{"doi":"10.1101/2020.01.27.922138","title":"The Prorenin Receptor and its Soluble Form Contribute to Lipid Homeostasis","abstract":"Abstract Obesity is associated with alterations in hepatic lipid metabolism. We previously identified the prorenin receptor (PRR) as a potential contributor to liver steatosis. Therefore, we aimed to determine the relative contribution of PRR and its soluble form, sPRR, to lipid homeostasis. PRR-floxed male mice were treated with an adeno-associated virus with thyroxine-binding globulin promoter driven Cre to delete specifically PRR in hepatocytes (Liver PRR KO mice). Hepatic PRR deletion did not change the body weight but increased liver weights. Liver PRR KO mice exhibited higher plasma cholesterol levels and lower hepatic LDLR protein than control mice. Surprisingly, hepatic PRR deletion elevated hepatic cholesterol, and up-regulated hepatic SREBP2 and HMG CoA-R genes. In addition, hepatic PRR deletion increased plasma sPRR levels. In vitro studies in Hep-G2 cells demonstrated that sPRR treatment up-regulated SREBP2 suggesting that elevated plasma sPRR could contribute to hepatic cholesterol biosynthesis. Interestingly, PPARγ, PRR and total sPRR were elevated in the adipose tissue of Liver PRR KO mice suggesting that elevated plasma sPRR originated from the adipose tissue. In 3T3-L1 cells, sPRR treatment up-regulated PPARγ indicating that sPRR stimulates master regulator of adipocyte differentiation. Overall, this work support a new role for sPRR in lipid metabolism and adipose tissue – liver crosstalk.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":126187,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9552,"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":573576,"name":"Gertrude Arthur","orcid":"0000-0002-1850-1781","position":1,"is_corresponding":false},{"id":574184,"name":"Audrey Poupeau","orcid":null,"position":2,"is_corresponding":false},{"id":574185,"name":"Kellea Nichols","orcid":null,"position":3,"is_corresponding":false},{"id":516664,"name":"Brett T. Spear","orcid":"0000-0002-4343-9393","position":4,"is_corresponding":false},{"id":561221,"name":"Gregory A Graf","orcid":null,"position":5,"is_corresponding":false},{"id":573577,"name":"Ryan E. Temel","orcid":"0000-0002-9599-804X","position":6,"is_corresponding":false},{"id":533256,"name":"Frédérique Yiannikouris","orcid":"0000-0003-0584-175X","position":7,"is_corresponding":false},{"id":327434,"name":"Eva Gatineau","orcid":null,"position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-18T23:15:23.509897Z","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":[]}