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Geranylgeraniol Suppresses the Expression of Adipogenic Genes and the Differentiation of Murine 3T3‐F442A and 3T3‐L1 Preadipocytes
Author(s) -
Elfakhani Manal,
Yount Sophie,
Mo Huanbiao
Publication year - 2017
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.31.1_supplement.lb394
Subject(s) - geranylgeraniol , adipogenesis , adipocyte , 3t3 l1 , biology , microbiology and biotechnology , peroxisome proliferator activated receptor , lovastatin , chemistry , endocrinology , medicine , biochemistry , adipose tissue , cholesterol , receptor , enzyme
Fundamental to the pathology of obesity is the hypertrophy and hyperplasia of adipocytes. Lipid accumulation in differentiated adipocytes is part of the adipocyte lifecycle that eventually leads to recruitment of macrophages and inflammation. We have previously shown that lovastatin, a competitive inhibitor of 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG CoA) reductase, suppresses the differentiation of murine 3T3‐F442A adipocytes via mevalonate deprivation. Tocotrienols, down‐regulators of HMG CoA reductase, inhibit adipocyte differentiation via suppression of peroxisome proliferator‐activated receptor γ (PPARγ). We hypothesize that geranylgeraniol, a diterpene known to accelerate the degradation of HMG CoA reductase, mimics the impact of lovastatin and tocotrienol in suppressing adipocyte differentiation and the expression of adipogenic genes. Oil Red O staining and Adipo‐Red assay showed that a 7‐d incubation with 2.5 – 20 μmol/L geranylgeraniol decreased the intracellular triglyceride content of murine 3T3‐F442A and 3T3‐L1 adipocytes in a concentration‐dependent manner. Geranylgeraniol also down‐regulated the expression of PPARγ, a key regulator of adipocyte differentiation, as well as the expression of adipocyte marker genes comprising adiponectin, leptin, fatty acid binding protein 4 (FABP4) and lipoprotein lipase, as measured by real‐time qPCR. Concurrently, Western‐blot showed that geranylgeraniol reduced the levels of PPARγ, FABP4 and C/EBPα proteins. No cytotoxicity was observed in preadipocyte cells incubated with geranylgeraniol (0–400 μmol/L) for 24 and 48 h. Mevalonate‐derived metabolites have crucial roles in promoting adipocyte differentiation by regulating the expression of adipogenic genes. Dietary mevalonate suppressors as anti‐adipogenesis compounds may have potential in the prevention of obesity. Support or Funding Information American River Nutrition, Inc.