{"doi":"10.2337/db09-0929","title":"Leucine Deprivation Decreases Fat Mass by Stimulation of Lipolysis in White Adipose Tissue and Upregulation of Uncoupling Protein 1 (UCP1) in Brown Adipose Tissue","abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE</jats:title>\n                  <jats:p>White adipose tissue (WAT) and brown adipose tissue (BAT) play distinct roles in adaptation to changes in nutrient availability, with WAT serving as an energy store and BAT regulating thermogenesis. We previously showed that mice maintained on a leucine-deficient diet unexpectedly experienced a dramatic reduction in abdominal fat mass. The cellular mechanisms responsible for this loss, however, are unclear. The goal of current study is to investigate possible mechanisms.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS</jats:title>\n                  <jats:p>Male C57BL/6J mice were fed either control, leucine-deficient, or pair-fed diets for 7 days. Changes in metabolic parameters and expression of genes and proteins related to lipid metabolism were analyzed in WAT and BAT.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS</jats:title>\n                  <jats:p>We found that leucine deprivation for 7 days increases oxygen consumption, suggesting increased energy expenditure. We also observed increases in lipolysis and expression of β-oxidation genes and decreases in expression of lipogenic genes and activity of fatty acid synthase in WAT, consistent with increased use and decreased synthesis of fatty acids, respectively. Furthermore, we observed that leucine deprivation increases expression of uncoupling protein (UCP)-1 in BAT, suggesting increased thermogenesis.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS</jats:title>\n                  <jats:p>We show for the first time that elimination of dietary leucine produces significant metabolic changes in WAT and BAT. The effect of leucine deprivation on UCP1 expression is a novel and unexpected observation and suggests that the observed increase in energy expenditure may reflect an increase in thermogenesis in BAT. Further investigation will be required to determine the relative contribution of UCP1 upregulation and thermogenesis in BAT to leucine deprivation-stimulated fat loss.</jats:p>\n               </jats:sec>","journal":"Diabetes","year":2010,"id":46459,"datarank":6.483611031966829,"base_score":5.1298987149230735,"endowment":5.1298987149230735,"self_citation_contribution":0.7694848072384611,"citation_network_contribution":5.714126224728368,"self_endowment_contribution":0.7694848072384611,"citer_contribution":5.714126224728368,"corpus_percentile":null,"corpus_rank":null,"citation_count":168,"citer_count":152,"citers_with_citation_signal":131,"citers_with_endowment":131,"datacite_reuse_total":2,"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":215468,"name":"Qingshu Meng","orcid":null,"position":1,"is_corresponding":false},{"id":215469,"name":"Chunxia Wang","orcid":null,"position":2,"is_corresponding":false},{"id":215470,"name":"Houkai Li","orcid":null,"position":3,"is_corresponding":false},{"id":215471,"name":"Zhiying Huang","orcid":null,"position":4,"is_corresponding":false},{"id":215472,"name":"Shanghai Chen","orcid":null,"position":5,"is_corresponding":false},{"id":215473,"name":"Fei Xiao","orcid":null,"position":6,"is_corresponding":false},{"id":215474,"name":"Feifan Guo","orcid":null,"position":7,"is_corresponding":false},{"id":44743,"name":"Ying Cheng","orcid":"0000-0001-6125-0677","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Leucine Deprivation Decreases Fat Mass by Stimulation of Lipolysis in White Adipose Tissue and Upregulation of Uncoupling Protein 1 (UCP1) in Brown Adipose Tissue","abstract":"OBJECTIVE: White adipose tissue (WAT) and brown adipose tissue (BAT) play distinct roles in adaptation to changes in nutrient availability, with WAT serving as an energy store and BAT regulating thermogenesis. We previously showed that mice maintained on a leucine-deficient diet unexpectedly experienced a dramatic reduction in abdominal fat mass. The cellular mechanisms responsible for this loss, however, are unclear. The goal of current study is to investigate possible mechanisms. RESEARCH DESIGN AND METHODS: Male C57BL/6J mice were fed either control, leucine-deficient, or pair-fed diets for 7 days. Changes in metabolic parameters and expression of genes and proteins