Lipid Metabolism Contributes to Intellectual Disability

A research team has demonstrated that there is a lipid metabolism enzyme that regulates the activity of neural stem/progenitor cells (NSPC) throughout an individual’s life. Previously, researchers understood that altered NSPC activity and neurodevelopmental defects were linked to intellectual disability. This new study, published in Cell Stem Cell, showed for the first time that an enzyme, known as fatty acid synthase (FASN), specifically may be responsible for causing cognitive deficits.¹

In conducting the study, the researchers used mouse models and human cerebral organoids, which are cell cultures of the brain that are created from human embryonic stem cells. The researchers then altered the genetic information of both in order for each to present the specific mutation that had previously been found in people with known cognitive deficits.¹

“This approach allows us to analyze the effects of the defective enzyme in the brains of adult mice and during early human brain development in parallel,” said Sebastian Jessberger, PhD, professor at the Brain Research Institute at the University of Zurich (UZH), in a press release. “The new discoveries regarding learning and memory deficits in people were only made possible by linking our research on animal models and in human cells.”²

The results of both models suggested to the researchers that altered lipid metabolism contributed to intellectual disability, according to the study.¹

Furthermore, the newly identified FASN helps to explain how lipid metabolism is able to regulate NSPC activity and influence brain development, providing a “blueprint” for future research into the activity of brain stem cells and their involvement in cognitive processes. This will also help researchers in the future to better understand how to focus studies on diseases that are currently not well understood.¹

“We hope that it will be possible to control stem cell activity therapeutically to use them for brain repair—for example for the future treatment of cognitive disorders or in association with diseases that involve the death of nerve cells,” Jessberger said in a press release. These conditions may include Parkinson disease or Alzheimer disease.²

REFERENCES

• Bowers M, Liang T, Gonzalez-Bohorquez D, et al. FASN-Dependent Lipid Metabolism Links Neurogenic Stem/Progenitor Cell Activity to Learning and Memory Deficits. Cell Stem Cell. 2020. doi: 10.1016/j.stem.2020.04.002.
• Lipid metabolism controls brain development [news release]. ScienceDaily. May 7, 2020. sciencedaily.com/releases/2020/05/200507131334.htm. Accessed May 11, 2020.