{"doi":"10.1101/2024.08.06.606880","title":"Cysteine depletion triggers adipose tissue thermogenesis and weight-loss","abstract":"Abstract Dietary interventions such as caloric restriction (CR) 1 and methionine restriction 2 that prolong lifespan induce the ‘browning’ of white adipose tissue (WAT), an adaptive metabolic response that increases heat production to maintain health 3,4 . However, how diet influences adipose browning and metabolic health is unclear. Here, we identified that weight-loss induced by CR in humans 5 reduces cysteine concentration in WAT suggesting depletion of this amino-acid may be involved in metabolic benefits of CR. To investigate the role of cysteine on organismal metabolism, we created a cysteine-deficiency mouse model in which dietary cysteine was eliminated and cystathionine γ-lyase (CTH) 6 , the enzyme that synthesizes cysteine was conditionally deleted. Using this animal model, we found that systemic cysteine-depletion causes drastic weight-loss with increased fat utilization and browning of adipose tissue. The restoration of dietary cysteine in cysteine-deficient mice rescued weight loss together with reversal of adipose browning and increased food-intake in an on-demand fashion. Mechanistically, cysteine deficiency induced browning and weight loss is dependent on sympathetic nervous system derived noradrenaline signaling via β3-adrenergic-receptors and does not require UCP1. Therapeutically, in high-fat diet fed obese mice, one week of cysteine-deficiency caused 30% weight-loss and reversed inflammation. These findings thus establish that cysteine is essential for organismal metabolism as removal of cysteine in the host triggers adipose browning and rapid weight loss.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":487252,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9543,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":892034,"name":"Lucie Orliaguet","orcid":"0000-0002-3209-457X","position":1,"is_corresponding":false},{"id":556361,"name":"Yun‐Hee Youm","orcid":"0000-0002-8098-8527","position":2,"is_corresponding":false},{"id":1188908,"name":"Rae Maeda","orcid":null,"position":3,"is_corresponding":false},{"id":556872,"name":"Tamara Dlugos","orcid":null,"position":4,"is_corresponding":false},{"id":571199,"name":"Yuanjiu Lei","orcid":"0000-0002-7486-4261","position":5,"is_corresponding":false},{"id":445317,"name":"Daniel Coman","orcid":"0000-0002-6289-0817","position":6,"is_corresponding":false},{"id":280215,"name":"Irina Shchukina","orcid":null,"position":7,"is_corresponding":false},{"id":1331579,"name":"Sairam Andhey","orcid":null,"position":8,"is_corresponding":false},{"id":300728,"name":"Steven R. Smith","orcid":"0000-0002-5098-8147","position":9,"is_corresponding":false},{"id":235348,"name":"Éric Ravussin","orcid":"0000-0003-2129-547X","position":10,"is_corresponding":false},{"id":289082,"name":"Krisztián Stadler","orcid":"0000-0003-3187-5793","position":11,"is_corresponding":false},{"id":445316,"name":"Fahmeed Hyder","orcid":"0000-0001-7822-4002","position":12,"is_corresponding":false},{"id":52958,"name":"Maxim N. Artyomov","orcid":"0000-0002-1133-4212","position":13,"is_corresponding":false},{"id":112019,"name":"Yuki Sugiura","orcid":"0000-0002-6983-8958","position":14,"is_corresponding":false},{"id":269782,"name":"Vishwa Deep Dixit","orcid":"0000-0002-5341-6494","position":15,"is_corresponding":false},{"id":272573,"name":"Aileen H. Lee","orcid":null,"position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-19T02:08:06.013846Z","pmid":"39149397","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":[]}