{"doi":"10.1101/2020.06.06.137273","title":"Adipose tissue-derived neurotrophic factor 3 regulates sympathetic innervation and thermogenesis in adipose tissue","abstract":"Abstract Activation of brown fat thermogenesis increases energy expenditure and alleviates obesity. Sympathetic nervous system (SNS) is important in brown/beige adipocyte thermogenesis. Here we discover a novel fat-derived “adipokine” neurotrophic factor neurotrophin 3 (NTF3) and its receptor Tropomyosin receptor kinase C (TRKC) as key regulators of SNS growth and innervation in adipose tissue. NTF3 is highly expressed in brown/beige adipocytes, and potently stimulates sympathetic neuron neurite growth. NTF3/TRKC regulates a plethora of pathways in neuronal axonal growth and elongation. Adipose tissue sympathetic innervation is significantly increased in mice with adipocyte-specific NTF3 overexpression, but profoundly reduced in mice with TRKC haploinsufficiency (TRKC+/-). Increasing NTF3 via pharmacological or genetic approach promotes beige adipocyte development, enhances cold-induced thermogenesis and protects against diet-induced obesity (DIO); whereas TRKC+/- mice or SNS TRKC deficient mice are cold intolerant and prone to DIO. Thus, NTF3 is an important fat-derived neurotrophic factor regulating SNS innervation, energy metabolism and obesity.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":123750,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9541,"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":565540,"name":"Jia Jing","orcid":null,"position":1,"is_corresponding":false},{"id":564925,"name":"Rui Wu","orcid":"0000-0001-7229-2047","position":2,"is_corresponding":false},{"id":564924,"name":"Qiang Cao","orcid":"0000-0001-9547-9138","position":3,"is_corresponding":false},{"id":564922,"name":"Fenfen Li","orcid":"0000-0001-7247-8415","position":4,"is_corresponding":false},{"id":567198,"name":"Ke Li","orcid":"0000-0001-9599-3030","position":5,"is_corresponding":false},{"id":567199,"name":"Shirong Wang","orcid":"0000-0002-1860-2523","position":6,"is_corresponding":false},{"id":564927,"name":"Liqing Yu","orcid":"0000-0002-5186-9182","position":7,"is_corresponding":false},{"id":321278,"name":"Gary J. Schwartz","orcid":"0000-0003-0446-5553","position":8,"is_corresponding":false},{"id":249681,"name":"Huidong Shi","orcid":"0000-0003-1137-3390","position":9,"is_corresponding":false},{"id":564929,"name":"Hang Shi","orcid":"0000-0001-6472-3302","position":11,"is_corresponding":false},{"id":564928,"name":"Bingzhong Xue","orcid":"0000-0002-7857-1343","position":13,"is_corresponding":false},{"id":564923,"name":"Xin Cui","orcid":"0000-0002-2141-4400","position":0,"is_corresponding":true}],"reference_count":77,"raw_metadata":null,"created_at":"2026-07-18T23:15:03.403566Z","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":[]}