Biochemical and Biophysical Research Communications
Hypoxia dysregulates the production of adiponectin and plasminogen activator inhibitor-1 independent of reactive oxygen species in adipocytes
Section snippets
Materials and methods
Reagents. Dimethyloxallyl glycine (DMOG) was purchased from Cayman Chemicals (Ann Arbor, Michigan, USA). N-Acetyl-l-cysteine (NAC), catalase, and hydrogen peroxide (H2O2) are the products of Sigma (St. Louis, MO, USA). The anti-actin antibody and the anti-HIF-1α monoclonal antibody were from Santa Cruz Biotechnology (Santa Cruz, CA, USA), and R&D Systems (Minneapolis, MN, USA), respectively. Trizol Reagent and Superscript first-strand cDNA synthesis system were purchased form Promega (Madison,
Ambient hypoxia markedly decreases adiponectin production, but increases PAI-1 expression in 3T3-L1 adipocytes
To examine the effects of hypoxia on the expression of adiponectin and PAI-1, fully differentiated 3T3-L1 adipocytes were cultured in 1% O2 atmosphere or in normoxia condition for different time periods. Methyl thiazole tetrazolium (MTT) assay revealed that treatment with hypoxia had no significant effect on cell viability (data not shown). Quantitative real-time PCR demonstrated that hypoxia significantly decreased the steady-state mRNA abundance of the adiponectin gene in a time-dependent
Discussion
Hypoadiponectinemia and elevated plasma levels of PAI-1 are the two important biochemical hallmarks in the pathogenesis of obesity-related disorders, especially type 2 diabetes and cardiovascular diseases [9], [10], [21]. Our present study demonstrated that hypoxia could markedly decrease the production of adiponectin and increase the expression of PAI in adipocytes, a major site for synthesizing these two adipokines. Accumulating evidence suggests that local hypoxia occurs in enlarged adipose
Acknowledgments
This work was supported by Hong Kong Research Council Grant HKU (7486/04M), and a research and conference grant from the University of Hong Kong (To A. Xu), Sun Chieh Yeh Heart Foundation, and the 973 program of China (2004CB720102).
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