{"doi":"10.1096/fj.201901900r","title":"Activation of AMP‐activated protein kinase during sepsis/inflammation improves survival by preserving cellular metabolic fitness","abstract":"Abstract The purpose was to determine the role of AMPK activation in the renal metabolic response to sepsis, the development of sepsis‐induced acute kidney injury (AKI) and on survival. In a prospective experimental study, 167 10‐ to 12‐week‐old C57BL/6 mice underwent cecal ligation and puncture (CLP) and human proximal tubule epithelial cells (TEC; HK2) were exposed to inflammatory mix (IM), a combination of lipopolysaccharide (LPS) and high mobility group box 1 (HMGB1). Renal/TEC metabolic fitness was assessed by monitoring the expression of drivers of oxidative phosphorylation (OXPHOS), the rates of utilization of OXPHOS/glycolysis in response to metabolic stress, and mitochondrial function by measuring O 2 consumption rates (OCR) and the membrane potential (Δψ m ). Sepsis/IM resulted in AKI, increased mortality, and in renal AMPK activation 6‐24 hours after CLP/IM. Pharmacologic activation of AMPK with 5‐aminoimidazole‐4‐carboxamide ribonucleotide (AICAR) or metformin during sepsis improved the survival, while AMPK inhibition with Compound C increased mortality, impaired mitochondrial respiration, decreased OCR, and disrupted TEC metabolic fitness. AMPK‐driven protection was associated with increased Sirt 3 expression and restoration of metabolic fitness. Renal AMPK activation in response to sepsis/IM is an adaptive mechanism that protects TEC, organs, and the host by preserving mitochondrial function and metabolic fitness likely through Sirt3 signaling.","journal":"The FASEB Journal","year":2020,"id":57597,"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":77,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9654,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":301206,"name":"Yujie Ma","orcid":"0000-0002-2386-1482","position":1,"is_corresponding":false},{"id":303149,"name":"Carlos L. Manrique‐Caballero","orcid":null,"position":2,"is_corresponding":false},{"id":301207,"name":"Hui Li","orcid":"0000-0003-1942-2441","position":3,"is_corresponding":false},{"id":301208,"name":"David R. Emlet","orcid":"0000-0003-2131-9902","position":4,"is_corresponding":false},{"id":301209,"name":"Shengnan Li","orcid":"0000-0002-0257-4708","position":5,"is_corresponding":false},{"id":301210,"name":"Catherine J. Baty","orcid":"0000-0002-9504-9979","position":6,"is_corresponding":false},{"id":301211,"name":"Xiao‐Yan Wen","orcid":"0000-0001-6728-0025","position":7,"is_corresponding":false},{"id":301212,"name":"Nahmah Kim‐Campbell","orcid":"0000-0002-5826-0388","position":8,"is_corresponding":false},{"id":303150,"name":"A. Frank","orcid":null,"position":9,"is_corresponding":false},{"id":303151,"name":"Elizabeth V. Menchikova","orcid":null,"position":10,"is_corresponding":false},{"id":301213,"name":"Núria M. Pastor‐Soler","orcid":"0000-0001-5807-6620","position":11,"is_corresponding":false},{"id":247713,"name":"Kenneth R. Hallows","orcid":"0000-0002-2964-2440","position":12,"is_corresponding":false},{"id":264558,"name":"Edwin K. Jackson","orcid":"0000-0002-8101-6009","position":13,"is_corresponding":false},{"id":106180,"name":"Sruti Shiva","orcid":"0000-0003-3535-2113","position":14,"is_corresponding":false},{"id":34787,"name":"Michael R. Pinsky","orcid":"0000-0001-6166-700X","position":15,"is_corresponding":false},{"id":280759,"name":"Brian S. Zuckerbraun","orcid":"0000-0002-5226-1857","position":16,"is_corresponding":false},{"id":108959,"name":"John A. Kellum","orcid":"0000-0003-1995-2653","position":17,"is_corresponding":false},{"id":301214,"name":"Hernando Gómez","orcid":"0000-0001-5605-3513","position":18,"is_corresponding":false},{"id":301205,"name":"Kui Jin","orcid":"0000-0002-2272-9949","position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-18T21:06:48.611399Z","pmid":"32246808","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":[]}