{"doi":"10.1172/jci.insight.149271","title":"Placental mTOR complex 1 regulates fetal programming of obesity and insulin resistance in mice","abstract":"Fetal growth restriction, or low birth weight, is a strong determinant for eventual obesity and type 2 diabetes. Clinical studies suggest placental mechanistic target of rapamycin (mTOR) signaling regulates fetal birth weight and the metabolic health trajectory of the offspring. In the current study, we used a genetic model with loss of placental mTOR function (mTOR-KOPlacenta) to test the direct role of mTOR signaling on birth weight and metabolic health in the adult offspring. mTOR-KOPlacenta animals displayed reduced placental area and total weight, as well as fetal body weight at embryonic day (E) 17.5. Birth weight and serum insulin levels were reduced; however, β cell mass was normal in mTOR-KOPlacenta newborns. Adult mTOR-KOPlacenta offspring, under a metabolic high-fat challenge, displayed exacerbated obesity and metabolic dysfunction compared with littermate controls. Subsequently, we tested whether enhancing placental mTOR complex 1 (mTORC1) signaling, via genetic ablation of TSC2, in utero would improve glucose homeostasis in the offspring. Indeed, increased placental mTORC1 conferred protection from diet-induced obesity in the offspring. In conclusion, placental mTORC1 serves as a mechanistic link between placental function and programming of obesity and insulin resistance in the adult offspring.","journal":"JCI Insight","year":2021,"id":164943,"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":37,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9521,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":493696,"name":"Daniel Baumann","orcid":"0000-0003-3669-2064","position":1,"is_corresponding":false},{"id":687600,"name":"Megan Beetch","orcid":"0000-0003-4338-4350","position":2,"is_corresponding":false},{"id":480686,"name":"Amber Lockridge","orcid":"0000-0003-1122-6286","position":3,"is_corresponding":false},{"id":383332,"name":"Seokwon Jo","orcid":"0000-0002-8989-4893","position":4,"is_corresponding":false},{"id":493697,"name":"Alicia Wong","orcid":"0000-0002-1018-3539","position":5,"is_corresponding":false},{"id":688502,"name":"Tate Zemanovic","orcid":null,"position":6,"is_corresponding":false},{"id":480687,"name":"Ramkumar Mohan","orcid":"0000-0002-1308-1642","position":7,"is_corresponding":false},{"id":687601,"name":"Danica L. Fondevilla","orcid":"0000-0003-0706-9521","position":8,"is_corresponding":false},{"id":500598,"name":"Michelle Sia","orcid":"0000-0001-9353-3356","position":9,"is_corresponding":false},{"id":232440,"name":"Maria Ruth Pineda-Cortel","orcid":"0000-0001-6157-7012","position":10,"is_corresponding":false},{"id":232435,"name":"Emilyn U. Alejandro","orcid":"0000-0002-7941-8439","position":11,"is_corresponding":false},{"id":464947,"name":"Brian Akhaphong","orcid":"0000-0002-1268-6623","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-18T23:45:36.425208Z","pmid":"34032632","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":[]}