{"doi":"10.1172/jci148545","title":"LRG1 is an adipokine that mediates obesity-induced hepatosteatosis and insulin resistance","abstract":"Dysregulation in adipokine biosynthesis and function contributes to obesity-induced metabolic diseases. However, the identities and functions of many of the obesity-induced secretory molecules remain unknown. Here, we report the identification of leucine-rich alpha-2-glycoprotein 1 (LRG1) as an obesity-associated adipokine that exacerbates high fat diet-induced hepatosteatosis and insulin resistance. Serum levels of LRG1 were markedly elevated in obese humans and mice compared with their respective controls. LRG1 deficiency in mice greatly alleviated diet-induced hepatosteatosis, obesity, and insulin resistance. Mechanistically, LRG1 bound with high selectivity to the liver and promoted hepatosteatosis by increasing de novo lipogenesis and suppressing fatty acid β-oxidation. LRG1 also inhibited hepatic insulin signaling by downregulating insulin receptor substrates 1 and 2. Our study identified LRG1 as a key molecule that mediates the crosstalk between adipocytes and hepatocytes in diet-induced hepatosteatosis and insulin resistance. Suppressing LRG1 expression and function may be a promising strategy for the treatment of obesity-related metabolic diseases.","journal":"Journal of Clinical Investigation","year":2021,"id":154321,"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":64,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9566,"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":646007,"name":"Jiyoon Ryu","orcid":"0000-0001-7365-0555","position":1,"is_corresponding":false},{"id":447817,"name":"Juanhong Liu","orcid":"0000-0002-5916-6641","position":2,"is_corresponding":false},{"id":334130,"name":"Hairong Luo","orcid":"0000-0001-7279-8152","position":3,"is_corresponding":false},{"id":654524,"name":"Ying Lv","orcid":null,"position":4,"is_corresponding":false},{"id":467723,"name":"Paul R. Langlais","orcid":"0000-0003-1929-737X","position":5,"is_corresponding":false},{"id":523530,"name":"Jie Wen","orcid":"0000-0002-3724-9905","position":6,"is_corresponding":false},{"id":646010,"name":"Feng Dong","orcid":"0000-0001-7979-5464","position":7,"is_corresponding":false},{"id":579628,"name":"Zhe Sun","orcid":"0000-0002-0634-7983","position":8,"is_corresponding":false},{"id":654525,"name":"Wenjuan Xia","orcid":null,"position":9,"is_corresponding":false},{"id":654526,"name":"Jane L. Lynch","orcid":null,"position":10,"is_corresponding":false},{"id":1050,"name":"Ravindranath Duggirala","orcid":"0000-0003-4761-597X","position":11,"is_corresponding":false},{"id":361034,"name":"Bruce J. Nicholson","orcid":"0000-0003-1649-7173","position":12,"is_corresponding":false},{"id":654527,"name":"Mengwei Zang","orcid":null,"position":13,"is_corresponding":false},{"id":464308,"name":"Yuguang Shi","orcid":"0000-0002-9979-5661","position":14,"is_corresponding":false},{"id":525231,"name":"Fang Zhang","orcid":"0000-0001-8166-9651","position":15,"is_corresponding":false},{"id":281821,"name":"Feng Liu","orcid":"0000-0002-5098-1711","position":16,"is_corresponding":false},{"id":281810,"name":"Juli Bai","orcid":"0000-0002-1193-8155","position":17,"is_corresponding":false},{"id":281820,"name":"Lily Dong","orcid":"0000-0002-6293-818X","position":18,"is_corresponding":false},{"id":557186,"name":"Sijia He","orcid":"0000-0002-1932-1141","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-18T23:43:49.684414Z","pmid":"34730111","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":[]}