Linalool is the dominant terpene in lavender essential oil. According to this site linalool comprises almost 29% of lavender essential oil. This same site claims that linalyl acetate comprises 33% of lavender essential oil. Linalool has a hydroxyl group ( -OH ) that can form an ester bond with acetic acid to produce linalyl acetate.Linalool is a flexible molecule. The extended image came from PubChem and the enantiomeric forms from Wikipedia. Cannaconnection and other sites give strains of cannabis rich in linalool. Lavender is known for it’s ability to reduce anxiety. This post explains a publication demonstrating a completely different receptor with therapeutic potential.
Linalool and its target PPARα
Jun, H. J., Lee, J. H., Kim, J., Jia, Y., Kim, K. H., Hwang, K. Y., Yun, E. J., Do, K. R., & Lee, S. J. (2014). Linalool is a PPARα ligand that reduces plasma TG levels and rewires the hepatic transcriptome and plasma metabolome. Journal of lipid research, 55(6), 1098–1110. PMC free article html version free PDF version
This study came out of Korea University in Soul South Korea. Sung-Joon Lee was the corresponding author on this publication. We expect the Koreans to be active in any research involving natural products that can be used in aroma therapy. This paper concerns a terpene found in lavender administered by the oral route in mice. The authors used some sophisticated science to demonstrate that nuclear transcription factor PPARα really is a target of the terpene linalool. Let’s dissect this publication figure by figure. Liberty has been taken to renive some information and add more to make the publication easier to understand. On this post only the PDF version will be presented in images. For some reason converting to the PDF format brings in new images and leaves out others.
Part of Figure 1 Linalool binds PPARα
Fenofibrate is a prodrug whose liver metabolite fenofibric acid binds to and activates the transcription factor PPARα. The authors used fenofibrate as the gold standard throughout the paper.

As a point of reference, fenofibrate has an EC50 of 4 μM when it comes to activating a PPARα reporting system. Not shown is a racemic mixture of D- and L-linalool. Also not shown is proof that linalool can cross a Caco-2 monolayer suggesting that linalool can be absorbed from the GI track.
PPARα ligand binding activity was determined by LanthaScreen™ TR-FRET PPARα Coactivator Assay. Fluorescence resonance energy transfer tells us when two groups come close to one another.
- The lipid binding domain (LBD) consisted of amino acids 192–468 was synthesized and tagged to glutathione S-transferase.
- Terbium-labeled anti-PPARα antibodies absorbed 340nm light and emitted 495 nm blue light.
- fluorescein labeled coactivator PPARα coactivator PGC1α peptides (EAEEPSLLKKLLLAPANTQ). This probe absorbed 495 nm blue light if only if it were in close proximity of the terbium tagged antibody. Fluorescein emits 520 nm green light.
Recruitment of fluorescein- PPARα peptides in response to linalool or fenofibrate treatment was measured by monitoring FRET.
Figure 2 abbreviated and intro to gene targets

- PPARα Peroxisome proliferator activated receptor alpha is a transcription factor that forms heterodimers with RXRA. The triglyceride 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine is an activator.
- FATP4, Fatty acid transport protein 4 is involved in the transport of long chain fatty acids across the cell membrane and seems to be involved in acquired obesity.
- ACSL1 is an enzyme that takes a long chain fatty acid + ATP + CoA = long-chain fatty acyl-CoA with the release of AMP + diphosphate.
- ACOX1 Acyl CoA oxidase 1 catalyzes the first step of oxidation. 2,3-saturated acyl-CoA + O2 = (2E)-enoyl-CoA + H2O2
- UCP2 Uncouple protein 2 forms a H+ permeable pore in the inner membrane of the mitochondria thus uncoupling the flow of H+ through complex V that generates ATP. UCP2 overall increases the rate of metabolism because fats are reduced to CO2 to produce heat rather than ATP.
- LPL Lipoprotein lipase catalyzes the hydrolysis of triglycerides from circulating chylomicrons and very low density lipoproteins (VLDL).
- APOC3 Apolipoprotein C promotes hepatic very low density lipoprotein 1 (VLDL1) assembly and secretion while in extracellular compartments it attenuates hydrolysis and clearance of triglyceride-rich lipoproteins. This particular enzyme takes fatty acids in the opposite direction as the other five enzymes. Linalool fenofibrate decrease the levels of APOC3 while increasing the other five.
Figure 3 html, not shown
The investigators fed three different strains of mice a Western diet for three weeks. The mice were given two treatments to prevent weight gain and increases in liver weigh: linalool (100 mg/kg body weight/day), or fenofibrate (100 mg/kg body weight/day) for 3 weeks. C57BL6J mice (n = 3–5 per group) served as the controls. PPARα of one group of mice was knocked in to a third group of mice. Fenofibrate and linalool decreased the weight gain and liver weight of the wild type control and ApoE2 mice but not the PPARα mice. These mice were the source of fatty acid enzyme analysis or subsequent figures.
Figure 3 PDF version wild type mice

activation. Western-diet-fed wild type C57BL6J mice A. Fasting plasma TG levels. B: Plasma TG profiling with FPLC analysis. FPLC C. Responsive gene expressions, not shown D. protein expressions. Protein expression levels were normalized to tubulin protein. Data represent means ± SE. * P < 0.05 versus the control group. Means without common letters differed, p< 0.05.
Tubulin is a cyto skeletal protein that was assumed to not change as a result of treatment. It is a convenient way to normalize protein expression. When it comes to actual protein amounts, linalool does not always perform better than a prescription drug than, but it performs better than nothing. Linalool’s 15x increase in a fat burning UCP2 protein is most exciting.
Figure 4 a mouse model of human hyper lipoproteinemia
The investigators knocked in a gene for human apolipoprotein with an arginine to to cysteine amino acid substitution at position 158. Human homozygous carriers of this polymorphism have hyper lipoproteinemia. PubMed Note that this human gene increases the plasma triglyceride levels in mice fed a Western diet 7x as much as the wild type mice.

The linalol improvement in the TG profile (Fig 4B) is remarkable. Linalool does not perform as well as fenofibrate in target protein expression.
Fig 5 Knocking out PPARα changes the response to linalool
This post has largely ignored the gene expression data in the featured publication. Whatever protein target linalool might be interacting with to induce its ant anxiety properties, it is PPAR α that mediates improvements in triglycerides.

It is almost as if the instigators wanted to show us the immunoblots proving that knocking out PPARα abolishes the linalool response.
Looking forward
This most is not meant to offer medical advice. PubChem has a lot of information on the metabolism and excretion of this common fragrance and flavoring agent. Hopefully this post will be useful to those licensed to practice medicine.