Lipid droplet is a widespread but unique hydrophobic organelle, storing neutral lipids, including polyunsaturated fatty acids (PUFAs). The abnormality of lipid droplet dynamics could cause many metabolic diseases, such as obesity and fatty liver. The nervous system has lots of lipids but few lipid droplets exist in neurons.
However, some neuronal diseases (e.g. hereditary spastic paraplegia, Parkinson's disease) are reported to have relationship with lipid droplet dysfunctions. Studying lipid droplet dynamics in neurons and its effect on neurons is important for treating neural diseases.
Recently, a study published in
EMBO Reports, conducted by Dr. HUANG Xun from the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences (CAS), revealed that lipolysis and lipogenesis regulated lipid droplet dynamics and lipid droplet accumulation reduced the available PUFAs which regulated the neurodegeneration through participating into phospholipids.
In this study, the researchers found that disturbing lipolysis or enhancing lipogenesis in neurons leads to lipid droplet accumulation in neurons of C. elegans, which is the first time to confirm lipid droplet regulation in neurons in vivo. The ectopic lipid droplets in neurons reduce the normal functions such as touch sensation but increase the ability to defend from hyperactivation-triggered neurodegeneration.
Figure 1. Mutations of key genes in lipolysis pathway cause lipid droplet accumulation in neurons of C. elegans (Image by IGDB)
Further investigation showed that PUFA synthesis pathway synergistically with lipolysis regulates neurodegeneration. Blocking PUFA incorporation into phospholipids further increases the protection from neurodegeneration.
Thus, PUFAs from lipolysis hydrolyzing and de novo synthesis participate in hyperactivation-triggered neurodegeneration through incorporation into phospholipids.
"This is a promising result since maybe one day we could alleviate neurodegeneration through adjusting the content of polyunsaturated fatty acids in our food," said Dr. HUANG.
Figure 2. PUFAs from de novo synthesis and lipid droplet hydrolyzing regulate hyperactivation-triggered neurodegeneration (Image by IGDB)
