{"doi":"10.1101/2021.01.11.426043","title":"TXN, a Xanthohumol Derivative, Attenuates High-Fat Diet Induced Hepatic Steatosis by Antagonizing PPARγ","abstract":"Abstract We previously reported xanthohumol (XN), and its synthetic derivative tetrahydro-XN (TXN) attenuates high-fat diet (HFD) induced obesity and metabolic syndrome in C57BL/6J mice. The objective of the current study was to determine the effect of XN and TXN on lipid accumulation in the liver. Non-supplemented mice were unable to adapt their caloric intake to 60% HFD, resulting in obesity and hepatic steatosis; however, TXN reduced weight gain and decreased hepatic steatosis. Liver transcriptomics indicated TXN might antagonize lipogenic PPARγ actions in vivo . XN and TXN inhibited rosiglitazone-induced 3T3-L1 cell differentiation concomitant with decreased expression of lipogenesis-related genes. A PPARγ competitive binding assay showed XN and TXN bind to PPARγ with an IC 50 similar to pioglitazone and 8-10 times stronger than oleate. Molecular docking simulations demonstrated XN and TXN bind in the PPARγ ligand-binding domain pocket. Our findings are consistent with XN and TXN acting as antagonists of PPARγ.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":222965,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9455,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":376789,"name":"Gerd Bobe","orcid":"0000-0002-3129-5628","position":1,"is_corresponding":false},{"id":370178,"name":"Cristobal L. Miranda","orcid":null,"position":2,"is_corresponding":false},{"id":483895,"name":"Malcolm B. Lowry","orcid":null,"position":3,"is_corresponding":false},{"id":729521,"name":"Victor L. Hsu","orcid":"0000-0002-9086-1693","position":4,"is_corresponding":false},{"id":729522,"name":"Christiane V. Löhr","orcid":"0000-0003-3787-5583","position":5,"is_corresponding":false},{"id":411967,"name":"Carmen P. Wong","orcid":"0000-0001-8294-2584","position":6,"is_corresponding":false},{"id":105409,"name":"Donald Β. Jump","orcid":"0000-0002-9473-6283","position":7,"is_corresponding":false},{"id":371804,"name":"Matthew M. Robinson","orcid":"0000-0001-7622-7357","position":8,"is_corresponding":false},{"id":29164,"name":"Thomas J. Sharpton","orcid":"0000-0002-5996-7764","position":9,"is_corresponding":false},{"id":314736,"name":"Claudia S. Maier","orcid":"0000-0003-0743-8956","position":10,"is_corresponding":false},{"id":258941,"name":"Jan F. Stevens","orcid":"0000-0002-6348-9347","position":11,"is_corresponding":false},{"id":482947,"name":"Adrian F. Gombart","orcid":"0000-0001-7830-0693","position":12,"is_corresponding":false},{"id":729520,"name":"Yang Zhang","orcid":"0000-0002-0434-931X","position":0,"is_corresponding":true}],"reference_count":89,"raw_metadata":null,"created_at":"2026-07-18T23:54:07.287704Z","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":[]}