Oxidative stress regulates adipocyte apolipoprotein e and suppresses its expression in obesity
Autor: | Doris Joy Espiritu, Theodore Mazzone |
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Rok vydání: | 2008 |
Předmět: |
Apolipoprotein E
Male medicine.medical_specialty Endocrinology Diabetes and Metabolism Adipose tissue macrophages Blotting Western Adipose tissue Gene Expression 030209 endocrinology & metabolism Biology medicine.disease_cause 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Apolipoproteins E NF-KappaB Inhibitor alpha Adipocyte Internal medicine 3T3-L1 Cells Gene expression Internal Medicine medicine Adipocytes Animals Obesity RNA Messenger Cells Cultured 030304 developmental biology 0303 health sciences Reverse Transcriptase Polymerase Chain Reaction Lipid metabolism Hydrogen Peroxide Acetylcysteine Mice Inbred C57BL Oxidative Stress Endocrinology chemistry Tumor necrosis factor alpha I-kappa B Proteins Reactive Oxygen Species Oxidative stress Obesity Studies |
Zdroj: | Diabetes |
ISSN: | 1939-327X |
Popis: | OBJECTIVE—Endogenous expression of apolipoprotein E (apoE) has a significant impact on adipocyte lipid metabolism and is markedly suppressed in obesity. Adipose tissue oxidant stress is emerging as an important mediator of adipocyte dysfunction. These studies were undertaken to evaluate the role of oxidant stress for regulation of adipocyte apoE. RESEARCH DESIGN AND METHODS—ApoE gene and protein expression in 3T3-L1 adipocytes or mature adipocytes and adipose tissue from C57/BL6 mice was evaluated after induction of oxidant stress. The response of adipose tissue and adipocytes from obese compared with lean mice to antioxidants was also assessed. RESULTS—Oxidant stress in 3T3-L1 cells or adipocytes and adipose tissue from lean mice significantly reduced apoE mRNA and protein level. Inclusion of an antioxidant eliminated this reduction. Oxidant stress was accompanied by activation of the nuclear factor-κB (NF-κB) transcription complex, and its effect on apoE was eliminated by an NF-κB activation inhibitor. Treatment of freshly isolated adipose tissue or mature adipocytes from obese mice with antioxidant increased apoE expression but had no effect on cells or tissue from lean mice. Incubation of freshly isolated adipocytes from lean mice with stromovascular cells from obese mice significantly suppressed adipocyte apoE compared with incubation with stromovascular cells from lean mice, but this suppression was reversed by inclusion of antioxidant or a neutralizing antibody to tumor necrosis factor-α. CONCLUSIONS—Oxidant stress significantly modulates adipose tissue and adipocyte apoE expression. Furthermore, oxidant stress contributes to suppression of adipocyte apoE in obesity. This suppression depends on interaction between adipose tissue stromovascular cells and adipocytes. |
Databáze: | OpenAIRE |
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