{"doi":"10.29011/2575-7083.100281","title":"The Adipocyte Na/K-Atpase Oxidant Amplification Loop is the Central Regulator of Western Diet-Induced Obesity and Associated Comorbidities","abstract":"Obesity has become a worldwide epidemic.We have previously reported that systemic administration of pNaKtide which targets the Na/K-ATPase oxidant amplification loop (NKAL) was able to decrease systemic oxidative stress in mice.As adipocytes are believed to play a central role in the development of oxidative stress and its related comorbidities, we examined whether lentiviralmediated adipocyte-specific expression of NaKtide, a peptide derived from the N domain of the Na/K-ATPase 1 subunit, could ameliorate the effects of the WD.C57BL/6 mice were fed a WD, which activated Na/K-ATPase signaling in the adipocytes and induced an obese phenotype, causing increases in plasma levels of leptin, IL-6, and TNF.WD also showed decreased locomotor activity and downregulated tyrosine hydroxylase in brain tissue, but increased markers of neurodegeneration and neuronal apoptosis.Lentiviral-mediated adipocyte-specific expression of NaKtide in mice fed a WD attenuated all these changes including the brain biochemical alterations and behavioral adaptations.These data suggest that adipocyte-derived cytokines play an essential role in the development of obesity induced by a WD and that targeting the adipocyte NKAL loop may serve as an effective therapeutic strategy.","journal":"Cardiology Research and Cardiovascular Medicine","year":2025,"id":564160,"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":0.9599,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1467586,"name":"Cameron Brickman","orcid":null,"position":1,"is_corresponding":false},{"id":410592,"name":"Athar Nawab","orcid":null,"position":2,"is_corresponding":false},{"id":1467587,"name":"Cameron Cottrill","orcid":null,"position":3,"is_corresponding":false},{"id":410594,"name":"Brian Snoad","orcid":null,"position":4,"is_corresponding":false},{"id":409518,"name":"Hari Vishal Lakhani","orcid":"0000-0002-5308-2164","position":5,"is_corresponding":false},{"id":22774,"name":"Juan R Sanabria","orcid":null,"position":6,"is_corresponding":false},{"id":408136,"name":"Zijian Xie","orcid":null,"position":7,"is_corresponding":false},{"id":1467588,"name":"Joseph I Shapiro","orcid":null,"position":8,"is_corresponding":false},{"id":409515,"name":"Komal Sodhi","orcid":"0000-0002-1179-2985","position":9,"is_corresponding":false},{"id":409519,"name":"Jiang Liu","orcid":"0000-0002-0654-707X","position":10,"is_corresponding":false},{"id":1467585,"name":"Rebecca D Pratt","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:56:20.933088Z","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":[]}