Nerve cell lipolysis can promote nerve cell degeneration

  Fat droplets are organelles. The internal environment of eukaryotic cells is hydrophobic and provides the basis for cell material and energy metabolism by storing and releasing lipids. The dynamic changes of lipid droplets are related to various metabolic abnormalities, such as obesity, fatty liver and diabetes. According to reports, certain neurodegenerative diseases, such as Parkinson's disease, Huntington's disease and hereditary spastic diseases, are related to abnormal lipid droplet dynamics, but are related to abnormal lipid droplet dynamics and neurological diseases. This relationship is still unknown. Most eukaryotic cells have lipid droplets, but under normal circumstances, there are fewer lipid droplets on nerve cells in the body. Studying the dynamics of nerve cell lipid droplets in the body and its relationship with neurological diseases is of great significance for elucidating the regulation mechanism of neurolipid metabolism and treating neurological diseases.

  Huang Xun, a researcher at the Institute of Genetic Development Biology, Chinese Academy of Sciences, uses various model organisms to analyze the dynamic changes of lipids in various tissues and organs during individual growth and aging (Bietal). , CellMetabolism2014; Fanetal. , PLoSGenetics2017; Dingetal. , EMBOJ2018; Yaoetal. , CellReports2018; Yangetal. , PLoSGenetics2019). In order to study the regulation mechanism of lipid metabolism in nerve cells, the researchers established a nerve cell-specific lipid droplet labeling system. Through genetic screening, we found that mutations in the main lipolysis pathway genes atgl-1 and lid-1 may make nematode nerve cells more sensitive. The abnormal accumulation of multiple lipid droplets and lipolytic nerve tissue can autonomously adjust the dynamics of lipid droplets. Abnormal synthesis of lipids in nerve cells can also affect the dynamics of fat droplets in somatic cells. Therefore, lipid synthesis and lipolysis in nerve cells jointly regulate the dynamics of lipid droplets in nerve cells to maintain a lower lipid droplet level. After observing whether the abnormal accumulation of lipid droplets in nerve cells affects the normal function and degeneration of nerve cells, the accumulation of lipid droplets in nerve cells can make sensory neurons sensitive to external mechanical stimulation. It has been found to reduce it and block ion channels. Excessive activation of the protein MEC-4 leads to degeneration of nerve cells. Combining lipidomics and genetic analysis with existing literature reports, we found that polyunsaturated fatty acids are involved in the regulation of this process. Mechanically, nerve cell lipolysis participates in the formation of phospholipids and provides polyunsaturated fatty acids that promote nerve cell degeneration. This study found that adjusting the content of polyunsaturated fatty acids and the balance of triglycerides and phospholipids affects the degeneration of nerve cells caused by excessive activation of ion channel proteins. it is. It plays an important role in the treatment of neurodegenerative diseases. Related research results were published online in EMBOReports (DOI: 10.15252/embr.202050214), in which neurolipolysis involves PUFA-mediated neurological function and degeneration. The first author of the paper, Yan Leiay, is the first author of the paper, and Huang Xu (Guang Xu) is the corresponding author of the paper, and Din Mei, a researcher at the Institute of Genetic Development (DIST). participate. The research work was funded by the National Natural Science Foundation of China and the Ministry of Science and Technology.