{"doi":"10.3389/fnut.2025.1665682","title":"Long-term dietary restriction changes lipid homeostasis and consequently impairs testosterone production in aged Wistar rats","abstract":"Testosterone (T) is a central androgen responsible for the maintenance of vegetative and reproductive functions and sexual behavior in males. T is mainly synthesized through the process of testicular steroidogenesis with cholesterol (CHOL) as the initial precursor. It is known that T levels gradually decrease, along with an increase in CHOL, LDL-C, triglycerides (TG), and a decrease in HDL-C in advanced stages of life. Dietary restriction (DR) ameliorates lipid status and raises T levels in obese and overweight men. Here, we investigated whether the beneficial effects of DR on serum lipid status consequently improve T production at advanced stages; therefore, we exposed male Wistar rats to long-term DR (LTDR, 18 months). We confirmed an age-related decrease in serum T levels, reduced expression of genes and proteins of steroidogenic machinery with a simultaneous increase in serum CHOL, LDL-C, and TG levels. LTDR additionally decreased T synthesis, expression of Star /StAR and Cyp11a1 /CYP11A1, and testicular CHOL levels. At the same time, LTDR reduced serum CHOL, LDL-C, and TG levels and increased HDL-C levels. To confirm that the effects of DR are determined by the duration of the treatment, we also checked the effects of the short-term DR (STDR, 3 months) and demonstrated that STDR did not alter T levels and did not affect serum lipids. Our results indicate the importance of sustained systemic lipid homeostasis for T production in advanced life stages and show that the effects of restricted food intake on testicular androgen capacity depend on the duration of DR.","journal":"Frontiers in Nutrition","year":2025,"id":536701,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.957,"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":498799,"name":"Milica Prvulović","orcid":"0000-0003-2769-5212","position":1,"is_corresponding":false},{"id":1422022,"name":"Valentina Simeunovic","orcid":"0000-0002-3042-0810","position":2,"is_corresponding":false},{"id":498796,"name":"Smilja Todorović","orcid":"0000-0001-7155-4914","position":3,"is_corresponding":false},{"id":498793,"name":"Aleksandra Mladenović","orcid":"0000-0001-9011-5634","position":4,"is_corresponding":false},{"id":737570,"name":"Srdjan J. Sokanovic","orcid":"0000-0002-5368-5897","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-19T02:52:09.056872Z","pmid":"41049368","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":[]}