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The impact of geranylgeraniol on the differentiation of murine 3T3‐F442A preadipocytes
Author(s) -
Elfakhani Manal,
Yeganehjoo Hoda,
Shah Anureet,
Hussein Deema,
Mo Huanbiao
Publication year - 2013
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.27.1_supplement.lb320
Subject(s) - geranylgeraniol , adipogenesis , adipocyte , biochemistry , microbiology and biotechnology , biology , gene knockdown , chemistry , adipose tissue , enzyme , gene
The statins, competitive inhibitors of 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG CoA) reductase, suppress the differentiation of adipocytes via mevalonate deprivation. We hypothesize that geranylgeraniol, a diterpene shown to accelerate the degradation of HMG CoA reductase, mimics the impact of lovastatin in adipocytes by suppressing adipocyte differentiation and adipogenic gene expression. Adipo‐Red assay and oil Red O staining showed that a 7‐d incubation with 2.5 – 20 μmol/L geranylgeraniol dose‐dependently reduced the intracellular triglyceride content of murine 3T3‐F442A adipocytes. Concomitantly, geranylgeraniol down‐regulated the expression of peroxisome proliferator‐activated receptor γ (PPARγ), a key regulator of adipocyte differentiation as analyzed by real‐time qPCR. The expression of adipocyte marker genes including adiponectin, leptin, fatty acid binding protein 4 and lipoprotein lipase was also suppressed by geranylgeraniol. No changes in cell viability were observed in 3T3‐F442A cells incubated with geranylgeraniol (0–400 μmol/L) for 24 and 48 h. Mevalonate‐derived metabolites have essential roles in promoting adipocyte differentiation and adipogenic gene expression. Dietary mevalonate suppressors may have potential as anti‐adipogenesis compounds.