Extracellular redox environments regulate adipocyte differentiation.
Oxidized extracellular redox states have been associated with many diseases related to obesity, including heart disease and diabetes, but relatively little is known about the relationship between extracellular redox states and obesity. In 3T3-L1 preadipocytes, oxidizing extracellular redox potentials (E(h)) increased intracellular and mitochondrial reactive oxygen species (ROS) production. 3T3-L1 adipocytes showed a greater response to extracellular E(h), producing more intracellular ROS, than preadipocytes. 3T3-L1 adipocytes also produced more extracellular ROS and re-regulated the extracellular E(h) to a more oxidizing state than preadipocytes. During 3T3-L1 differentiation, cellular glutathione and mitochondrial thioredoxin-2 become oxidized, suggesting that adipogenesis may be enhanced under conditions promoting intracellular and mitochondrial compartment oxidation. Under various extracellular E(h), 3T3-L1 adipogenesis, as determined by lipid accumulation and the expression of early genetic markers of adipogenesis, was sensitive to the extracellular redox environment, where it was enhanced under oxidizing conditions and lower under reducing conditions. Using a diet-induced obesity mouse model, plasma was collected before and after the 8 week diet regimens. Plasma GSH E(h) was unchanged as a consequence of weight gain but plasma cystiene (Cys) E(h) was significantly oxidized in overweight animals. Data presented here show that adipocytes/excessive adipose preferentially alter extracellular E(h) to a more oxidized state in vivo and in vitro and may promote further adipogenesis.
Imhoff
Barry R
BR
Division of Pulmonary, Allergy/Immunology, Cystic Fibrosis and Sleep, Emory Department of Pediatrics, Emory University, Atlanta, GA 30322, USA.
Hansen
Jason M
JM
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D050156:Adipogenesis / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation; D004032:Diet; D005110:Extracellular Space / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species; D005978:Glutathione