Monoterpene phenolic compound thymol promotes browning of 3T3-L1 adipocytes

Eur J Nutr. 2017 Oct;56(7):2329-2341. doi: 10.1007/s00394-016-1273-2. Epub 2016 Jul 18.


Purpose: Appearance of brown-like adipocytes within white adipose tissue depots (browning) is associated with improved metabolic phenotypes, and thus a wide variety of dietary agents that contribute to browning of white adipocytes are being studied. The aim of this study was to assess the browning effect of thymol, a dietary monoterpene phenolic compound, in 3T3-L1 white adipocytes.

Methods: Thymol-induced fat browning was investigated by determining expression levels of brown fat-specific genes and proteins by real-time RT-PCR and immunoblot analysis, respectively. Moreover, the molecular mechanism underlying the fat-browning effect of thymol was investigated by determining expression levels of key players responsible for browning in the presence of kinase inhibitors.

Results: Thymol promoted mitochondrial biogenesis and enhanced expression of a core set of brown fat-specific markers as well as increased protein levels of PPARγ, PPARδ, pAMPK, pACC, HSL, PLIN, CPT1, ACO, PGC-1α, and UCP1, suggesting its possible role in browning of white adipocytes, augmentation of lipolysis, fat oxidation, and thermogenesis, and reduction of lipogenesis. Increased expression of UCP1 and other brown fat-specific markers by thymol was tightly coordinated with activation of β3-AR as well as AMPK, PKA, and p38 MAPK.

Conclusion: Our findings suggest that 3T3-L1 is a potential cell model for screening browning agents. Thymol plays multiple modulatory roles in the form of inducing the brown-like phenotype as well as enhancing lipid metabolism. Thus, thymol may be explored as a potentially promising food additive for prevention of obesity.

Keywords: Adipocyte browning; Anti-obesity; Non-shivering thermogenesis; Thymol; UCP1.

MeSH terms

  • 3T3-L1 Cells
  • AMP-Activated Protein Kinases / genetics
  • AMP-Activated Protein Kinases / metabolism
  • Adipocytes / drug effects*
  • Adipocytes, Brown / drug effects
  • Animals
  • Carbon-Carbon Ligases / genetics
  • Carbon-Carbon Ligases / metabolism
  • Carnitine O-Palmitoyltransferase / genetics
  • Carnitine O-Palmitoyltransferase / metabolism
  • Genetic Markers
  • Lipolysis / drug effects
  • Mice
  • Monoterpenes / pharmacology*
  • PPAR delta / genetics
  • PPAR delta / metabolism
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism
  • Phenotype
  • Sterol Esterase / genetics
  • Sterol Esterase / metabolism
  • Thermogenesis / drug effects
  • Thymol / pharmacology*
  • Uncoupling Protein 1 / genetics
  • Uncoupling Protein 1 / metabolism


  • Genetic Markers
  • Monoterpenes
  • PPAR delta
  • PPAR gamma
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, mouse
  • Ucp1 protein, mouse
  • Uncoupling Protein 1
  • Thymol
  • Carnitine O-Palmitoyltransferase
  • AMP-Activated Protein Kinases
  • Sterol Esterase
  • Carbon-Carbon Ligases
  • acyl-CoA carboxylase