{"doi":"10.1016/j.cdnut.2025.107197","title":"Impact of Weight Cycling on Metabolic Adaptation, GLP-1 Regulation and Epigenetic Modifications","abstract":"Objectives: Current oral pharmacotherapies for obesity might be limited by high hepatic metabolism and low target specificity.Browning subcutaneous white adipose tissue (WAT) is a promising way, as the WAT contains adipose stromal stem cells (ASCs) that can be differentiated into beige adipocytes under appropriate stimuli.Trans-resveratrol (R), a potent browning agent<, has poor solubility, stability, and target specificity.To address this, R was encapsulated in nanoparticles (R-NPs).Conjugating an ASC-targeting peptide (GSWKYWF-GEGGC, ASC-1) on the R-NP surface promoted ASC differentiation into beige adipocytes and reduced obesity when delivered intravenously.However, further studies are needed to assess the potential anti-obesity effects of a truncated peptide (KYWFGEC, ASC-2), with lower cost and higher solubility.Methods: Six-week-old C57BL/6J mice on a high-fat diet were randomly assigned to one of four treatments for five weeks: Control, non-targeted R-NPs, ASC-1-R-NPs, or ASC-2-R-NPs.Treatments (30 mg R/kg body weight/injection) were directly injected biweekly into the left and right inguinal WAT (iWAT) alternately.Body composition was measured weekly via Echo MRI.The glucose tolerance test (GTT) and insulin tolerance tests (ITT) were performed.The browning and lipid metabolismrelated gene expressions were analyzed using RT-qPCR.results: Compared to the Control, R-NPs, ASC-1-R-NPs, and ASC-2-R-NPs treatments decreased fat mass by 15%, 15%, and 23%, and iWAT weight by 12%, 26%, and 38%, respectively.GTT responses were similar across groups, but ITT results showed improved insulin sensitivity in ASC-1-R-NPs and ASC-2-R-NPs groups.In the iWAT, browning-related Tmem26 gene expression increased 3-fold in ASC-1-R-NPs group.Moreover, the Ucp1 increased 1.4 and 2.2-fold in ASC-1-R-NPs-and ASC-2-R-NPs groups, though lacking significance due to small sample size.The lipogenesis-related ACC1 gene expression was 56% lower in ASC-2-R-NPs, and SCD1 was 52% and 70% lower in ASC-1-R-NPs-and ASC-2-R-NPs compared to the Control.Conclusions: ASC-2-R-NPs and ASC-1-R-NPs reduce fat mass and improve insulin tolerance but not glucose tolerance, while ASC-1-R-NPs promote Tmem26 expression and ASC-2-R-NPs suppress ACC1 and SCD1 expression, highlighting their potential for obesity management.","journal":"Current Developments in Nutrition","year":2025,"id":567097,"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":0.9606,"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":482591,"name":"Rong Fan","orcid":"0000-0001-7250-7546","position":1,"is_corresponding":false},{"id":482594,"name":"Soonkyu Chung","orcid":"0000-0001-6279-7017","position":2,"is_corresponding":false},{"id":668786,"name":"Young-Cheul Kim","orcid":null,"position":3,"is_corresponding":false},{"id":482592,"name":"Judy Kim","orcid":"0000-0002-7076-9398","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:56:44.340853Z","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":[]}