{"doi":"10.1186/s12933-024-02565-9","title":"Evaluating sex-specific responses to western diet across the lifespan: impact on cardiac function and transcriptomic signatures in C57BL/6J mice at 530 and 640/750 days of age","abstract":"BACKGROUND: Long-term consumption of Western Diet (WD) is a well-established risk factor for the development of cardiovascular disease (CVD); however, there is a paucity of studies on the long-term effects of WD on the pathophysiology of CVD and sex-specific responses. METHODS: Our study aimed to investigate the sex-specific pathophysiological changes in left ventricular (LV) function using transthoracic echocardiography (ECHO) and LV tissue transcriptomics in WD-fed C57BL/6 J mice for 125 days, starting at the age of 300 through 425 days. RESULTS: In female mice, consumption of the WD diet showed long-term effects on LV structure and possible development of HFpEF-like phenotype with compensatory cardiac structural changes later in life. In male mice, ECHO revealed the development of an HFrEF-like phenotype later in life without detectable structural alterations. The transcriptomic profile revealed a sex-associated dichotomy in LV structure and function. Specifically, at 530-day, WD-fed male mice exhibited differentially expressed genes (DEGs), which were overrepresented in pathways associated with endocrine function, signal transduction, and cardiomyopathies. At 750 days, WD-fed male mice exhibited dysregulation of several genes involved in various lipid, glucagon, and glutathione metabolic pathways. At 530 days, WD-fed female mice exhibited the most distinctive set of DEGs with an abundance of genes related to circadian rhythms. At 640 days, altered DEGs in WD-fed female mice were associated with cardiac energy metabolism and remodeling. CONCLUSIONS: Our study demonstrated distinct sex-specific and age-associated differences in cardiac structure, function, and transcriptome signature between WD-fed male and female mice.","journal":"Cardiovascular Diabetology","year":2024,"id":439464,"datarank":0.3596842909197557,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"self_citation_contribution":0.3596842909197557,"citation_network_contribution":0.0,"self_endowment_contribution":0.3596842909197557,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9458,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":407635,"name":"Agnieszka Brojakowska","orcid":"0000-0002-7319-9685","position":1,"is_corresponding":false},{"id":1250237,"name":"Roksana Zakharyan","orcid":"0000-0003-3411-7584","position":2,"is_corresponding":false},{"id":1250238,"name":"Siras Hakobyan","orcid":"0000-0002-6875-2482","position":3,"is_corresponding":false},{"id":1250239,"name":"Suren Davitavyan","orcid":"0000-0002-3414-5553","position":4,"is_corresponding":false},{"id":1250798,"name":"Tamara Sirunyan","orcid":null,"position":5,"is_corresponding":false},{"id":1250799,"name":"Gisane Khachatryan","orcid":null,"position":6,"is_corresponding":false},{"id":1250800,"name":"Mary K. Khlgatian","orcid":null,"position":7,"is_corresponding":false},{"id":407634,"name":"Malik Bisserier","orcid":"0000-0001-8826-4649","position":8,"is_corresponding":false},{"id":704853,"name":"Shihong Zhang","orcid":"0000-0002-9661-1089","position":9,"is_corresponding":false},{"id":545863,"name":"Susmita Sahoo","orcid":"0000-0002-7279-1564","position":10,"is_corresponding":false},{"id":407638,"name":"Lahouaria Hadri","orcid":"0000-0001-8108-7993","position":11,"is_corresponding":false},{"id":1250240,"name":"Amit Rai","orcid":"0000-0002-5715-8541","position":12,"is_corresponding":false},{"id":427782,"name":"Venkata Naga Srikanth Garikipati","orcid":"0000-0001-5803-5335","position":13,"is_corresponding":false},{"id":733628,"name":"Arsen Arakelyan","orcid":"0000-0002-6851-1056","position":14,"is_corresponding":false},{"id":407637,"name":"David A. 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