{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Nguyen PTT"],"funding":["National Institute of Arthritis and Musculoskeletal and Skin Diseases","National Institute of Environmental Health Sciences","National Institutes of Health National Cancer Institute","Ludwig Institute for Cancer Research Ltd","NIDDK NIH HHS","National Institute of Diabetes and Digestive and Kidney Diseases","Blavatnik Family Foundation","NCI NIH HHS","National Institutes of Health","NIAMS NIH HHS","NIH HHS"],"pagination":["115284"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12010789"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["44(2)"],"pubmed_abstract":["ATP-citrate lyase (ACLY) generates cytosolic acetyl-coenzyme A (acetyl-CoA) for lipid synthesis and is a promising therapeutic target in diseases with altered lipid metabolism. Here, we developed inducible whole-body Acly-knockout mice to determine the requirement for ACLY in normal tissue functions, uncovering its crucial role in skin homeostasis. ACLY-deficient skin upregulates the acetyl-CoA synthetase ACSS2; deletion of both Acly and Acss2 from the skin exacerbates skin abnormalities, with differential effects on two major lipid-producing skin compartments. While the epidermis is depleted of barrier lipids, the sebaceous glands increase production of sebum, supplied at least in part by circulating fatty acids and coinciding with adipose lipolysis and fat depletion. Dietary fat suppleme"],"journal":["Cell reports"],"pubmed_title":["Acetyl-CoA synthesis in the skin is a key determinant of systemic lipid homeostasis."],"pmcid":["PMC12010789"],"funding_grant_id":["F31 AR079845","R01 AR082256","R01 DK116005","T32 CA115299","R01 CA262055","S10 OD025098","T32 AR007465","P30 AR069589","F30 DK126353","R01 AR077615","K00 CA245802","K00 CA212455","T32 DK007314"],"pubmed_authors":["Kuprasertkul N","Izzo LT","Pinheiro LV","Costa-Pinheiro P","Seykora JT","Wellen KE","Shiue M","Harris JC","Mesaros C","Nguyen PTT","Affronti HA","Ghaisas S","Yang X","Kambayashi T","Gugiu G","Liu JY","Bradley CW","Capell BC"],"additional_accession":[]},"is_claimable":false,"name":"Acetyl-CoA synthesis in the skin is a key determinant of systemic lipid homeostasis.","description":"ATP-citrate lyase (ACLY) generates cytosolic acetyl-coenzyme A (acetyl-CoA) for lipid synthesis and is a promising therapeutic target in diseases with altered lipid metabolism. Here, we developed inducible whole-body Acly-knockout mice to determine the requirement for ACLY in normal tissue functions, uncovering its crucial role in skin homeostasis. ACLY-deficient skin upregulates the acetyl-CoA synthetase ACSS2; deletion of both Acly and Acss2 from the skin exacerbates skin abnormalities, with differential effects on two major lipid-producing skin compartments. While the epidermis is depleted of barrier lipids, the sebaceous glands increase production of sebum, supplied at least in part by circulating fatty acids and coinciding with adipose lipolysis and fat depletion. Dietary fat suppleme","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Feb","modification":"2026-06-03T04:52:23.798Z","creation":"2025-07-03T03:05:23.698Z"},"accession":"S-EPMC12010789","cross_references":{"pubmed":["39932848"],"doi":["10.1016/j.celrep.2025.115284"]}}