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HIV Protease Inhibitors Differentially Regulate PPARγ expression in Adipocytes
Author(s) -
Pecora Beth S,
Zha Weibin,
Hylemon Phillip B,
Wabitsch Martin,
Zhou Huiping
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.477.2
Subject(s) - peroxisome proliferator activated receptor , adipocyte , lipid metabolism , biology , troglitazone , microbiology and biotechnology , western blot , small interfering rna , lipodystrophy , microrna , receptor , rna , endocrinology , adipose tissue , gene , biochemistry , human immunodeficiency virus (hiv) , immunology , viral load , antiretroviral therapy
HIV protease inhibitor (PI)‐induced dysregulation of lipid metabolism is a major concern in the clinic. The peroxisome proliferator‐activated receptor γ (PPARγ) plays a pivotal role in regulating the expression of key genes involved in lipid metabolism and activating adipocyte differentiation. We have previously shown that individual HIV PIs had different effects on PPARγ expression and adipocyte differentiation. The aim of this study was to examine the potential cellular mechanisms by which HIV PIs regulate PPARγ expression in adipocytes. Methods Mouse 3T3‐L1 and human SGBS adipocytes were used in this study. The interaction between RNA binding proteins, HuR and CUGBP1, and PPARγ mRNA was identified by pull‐down assay and immunoprecipitation followed by real‐time RT‐PCR. The intracellular protein levels of HuR and CUGBP1 were measured via Western Blot analysis. Luciferase reporters containing PPARγ promoter, coding region, or 3’untranslated region were utilized to identify the potential mechanisms by which HIV PIs regulate PPARγ expression. Results HIV PIs differentially regulate the expression of PPARγ in adipocytes. Conclusions HIV PI‐mediated dysregulation of PPARγ expression may represent a critical mechanism by which HIV PIs induce dyslipidemia, lipodystrophy and metabolic syndrome. This work was supported by NIH R01 and F30 grants.