{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Gomes KP"],"funding":["Univeristy Hospital Foundation"],"pagination":["2384-2408"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12423331"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["17(9)"],"pubmed_abstract":["Lymphedema is a chronic lymphatic disorder characterized by persistent tissue swelling, pain, and recurrent infections, often secondary to cancer treatment, surgery, or obesity. Obesity-associated increases in saturated fatty acids (SFAs) have been linked to lipotoxicity. In this study, patients with secondary lymphedema showed a significantly lower plasma polyunsaturated to saturated fatty acid (PUFA/SFA) ratio compared to BMI-matched controls. Stearic acid, a common dietary SFA, induced apoptosis, oxidative stress, and endoplasmic reticulum (ER) stress in human lymphatic endothelial cells. In a mouse model, a short-term high-SFA diet was used to lower the plasma PUFA/SFA ratio, which worsened tail swelling, oxidative stress, ER stress, and tissue damage following lymphatic injury. Switching to a standard chow diet after surgery prevented these effects. Patients with lymphedema also exhibited elevated levels of fatty acid-binding protein 4 (FABP4), a lipid chaperone associated with metabolic stress. FABP4 inhibition reduced stearic acid-induced cell death in vitro and mitigated tissue damage in vivo. These findings suggest a pathogenic role for SFAs and support dietary modulation and FABP4 inhibition as potential therapeutic strategies for lymphedema."],"journal":["EMBO molecular medicine"],"pubmed_title":["Saturated fatty acids induce lipotoxicity in lymphatic endothelial cells contributing to secondary lymphedema development."],"pmcid":["PMC12423331"],"funding_grant_id":["RES0056514"],"pubmed_authors":["Yang X","Munhoz J","Patel N","Goruk S","Field CJ","Gomes KP","Gibson SB","Korodimas J","Liu E"],"additional_accession":[]},"is_claimable":false,"name":"Saturated fatty acids induce lipotoxicity in lymphatic endothelial cells contributing to secondary lymphedema development.","description":"Lymphedema is a chronic lymphatic disorder characterized by persistent tissue swelling, pain, and recurrent infections, often secondary to cancer treatment, surgery, or obesity. Obesity-associated increases in saturated fatty acids (SFAs) have been linked to lipotoxicity. In this study, patients with secondary lymphedema showed a significantly lower plasma polyunsaturated to saturated fatty acid (PUFA/SFA) ratio compared to BMI-matched controls. Stearic acid, a common dietary SFA, induced apoptosis, oxidative stress, and endoplasmic reticulum (ER) stress in human lymphatic endothelial cells. In a mouse model, a short-term high-SFA diet was used to lower the plasma PUFA/SFA ratio, which worsened tail swelling, oxidative stress, ER stress, and tissue damage following lymphatic injury. Switching to a standard chow diet after surgery prevented these effects. Patients with lymphedema also exhibited elevated levels of fatty acid-binding protein 4 (FABP4), a lipid chaperone associated with metabolic stress. FABP4 inhibition reduced stearic acid-induced cell death in vitro and mitigated tissue damage in vivo. These findings suggest a pathogenic role for SFAs and support dietary modulation and FABP4 inhibition as potential therapeutic strategies for lymphedema.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Sep","modification":"2026-06-03T02:27:51.595Z","creation":"2026-04-23T03:10:30.942Z"},"accession":"S-EPMC12423331","cross_references":{"pubmed":["40759794"],"doi":["10.1038/s44321-025-00286-4"]}}