Title :

Serum fatty acid profiling in patients with SDHx mutations: New advances on cellular metabolism in SDH deficiency

Author(s) :

Vamecq, Joseph [Auteur]
Maladies Rares du Développement : Génétique, Régulation et Protéomique (RADEME) - ULR 7364
Masso, Vincent [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Bancel, Leo-Paul [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Jannin, Arnaud [Auteur]
Service Endocrinologie, diabétologie, maladies métaboliques et nutrition [LILLE - Endocrino]
Dessein, Anne-Frédérique [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277
Cardot-Bauters, Caroline [Auteur]
Service Endocrinologie, diabétologie, maladies métaboliques et nutrition [LILLE - Endocrino]
Pigny, Pascal [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277

Journal title :

Biochimie

Abbreviated title :

Biochimie

Volume number :

201

Pages :

196-203

Publisher :

Elsevier

Publication date :

2022-07-21

ISSN :

1638-6183

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Apart from the oncometabolite succinate, little studies have appeared on extra-mitochondrial pathways in Succinate Dehydrogenase (SDH) genetic deficiency. The role of NADH/NAD+ redox status and dependent pathways was ...
Show more >Apart from the oncometabolite succinate, little studies have appeared on extra-mitochondrial pathways in Succinate Dehydrogenase (SDH) genetic deficiency. The role of NADH/NAD+ redox status and dependent pathways was recently emphasized. Therein, fatty acid (FA) metabolism data were collected here in 30 patients with a loss of function (LOF) variant in one SDHx gene (either with a pheochromocytoma/paraganglioma (PPGL) or asymptomatic) and in 22 wild-type SDHx controls (with PPGL or asymptomatic). Blood acylcarnitines in two patients, peroxisomal biomarkers, very long-chain saturated FA (VLCFA), and C20 to C24 n-3 polyunsaturated fatty acids (PUFA), in all patients were measured by mass spectrometry. Preliminary data showed elevated even and odd long- and very long-chain acylcarnitines in two patients with a SDHB variant. In the whole series, no abnormalities were observed in biomarkers of peroxisomal β-oxidation (C27-bile acids, VLCFAs and phytanic/pristanic acids) in SDHx patients. However, an increased hexaene to pentaene PUFA ratio ([TetraHexaenoic Acid + DocosaHexaenoic Acid]/[n-3 DocosaPentaenoic Acid + EicosaPentaenoic Acid]) was noticed in patients with SDHC/SDHD variants vs patients with SDHA/SDHB variants or controls, suggesting a higher degree of unsaturation of PUFAs. Within the group with a SDHx variant, Eicosapentaenoate/Tetracosahexaenoate ratio, as an empiric index of shortening/elongation balance, discriminated patients with PPGL from asymptomatic ones. Present findings argue for stimulated elongation of saturated FAs, changes in shortening/elongation balance and desaturation rates of C20–C24 PUFAs in SDH-deficient patients with PPGL. Overall, oxidation of NADH sustained by these pathways might reflect or impact glycolytic NAD+ recycling and hence tumor proliferation.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
CHU Lille

Collections :

• Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277
• Maladies Rares du Développement : Génétique, Régulation et Protéomique (RADEME) - ULR 7364

Submission date :

2024-06-26T21:20:38Z
2024-10-29T10:39:13Z