{"doi":"10.1371/journal.pone.0079841","title":"Keap1-Knockdown Decreases Fasting-Induced Fatty Liver via Altered Lipid Metabolism and Decreased Fatty Acid Mobilization from Adipose Tissue","abstract":null,"journal":"PLoS ONE","year":2013,"id":593010,"datarank":2.53588057991218,"base_score":4.04305126783455,"endowment":4.04305126783455,"self_citation_contribution":0.6064576901751826,"citation_network_contribution":1.9294228897369978,"self_endowment_contribution":0.6064576901751826,"citer_contribution":1.9294228897369978,"corpus_percentile":null,"corpus_rank":null,"citation_count":56,"citer_count":54,"citers_with_citation_signal":51,"citers_with_endowment":51,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":535475,"name":"Ajay C. Donepudi","orcid":"0000-0001-7940-4451","position":1,"is_corresponding":false},{"id":1517618,"name":"Jamie E. Moscovitz","orcid":null,"position":2,"is_corresponding":false},{"id":324997,"name":"Angela L. Slitt","orcid":null,"position":3,"is_corresponding":false},{"id":476518,"name":"Jialin Xu","orcid":"0000-0002-3910-1306","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Keap1-Knockdown Decreases Fasting-Induced Fatty Liver via Altered Lipid Metabolism and Decreased Fatty Acid Mobilization from Adipose Tissue","abstract":"AIMS: The purpose of this study was to determine whether Nrf2 activation, via Keap1-knockdown (Keap1-KD), regulates lipid metabolism and mobilization induced by food deprivation (e.g. fasting). METHODS AND RESULTS: Male C57BL/6 (WT) and Keap1-KD mice were either fed ad libitum or food deprived for 24 hours. After fasting, WT mice exhibited a marked increase in hepatic lipid accumulation, but Keap1-KD mice had an attenuated increase of lipid accumulation, along with reduced expression of lipogenic genes (acetyl-coA carboxylase, stearoyl-CoA desaturase-1, and fatty acid synthase) and reduced expression of genes related to fatty acid transport, such as fatty acid translocase/CD36 (CD36) and Fatty acid transport protein (FATP) 2, which may attribute to the reduced induction of Peroxisome proliferator-activated receptor (Ppar) α signaling in the liver. Additionally, enhanced Nrf2 activity by Keap1-KD increased AMP-activated protein kinase (AMPK) phosphorylation in liver. In white adipose tissue, enhanced Nrf2 activity did not change the lipolysis rate by fasting, but reduced expression of fatty acid transporters--CD36 and FATP1, via a PPARα-dependent mechanism, which impaired fatty acid transport from white adipose tissue to periphery circulation system, and resulted in increased white adipose tissue fatty acid content. Moreover, enhanced Nrf2 activity increased glucose tolerance and Akt phosphorylation levels upon insulin administration, suggesting Nrf2 signaling pathway plays a key role in regulating insulin signaling and enhanced insulin sensitivity in skeletal muscle. CONCLUSION: Enhanced Nrf2 activity via Keap1-KD decreased fasting-induced steatosis, pointing to an important function of Nrf2 on lipid metabolism under the condition of nutrient deprivation.","is_dataset_classified":null,"base_score":4.04305126783455,"endowment":4.04305126783455,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"24224011","pmcid":"PMC3817107","openalex_id":"https://openalex.org/W2042074675","authors":[],"funders":[{"funder_name":"NIEHS NIH HHS","grant_id":"3R01ES016042-2S2","title":null},{"funder_name":"NIEHS NIH HHS","grant_id":"K22 ES013782","title":null},{"funder_name":"NIEHS NIH HHS","grant_id":"R01 ES016042","title":null},{"funder_name":"NIEHS NIH HHS","grant_id":"5R01ES016042-04","title":"Effect of nutritional status on MRP2 expression and biliary excretion of bispheno"},{"funder_name":"NCRR