related to lipid metabolism were analyzed in WAT and BAT. RESULTS: We found that leucine deprivation for 7 days increases oxygen consumption, suggesting increased energy expenditure. We also observed increases in lipolysis and expression of beta-oxidation genes and decreases in expression of lipogenic genes and activity of fatty acid synthase in WAT, consistent with increased use and decreased synthesis of fatty acids, respectively. Furthermore, we observed that leucine deprivation increases expression of uncoupling protein (UCP)-1 in BAT, suggesting increased thermogenesis. CONCLUSIONS: We show for the first time that elimination of dietary leucine produces significant metabolic changes in WAT and BAT. The effect of leucine deprivation on UCP1 expression is a novel and unexpected observation and suggests that the observed increase in energy expenditure may reflect an increase in thermogenesis in BAT. Further investigation will be required to determine the relative contribution of UCP1 upregulation and thermogenesis in BAT to leucine deprivation-stimulated fat loss.","is_dataset_classified":null,"base_score":5.1298987149230735,"endowment":5.1298987149230735,"datacite_reuse_total":2,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19833890","pmcid":"PMC2797918","openalex_id":"https://openalex.org/W2167431561","authors":[],"funders":[],"total_grants":0,"fwci":4.4647,"citation_percentile":0.94785003,"influential_citations":12,"citation_trend":[{"year":2012,"count":15},{"year":2013,"count":6},{"year":2014,"count":14},{"year":2015,"count":8},{"year":2016,"count":12},{"year":2017,"count":15},{"year":2018,"count":14},{"year":2019,"count":6},{"year":2020,"count":9},{"year":2021,"count":18},{"year":2022,"count":8},{"year":2023,"count":10},{"year":2024,"count":6},{"year":2025,"count":11},{"year":2026,"count":6}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://diabetesjournals.org/diabetes/article-pdf/59/1/17/664260/zdb00110000017.pdf","host_type":"journal"},{"url":"https://diabetesjournals.org/diabetes/article-pdf/59/1/17/664260/zdb00110000017.pdf","host_type":"HYBRID"},{"url":"https://diabetesjournals.org/diabetes/article-pdf/59/1/17/664260/zdb00110000017.pdf","host_type":"publisher"},{"url":"https://doi.org/10.2337/db09-0929","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/19833890","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2797918","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC2797918","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC2797918?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Adipose Tissue and Metabolism","Adipokines, Inflammation, and Metabolic Diseases","Muscle metabolism and nutrition","Biology","Medicine","Adipose Tissue","Adipose Tissue, Brown","Animals","Calorimetry, Indirect","DNA","Epinephrine","Fatty Acid Synthases","Fatty Acids, Nonesterified","Glucocorticoids","Glycerol","Ion Channels","Leucine","Lipolysis","Male","Mice","Mice, Inbred C57BL","Mitochondrial Proteins","Oxygen Consumption","RNA","Reverse Transcriptase Polymerase Chain Reaction","Uncoupling Protein 1","Up-Regulation"],"mesh_terms":["Uncoupling Protein 1","Adipose Tissue","Animals","Adipose Tissue, Brown","Calorimetry, Indirect","DNA","Epinephrine","Fatty Acids, Nonesterified","Glucocorticoids","Glycerol","Ion Channels","Leucine","Lipolysis","Male","Mice, Inbred C57BL","Oxygen Consumption","RNA","Up-Regulation","Reverse Transcriptase Polymerase Chain Reaction","Mitochondrial Proteins","Mice","Fatty Acid Synthases"],"keywords":["Thermogenesis","Brown adipose tissue","Thermogenin","Endocrinology","Internal medicine","Lipolysis","White adipose tissue","Uncoupling protein","Adipose tissue","Biology","Leucine","Downregulation and upregulation","Chemistry","Biochemistry","Amino acid","Gene","Medicine"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Affordable and clean energy"}],"linked_datasets":[{"doi":"10.6084/m9.figshare.14329367","title":"Additional file 1 of A fifty percent leucine-restricted diet reduces fat mass and improves glucose regulation","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14329367.v1","title":"Additional file 1 of A fifty percent leucine-restricted diet reduces fat mass and improves glucose regulation","publisher":"figshare","resource_type":"JournalArticle"}],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-10T02:49:34.083383Z","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":[]}