title: Trans, trans-farnesol as a mevalonate-derived inducer of murine 3T3-F442A pre-adipocyte differentiation.
abstract: Based on our finding that depletion of mevalonate-derived metabolites inhibits adipocyte differentiation, we hypothesize that trans, trans-farnesol (farnesol), a mevalonate-derived sesquiterpene, induces adipocyte differentiation. Farnesol dose-dependently (25-75 μmol/L) increased intracellular triglyceride content of murine 3T3-F442A pre-adipocytes measured by AdipoRed™ Assay and Oil Red-O staining. Concomitantly, farnesol dose-dependently increased glucose uptake and glucose transport protein 4 (GLUT4) expression without affecting cell viability. Furthermore, quantitative real-time polymerase chain reaction and Western blot showed that farnesol increased the mRNA and protein levels of peroxisome proliferator-activated receptor γ (PPARγ), a key regulator of adipocyte differentiation, and the mRNA levels of PPARγ-regulated fatty acid-binding protein 4 and adiponectin; in contrast, farnesol downregulated Pref-1 gene, a marker of pre-adipocytes. GW9662 (10 µmol/L), an antagonist of PPARγ, reversed the effects of farnesol on cellular lipid content, suggesting that PPARγ signaling pathway may mediate the farnesol effect. Farnesol (25-75 μmol/L) did not affect the mRNA level of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme in the mevalonate pathway. Farnesol may be the mevalonate-derived inducer of adipocyte differentiation and potentially an insulin sensitizer via activation of PPARγ and upregulation of glucose uptake.
authors.affiliation: Department of Nutrition and Food Sciences, Texas Woman's University, Denton, TX 76204, USA.
authors.forename: Sheida
authors.initials: S
authors.lastname: Torabi
authors.affiliation: Department of Nutrition, Byrdine F. Lewis School of Nursing and Health Professions, Georgia State University, Atlanta, GA 30302, USA Center for Obesity Reversal, Georgia State University, Atlanta, GA 30302, USA hmo@gsu.edu.
authors.forename: Huanbiao
authors.initials: H
authors.lastname: Mo
mesh_terms: D017667:Adipocytes / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005204:Farnesol / Q000378:metabolism*; D020869:Gene Expression Profiling; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000032:analysis; D008798:Mevalonic Acid / Q000378:metabolism*; D051379:Mice; D047495:PPAR gamma / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D014280:Triglycerides / Q000032:analysis
chemical_list: D051275:Glucose Transporter Type 4; D047495:PPAR gamma; C495693:Slc2a4 protein, mouse; D014280:Triglycerides; D005204:Farnesol; D005947:Glucose; D008798:Mevalonic Acid
keywords: FABP4; Farnesol; GLUT4; HMG CoA reductase; PPARγ; adipocyte; adiponectin; differentiation; glucose; mevalonate