Fatty Aldehyde Dehydrogenase
| Autor: | Emmanuel Van Obberghen, Damien Demozay, Sophie Grillo, Jean-Christophe Mas, Luciano Pirola, Carine Chavey, Stéphane Rocchi |
|---|---|
| Přispěvatelé: | INSERM U145, IFR 50, Faculté de Médecine, Avenue de Valombrose, 06107 Nice Cedex 2, France. |
| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
medicine.medical_specialty
medicine.medical_treatment [SDV]Life Sciences [q-bio] medicine.disease_cause Biochemistry Lipid peroxidation 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Insulin resistance Internal medicine Adipocyte medicine Glucose homeostasis Molecular Biology ComputingMilieux_MISCELLANEOUS 030304 developmental biology chemistry.chemical_classification 0303 health sciences Reactive oxygen species biology Insulin Cell Biology medicine.disease Insulin receptor Endocrinology chemistry 030220 oncology & carcinogenesis biology.protein Oxidative stress |
| Zdroj: | Journal of Biological Chemistry Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2004, 279 (8), pp.6261-6270. ⟨10.1074/jbc.M312062200⟩ |
| ISSN: | 0021-9258 1083-351X |
| DOI: | 10.1074/jbc.M312062200⟩ |
| Popis: | Phosphatidylinositol 3-kinase signaling regulates the expression of several genes involved in lipid and glucose homeostasis; deregulation of these genes may contribute to insulin resistance and progression toward type 2 diabetes. By employing RNA arbitrarily primed-PCR to search for novel phosphatidylinositol 3-kinase-regulated genes in response to insulin in isolated rat adipocytes, we identified fatty aldehyde dehydrogenase (FALDH), a key component of the detoxification pathway of aldehydes arising from lipid peroxidation events. Among these latter events are oxidative stresses associated with insulin resistance and diabetes. Upon insulin injection, FALDH mRNA expression increased in rat liver and white adipose tissue and was impaired in two models of insulin-resistant mice, db/db and high fat diet mice. FALDH mRNA levels were 4-fold decreased in streptozotocin-treated rats, suggesting that FALDH deregulation occurs both in hyperinsulinemic insulin-resistant state and hypoinsulinemic type 1 diabetes models. Moreover, insulin treatment increases FALDH activity in hepatocytes, and expression of FALDH was augmented during adipocyte differentiation. Considering the detoxifying role of FALDH, its deregulation in insulin-resistant and type 1 diabetic models may contribute to the lipid-derived oxidative stress. To assess the role of FALDH in the detoxification of oxidized lipid species, we evaluated the production of reactive oxygen species in normal versus FALDH-overexpressing adipocytes. Ectopic expression of FALDH significantly decreased reactive oxygen species production in cells treated by 4-hydroxynonenal, the major lipid peroxidation product, suggesting that FALDH protects against oxidative stress associated with lipid peroxidation. Taken together, our observations illustrate the importance of FALDH in insulin action and its deregulation in states associated with altered insulin signaling. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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