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t,t ‐Farnesol As A Mevalonate‐Derived Inducer of Murine 3T3‐F442A Preadipocyte Differentiation
Author(s) -
Torabi Sheida,
Mo Huanbiao
Publication year - 2015
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.29.1_supplement.607.7
Subject(s) - farnesol , mevalonic acid , lovastatin , adipogenesis , glut4 , ly294002 , chemistry , downregulation and upregulation , endocrinology , biology , reductase , medicine , biochemistry , protein kinase b , glucose uptake , cholesterol , signal transduction , insulin , adipose tissue , gene , enzyme
We previously reported that lovastatin, a competitive inhibitor of 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG CoA) reductase, dose‐dependently inhibited the differentiation of murine 3T3‐F442A preadipocytes with concomitant downregulation of peroxisome proliferator‐activated receptor γ (PPARγ), leptin, fatty acid binding protein 4 (αP2), adiponectin and CCAAT/enhancer binding protein α. d ‐δ‐Tocotrienol, a vitamin E molecule and a downregulator of HMG CoA reductase, mimics lovastatin‐mediated mevalonate deprivation in inhibiting glucose uptake by 3T3‐F442A cells and the expression of GLUT4 and pAKT; the tocotrienol effect was reversed by rosiglitazone, a PPARγ agonist. We now show that t,t ‐farnesol, a mevalonate‐derived sesquiterpene, dose‐dependently (25 ‐ 75 μmol/L) increased glucose uptake and intracellular triglyceride content of 3T3‐F442A cells. Real‐time qPCR and western‐blot showed that t,t ‐farnesol increased the mRNA and protein levels of GLUT4 and PPARγ. The mRNA levels for αP2, lipoprotein lipase, and adiponectin were also upregulated, indicating the essential role of mevalonate pathway in adipocyte differentiation and upregulation of PPARγ, PI3K and adipogenic genes. GW9662 (10 µmol/L), an antagonist of PPARγ, and Ly294002 (10 µmol/L), a phosphatidyl‐inositol 3 kinase (PI3K) inhibitor, reversed the effects of t,t ‐farnesol on cellular lipid content. t,t ‐Farnesol at these concentrations did not affect the expression of HMG CoA reductase or cell viability. The mevalonate pathway may offer a novel target for modulating adipogenesis.