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 dosedependently (25-75 lmol/L) increased intracellular triglyceride content of murine 3T3-F442A pre-adipocytes measured by AdipoRed TM 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 g (PPARg), a key regulator of adipocyte differentiation, and the mRNA levels of PPARg-regulated fatty acid-binding protein 4 and adiponectin; in contrast, farnesol downregulated Pref-1 gene, a marker of pre-adipocytes. GW9662 (10 mmol/L), an antagonist of PPARg, reversed the effects of farnesol on cellular lipid content, suggesting that PPARg signaling pathway may mediate the farnesol effect. Farnesol (25-75 lmol/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 PPARg and upregulation of glucose uptake.

Original Research: Polyphenols extracted from grape powder induce lipogenesis and glucose uptake during differentiation of murine preadipocytes

“…In addition, we have previous experience with 3T3-F442A cell lines using the same methods. 15 Adipocyte differentiation is a well-orchestrated multi-step process involving several genes. 10 Two transcriptional factors, peroxisome proliferator-activated receptor g (PPARg) and CCAAT/enhancer binding protein a (C/EBPa) 9,10 are known as major regulators of adipogenesis and are at the core of the adipogenic cascade.…”