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Exercise May Promote Gene Expression of Feel-Good Chemicals

Exercise may improve mood via gene expression related to the kynurenine pathway.

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The mood-boosting effects of exercise are well established. (See here, here, here, here.) A recent study (Choi et al., 2019) by researchers from Harvard Medical School used state-of-the-art Mendelian randomization to identify a causal link between higher levels of physical activity and lower risk of depression.

Anecdotally, anyone who breaks a sweat regularly by doing cardio and lifting weights knows how good you feel after a vigorous workout. But why does physical activity have the power to boost mood and combat depression?

From a neuroscience perspective, the most common explanation for why “Sweat = Bliss” usually boils down to the power of physical activity to pump up the amount of endogenous (self-produced) feel-good chemicals (e.g., neurotransmitters and hormones) that flood the body and brain.

A new study by a team of researchers from the Department of Kinesiology at McMaster University in Canada introduces another factor that may contribute to the mood-enhancing effects of exercise. This paper, “Exercise Training Impacts Skeletal Muscle Gene Expression Related to the Kynurenine Pathway,” was published online ahead of print January 16 in the American Journal of Physiology–Cell Physiology.

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This study (Allison et al., 2019) investigated the impact of an exercise training program that combined strength training (weight-lifting) and high-intensity interval training (HIIT) on skeletal muscle gene expression of certain proteins called “transcription factors.” These proteins help regulate the gene expression of kynurenine aminotransferase (KAT) and plasma concentrations of tryptophan metabolites called "kynurenines."

Many people associate tryptophan with the folklore-based misconception that the tryptophan in turkey will make you drowsy after eating Thanksgiving dinner. However, the myth of tryptophan in turkey making people sleepy was debunked long ago.

Tryptophan is a precursor for the synthesis of serotonin. As Trisha Jenkins et al. (2016) explain, “Tryptophan is the sole precursor of peripherally and centrally produced serotonin. However, the second most prevalent metabolic pathway of tryptophan after protein synthesis is the synthesis of kynurenine, which accounts for approximately 90 percent of tryptophan metabolism.” The metabolism of tryptophan occurs almost exclusively via the kynurenine pathway.

How Does the Kynurenine Pathway Work?

The kynurenine pathway has a neuroprotective branch and a neurotoxic branch. The kynurenine pathway’s neuroprotective branch relies on gene expression of the enzyme called “KAT.” Previous research has shown that aerobic exercise and strength-training both increase KAT activity, which promotes tryptophan metabolism via the neuroprotective branch of the kynurenine pathway.

 Samo Trebizan/Shutterstock
Source: Samo Trebizan/Shutterstock

The latest research by David Allison and his McMaster colleagues revealed that 12-weeks of high-intensity interval training (HIIT) once a week combined with bi-weekly strength training sessions can significantly alter skeletal muscle gene expression of transcription factors linked to physical activity’s mood-boosting effects via the kynurenine pathway.

The researchers speculate that these findings offer yet another reason why regular exercise combats the risk of debilitating depression.

This study has some noteworthy limitations, such as a relatively small cohort size. "Larger scale exercise trials, which assess both transient and resting state biochemical changes are needed to examine how changes in these fundamental biochemical processes impact depressive symptoms," the researchers said.

"The significant exercise training-induced increase in the expression of skeletal muscle transcription factors and KAT in older adults is encouraging given the potential implications related to kynurenine pathway regulation," the authors concluded. "Future studies are warranted to explore the impact of various exercise modalities and intensities on transient changes of such factors in depressed adults."


David J. Allison, Joshua P. Nederveen, Tim Snijders, Kirsten E. Bell, Dinesh Kumbhare, Stuart M. Phillips, Gianni Parise, Jennifer Heisz. "Exercise Training Impacts Skeletal Muscle Gene Expression Related to the Kynurenine Pathway" American Journal of Physiology–Cell Physiology (First published online: January 16, 2019) DOI: 10.1152/ajpcell.00448.2018

Karmel W. Choi, Chia-Yen Chen, Murray B. Stein, Yann C. Klimentidis, Min-Jung Wang, Karestan C. Koenen, Jordan W. Smoller. "Assessment of Bidirectional Relationships Between Physical Activity and Depression Among Adults: A 2-Sample Mendelian Randomization Study." JAMA Psychiatry (First published online: January 23, 2019) DOI: 10.1001/jamapsychiatry.2018.4175

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