{"doi":"10.1016/j.molmet.2023.101751","title":"Pharmacological inhibition of lipolysis prevents adverse metabolic outcomes during glucocorticoid administration","abstract":"OBJECTIVE: Glucocorticoids are one of the most commonly prescribed classes of anti-inflammatory drugs; however, chronic treatment promotes iatrogenic (drug-induced) diabetes. As part of their physiological role, glucocorticoids stimulate lipolysis to spare glucose. We hypothesized that persistent stimulation of lipolysis during glucocorticoid therapy plays a causative role in the development of iatrogenic diabetes. METHODS: Male C57BL/6J mice were given 100 μg/mL corticosterone (Cort) in the drinking water for two weeks and were fed either normal chow (TekLad 8640) or the same diet supplemented with an adipose triglyceride lipase inhibitor (Atglistatin - 2 g/kg diet) to inhibit the first step of lipolysis. RESULTS: Herein, we report for the first time that glucocorticoid administration promotes a unique state of substrate excess and energetic overload in skeletal muscle that primarily results from the rampant mobilization of endogenous fuels. Inhibiting lipolysis protected mice from Cort-induced gains in fat mass, excess ectopic lipid accrual, hyperinsulinemia, and hyperglycemia. The role lipolysis plays in Cort-mediated pathology appears to differ between tissues. Within skeletal muscle, Cort-induced lipolysis facilitated diversion of glucose-derived carbons toward the pentose phosphate and hexosamine biosynthesis pathways but contributed to <3% of the Cort-induced genomic adaptations. In contrast, Cort stimulation of lipolysis accounted for ∼35% of the genomic changes in the liver but had minimal impact on hepatic metabolites reported. CONCLUSIONS: These data support the idea that activation of lipolysis plays a causal role in the progression toward iatrogenic diabetes during glucocorticoid therapy with differential impact on skeletal muscle and liver.","journal":"Molecular Metabolism","year":2023,"id":352664,"datarank":0.32958368660043297,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.0,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9553,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":418292,"name":"Susan J. Burke","orcid":"0000-0003-2571-4416","position":1,"is_corresponding":false},{"id":1098518,"name":"Humza A. Pirzadah","orcid":"0009-0009-6815-1896","position":2,"is_corresponding":false},{"id":1098972,"name":"Tai‐Yu Huang","orcid":null,"position":3,"is_corresponding":false},{"id":419208,"name":"Heidi M. Batdorf","orcid":null,"position":4,"is_corresponding":false},{"id":1098973,"name":"Walid K. Mohammed","orcid":null,"position":5,"is_corresponding":false},{"id":881015,"name":"Katarina A. Jones","orcid":"0000-0003-3769-8599","position":6,"is_corresponding":false},{"id":250669,"name":"Sujoy Ghosh","orcid":"0000-0002-7601-165X","position":7,"is_corresponding":false},{"id":621104,"name":"Shawn R. Campagna","orcid":"0000-0001-6809-3862","position":8,"is_corresponding":false},{"id":418284,"name":"J. Jason Collier","orcid":"0000-0003-2817-4152","position":9,"is_corresponding":false},{"id":289078,"name":"Robert C. Noland","orcid":"0000-0001-5543-3450","position":10,"is_corresponding":false},{"id":473002,"name":"Melissa A. Linden","orcid":"0000-0002-3152-0864","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:12:54.209378Z","pmid":"37295745","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":[]}