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bioRxiv · 10.1101/2021.08.25.457630

The omega-3-fatty acid docosahexaenoic acid modulates intracellular myo-inositol and its biosynthetic genes.

Murray, M.·Ok, T.·Kang, H.·Lee, J. Y.·Kim, B.·Sung, H.·Tait, T.·Colon Hidalgo, D.·Guzman, Y.
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Abstract

Bipolar disorder is a debilitating mood disorder characterized by recurring episodes of mania and depression. It affects 2.6% of adults and has a lifetime prevalence among adults of 3.9%. Current mood stabilizers are not always effective and/or are not well tolerated by many patients; thus, there is a need to develop or identify more effective and less harmful treatments. Omega-3-fatty acids have been shown to be effective in the treatment of bipolar disorder; however, their mechanism of action is unknown. Myo-inositol depletion has been hypothesized as the mechanism by which mood stabilizers exert their therapeutic effect. Using an enzymatic assay, we determined intracellular myo-inositol levels increased more than 2-fold when cells were grown in the presence of the omega-3 fatty acid docosahexaenoic acid (DHA). RT-qPCR was used to characterize the effects of DHA on genes in the myo-inositol biosynthetic pathway. We show DHA increases relative expression and has a concentration-dependent impact on INO1 and INM1, which encode myo-inositol-1-phosphate synthase and myo-inositol monophosphate 1-phosphatase, respectively. We therefore conclude that the omega-3-fatty acid DHA exerts its therapeutic effect on bipolar disorder by increasing intracellular myo-inositol, which may be accomplished by upregulating its biosynthetic genes.

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Murray, M., Ok, T., Kang, H., Lee, J. Y., Kim, B., Sung, H., Tait, T., Colon Hidalgo, D., Guzman, Y.. 2021-08-25. The omega-3-fatty acid docosahexaenoic acid modulates intracellular myo-inositol and its biosynthetic genes.. https://doi.org/10.1101/2021.08.25.457630

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