{"doi":"10.1101/2020.08.20.256487","title":"4β-hydroxycholesterol is a pro-lipogenic factor that promotes SREBP1c expression and activity through Liver X-receptor","abstract":"Oxysterols are oxidized derivatives of cholesterol that play signaling roles in lipid biosynthesis and homeostasis. Here we show that 4β-hydroxycholesterol (4β-HC), a liver and serum abundant oxysterol of poorly defined function, is a potent and selective inducer of the master lipogenic transcription factor, Sterol Regulatory Element Binding Protein 1c (SREBP1c), but not the related steroidogenic transcription factor SREBP2. Mechanistically, 4β-HC acts as a putative agonist for Liver X receptor (LXR), a sterol sensor and transcriptional regulator previously linked to SREBP1c activation. Unique among the oxysterol agonists of LXR, 4β-HC induced expression of the lipogenic program downstream of SREBP1c, and triggered de novo lipogenesis both in primary hepatocytes and in mouse liver. 4β-HC-acted in parallel to insulin-PI3K-dependent signaling to stimulate triglyceride synthesis and lipid droplet accumulation. Thus, 4β-HC is an endogenous regulator of de novo lipogenesis through the LXR-SREBP1c axis.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":130807,"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":0.957,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":284991,"name":"Peter‐James H. Zushin","orcid":"0000-0002-1915-2181","position":1,"is_corresponding":false},{"id":34045,"name":"Charles A. Berdan","orcid":null,"position":2,"is_corresponding":false},{"id":583607,"name":"Robert J. van Eijkeren","orcid":"0000-0002-0443-299X","position":3,"is_corresponding":false},{"id":308930,"name":"Xuntian Jiang","orcid":"0000-0001-9048-7294","position":4,"is_corresponding":false},{"id":270698,"name":"Mingxing Qian","orcid":"0000-0002-2106-2855","position":5,"is_corresponding":false},{"id":310078,"name":"Daniel S. Ory","orcid":null,"position":6,"is_corresponding":false},{"id":246033,"name":"Douglas F. Covey","orcid":"0000-0002-9316-8683","position":7,"is_corresponding":false},{"id":34058,"name":"Daniel K. Nomura","orcid":"0000-0003-1614-8360","position":8,"is_corresponding":false},{"id":576823,"name":"Andreas Stahl","orcid":"0000-0002-9096-3024","position":9,"is_corresponding":false},{"id":583608,"name":"Ethan J. Weiss","orcid":"0000-0001-9936-5816","position":10,"is_corresponding":false},{"id":246377,"name":"Roberto Zoncu","orcid":"0000-0003-1611-1891","position":11,"is_corresponding":false},{"id":584038,"name":"Ofer Moldavski","orcid":null,"position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-18T23:15:56.698770Z","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":[]}