentiation of mature white adipocytes into beige cells. Mechanistically, TAK-981 modulates the cAMP-PKA-p38 signaling axis, ultimately affecting downstream transcriptional programs under the control of PPARG and PPARA enhancers. Our findings establish SUMOylation as a fundamental barrier to white-to-beige adipocyte reprogramming and suggest that the pharmacological combination of PPARG partial agonists with TAK-981 could promote metabolically beneficial adipose tissue remodeling in clinical settings.
2026-03-04 | GSE290926 | GEO
Project description:As a multifunctional RBP, CELF1 is known to preferentially binds to GU-rich elements (GREs) predominantly located in 3’ untranslated regions(UTRs) of target mRNA to regulate various post-transcriptional process. However, the targeted genes that regulated by CELF1 during cataractogenesis remains unknown. In present study,the function of CELF1 in SRA01/04 cells was investigated with CELF1 overexpression, the expression of MMPs was regulated by CELF1.
2022-03-23 | GSE153022 | GEO
Project description:Celf1 germline or conditional deletion mouse mutants exhibit fully penetrant lens defects including cataract. To gain insight into gene expression changes underlying these lens defects, microarray comparison was performed for lenses obtained from control and Celf1 conditional deletion mutant mice.
2023-02-18 | GSE225303 | GEO