{"doi":"10.3389/fphar.2025.1645587","title":"Targeting adipocyte differentiation with CRT0066101: activation of AMPK signaling in 3T3-L1 cells","abstract":"<jats:sec><jats:title>Introduction</jats:title><jats:p>Obesity is characterized by excessive fat accumulation resulting from adipocyte hypertrophy and hyperplasia, with adipocyte differentiation being a central process driving these changes.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>The anti-adipogenic effects of CRT0066101 (CRT), a pan-protein kinase D (PKD) inhibitor, were evaluated in 3T3-L1 adipocytes. Potential drug targets of CRT were predicted using network pharmacology analysis. The expression of adipocyte-specific genes and proteins was assessed by western blotting and qRT-PCR. To examine the involvement of the AMPK pathway, cells were co-treated with CRT and the AMPK inhibitor Compound C.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>CRT significantly inhibited early-stage adipocyte differentiation, reduced lipid accumulation, and downregulated key adipogenic transcription factors, including PPARγ and C/EBPα. Mechanistically, CRT activated the AMPK pathway, a known negative regulator of adipocyte differentiation. Network pharmacology analysis further supported the involvement of AMPK in CRT’s anti-adipogenic action.</jats:p></jats:sec><jats:sec><jats:title>Discussion</jats:title><jats:p>These findings identify CRT as a novel modulator of adipocyte differentiation through AMPK activation and highlight its potential as a therapeutic candidate for obesity and metabolic syndrome.</jats:p></jats:sec>","journal":"Frontiers in Pharmacology","year":2025,"id":638203,"datarank":0.3596842909197557,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"self_citation_contribution":0.3596842909197557,"citation_network_contribution":0.0,"self_endowment_contribution":0.3596842909197557,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1039385,"name":"Ling Wang","orcid":"0000-0001-8696-676X","position":1,"is_corresponding":false},{"id":440096,"name":"Li Zhang","orcid":"0000-0003-0006-4066","position":2,"is_corresponding":false},{"id":1136950,"name":"Wenyu Tang","orcid":null,"position":3,"is_corresponding":false},{"id":1657484,"name":"Meijing Deng","orcid":null,"position":4,"is_corresponding":false},{"id":755969,"name":"Yuxin Shi","orcid":"0000-0001-8466-5920","position":5,"is_corresponding":false},{"id":1061493,"name":"Kun Xu","orcid":"0000-0003-2310-4745","position":6,"is_corresponding":false},{"id":1657487,"name":"Qingjun Wu","orcid":null,"position":7,"is_corresponding":false},{"id":1657489,"name":"Jieyang Zhao","orcid":null,"position":8,"is_corresponding":false},{"id":1657491,"name":"Jinghuan Zhang","orcid":null,"position":9,"is_corresponding":false},{"id":801787,"name":"Xin Li","orcid":"0000-0002-8779-125X","position":10,"is_corresponding":false},{"id":1248058,"name":"Jinque Luo","orcid":"0000-0002-2744-2867","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Targeting adipocyte differentiation with CRT0066101: activation of AMPK signaling in 3T3-L1 cells","abstract":"<jats:sec><jats:title>Introduction</jats:title><jats:p>Obesity is characterized by excessive fat accumulation resulting from adipocyte hypertrophy and hyperplasia, with adipocyte differentiation being a central process driving these changes.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>The anti-adipogenic effects of CRT0066101 (CRT), a pan-protein kinase D (PKD) inhibitor, were evaluated in 3T3-L1 adipocytes. Potential drug targets of CRT were predicted using network pharmacology analysis. The expression of adipocyte-specific genes and proteins was assessed by western blotting and qRT-PCR. To examine the involvement of the AMPK pathway, cells were co-treated with CRT and the AMPK inhibitor Compound C.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>CRT significantly inhibited early-stage adipocyte differentiation, reduced lipid accumulation, and downregulated key adipogenic transcription factors, including PPARγ and C/EBPα. Mechanistically, CRT activated the AMPK pathway, a known negative regulator of adipocyte differentiation. Network pharmacology analysis further supported the involvement of AMPK in CRT’s anti-adipogenic action.</jats:p></jats:sec><jats:sec><jats:title>Discussion</jats:title><jats:p>These findings identify CRT as a novel modulator of adipocyte differentiation through AMPK activation and highlight its potential as a therapeutic candidate for obesity and metabolic syndrome.</jats:p></jats:sec>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19767382","pmcid":null,"openalex_id":null,"authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://public-pages-files-2025.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1645587/pdf","host_type":"publisher"},{"url":"https://www.frontiersin.org/articles/10.3389/fphar.2025.1645587/full","host_type":"publisher"},{"url":"https://doaj.org/article/f64d444261ab48de8c302732cd62adb1","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/12392320","host_type":"repository"}],"fields_of_study":[],"mesh_terms":[],"keywords":[],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T20:17:11.655858Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}