NIH HHS","grant_id":"P20 RR016457","title":null},{"funder_name":"NCRR NIH HHS","grant_id":"5P20RR016457-11","title":"INTERNET-BASED ADDICTION COUNSELOR EDUCATION STUDY"},{"funder_name":"NIEHS NIH HHS","grant_id":"5K22ES013782-03","title":"Role of Nrf2 during cholestsis and gallstone formation"},{"funder_name":"NIGMS NIH HHS","grant_id":"P20 GM103430","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"8P20GM103430-11","title":null},{"funder_name":"National Institutes of Health","grant_id":"2P20GM103430-14","title":"Bioinformatics Core"}],"total_grants":10,"fwci":2.4764,"citation_percentile":0.89401316,"influential_citations":0,"citation_trend":[{"year":2014,"count":2},{"year":2015,"count":11},{"year":2016,"count":5},{"year":2017,"count":4},{"year":2018,"count":6},{"year":2019,"count":4},{"year":2020,"count":3},{"year":2021,"count":5},{"year":2022,"count":3},{"year":2023,"count":4},{"year":2024,"count":5},{"year":2025,"count":4}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0079841&type=printable","host_type":"journal"},{"url":"https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0079841&type=printable","host_type":"publisher"},{"url":"http://dx.plos.org/10.1371/journal.pone.0079841","host_type":"publisher"},{"url":"https://doi.org/10.1371/journal.pone.0079841","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/24224011","host_type":"repository"},{"url":"https://digitalcommons.uri.edu/bps_facpubs/24","host_type":"journal"},{"url":"http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.793.567","host_type":""},{"url":"http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.853.9678","host_type":""},{"url":"https://doaj.org/article/10f553a2fe6145878879302b9e7a16ab","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3817107","host_type":"repository"},{"url":"https://figshare.com/articles/dataset/_Keap1_Knockdown_Decreases_Fasting_Induced_Fatty_Liver_via_Altered_Lipid_Metabolism_and_Decreased_Fatty_Acid_Mobilization_from_Adipose_Tissue_/840781","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC3817107","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC3817107?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1371/journal.pone.0079841","host_type":""},{"url":"https://dx.doi.org/10.1371/journal.pone.0079841","host_type":""},{"url":"https://doi.org/https://doi.org/10.1371/journal.pone.0079841","host_type":""}],"fields_of_study":["Genomics, phytochemicals, and oxidative stress","Liver Disease Diagnosis and Treatment","Adipose Tissue and Metabolism","0301 basic medicine","0303 health sciences","03 medical and health sciences","Adaptor Proteins, Signal Transducing","Adipose Tissue","Animals","Cytoskeletal Proteins","Fasting","Fatty Acids","Fatty Liver","Kelch-Like ECH-Associated Protein 1","Lipid Metabolism","Male","Mice","Mice, Inbred C57BL"],"mesh_terms":["Kelch-Like ECH-Associated Protein 1","Adipose Tissue","Animals","Cytoskeletal Proteins","Fasting","Fatty Acids","Fatty Liver","Male","Mice, Inbred C57BL","Adaptor Proteins, Signal Transducing","Lipid Metabolism","Mice"],"keywords":["CD36","Endocrinology","Internal medicine","Fatty acid synthase","Fatty acid","Lipid metabolism","White adipose tissue","Biology","adipocyte protein 2","Adipose tissue","Fatty liver","Lipogenesis","Beta oxidation","Fatty acid metabolism","Chemistry","Biochemistry","Metabolism","Receptor","Medicine","Male","Kelch-Like ECH-Associated Protein 1","Science","Q","Fatty Acids","R","610","Fasting","Mice, Inbred C57BL","Cytoskeletal Proteins","Mice","Animals","Research Article","Adaptor Proteins, Signal Transducing"],"sdg_mappings":[{"sdg_number":2,"sdg_label":"2. 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