{"doi":"10.1101/2020.03.13.989442","title":"Leptin Receptors in RIP-Cre <sup>25Mgn</sup> neurons Mediate Anti-Dyslipidemia Effects of Leptin in Insulin-Deficient Male Mice","abstract":"Abstract Leptin is a potent endocrine hormone produced by adipose tissue and regulates a broad range of metabolism including glucose and lipid metabolism, with and without insulin. It is evident that central leptin signaling can lower hyperglycemia in insulin-deficient rodents via multiple mechanisms including restoration of dyslipidemia. However, the specific neurons that regulate these glucose-lowering and anti-dyslipidemia effects of leptin remain unidentified. Here we report that leptin receptors (LEPRs) in neurons expressing Cre recombinase driven by a short fragment of a promoter region of Ins2 gene (RIP-Cre 25Mgn neurons) are required for central leptin signaling to reverse hyperglycemia and dyslipidemia in insulin-deficient mice. Ablation of LEPRs in RIP-Cre 25Mgn neurons completely blocks glucose-lowering effects of leptin in insulin-deficient mice. Further investigations reveal that insulin-deficient mice lacking LEPRs in RIP-Cre 25Mgn neurons (RIP-Cre ΔLEPR mice) exhibit greater lipid levels in blood and liver compared to wild-type controls, and that leptin injection into the brain does not suppress dyslipidemia in insulin-deficient RIP-Cre ΔLEPR mice. Leptin administration into the brain combined with acipimox, which lowers blood lipids by suppressing triglyceride lipase activity, can restore normal glycemia in insulin-deficient RIP-Cre ΔLEPR mice, suggesting that excess circulating lipids are a driving-force of hyperglycemia in insulin-deficient RIP-Cre ΔLEPR mice. Collectively, our data demonstrate that LEPRs in RIP-Cre 25Mgn neurons significantly contribute to glucose-lowering effects of leptin in an insulin-independent manner by suppression of dyslipidemia.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":126404,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"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":0.9427,"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":320544,"name":"Juan Pablo Palavicini","orcid":"0000-0001-9667-8438","position":1,"is_corresponding":false},{"id":232145,"name":"Meixia Pan","orcid":"0000-0001-5697-6086","position":2,"is_corresponding":false},{"id":268338,"name":"Darleen A. Sandoval","orcid":"0000-0003-3669-3278","position":3,"is_corresponding":false},{"id":232153,"name":"Xianlin Han","orcid":"0000-0002-8615-2413","position":4,"is_corresponding":false},{"id":384725,"name":"Teppei Fujikawa","orcid":"0000-0002-4056-0526","position":5,"is_corresponding":false},{"id":384724,"name":"Ashish Kumar Singha","orcid":"0000-0002-4882-9278","position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":{"citation_network_status":"fetched"},"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":[]}