Oxidative stress regulates adipocyte apolipoprotein e and suppresses its expression in obesity.
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.


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-kappaB (NF-kappaB) transcription complex, and its effect on apoE was eliminated by an NF-kappaB 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-alpha.


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.
Espiritu
Doris Joy
DJ
Department of Medicine, University of Illinois, Chicago, Illinois, USA.
Mazzone
Theodore
T
D041721:3T3-L1 Cells; D000111:Acetylcysteine / Q000494:pharmacology; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D015153:Blotting, Western; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology; D020672:I-kappa B Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000072000:NF-KappaB Inhibitor alpha; D009765:Obesity / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001057:Apolipoproteins E; D020672:I-kappa B Proteins; C000606205:Nfkbia protein, mouse; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D000072000:NF-KappaB Inhibitor alpha; D006861:Hydrogen Peroxide; D000111:Acetylcysteine