|Abstract: ||Although the beneficial effects of omega-3 fatty acid in reducing the risk of various of human diseases, such as hypertriglyceridemia and nonalcoholic fatty liver disease, have been demonstrated in clinical and pre-clinical studies, the mechanism of its action is poorly understood.
several studies has been reported that Dietary supplementation with fish oil induces many changes in plasma TG profile.
N-3 fatty acid found in fish oil has been reported that reduce plasma TG and VLDL lev- els. Intercellular lipid droplets is the key regulator of plasma fatty acids and lipoproteins level.
Here we show that n-3 fatty acid supplementation triggers intercellular lipid droplets degradation independent from known fatty acid mobilization pathways namely lipophagy and lipolysis .
ATGL and HSL are consider as two major lipolysis enzymes.SiRNA study of these two lipolysis enzymes did not attenuate lipid droplets degradation.
Lipophagy has been reported as a selective mechanism for degradation of lipid droplets during the starvation condition. Knock down of autophagy (macroautophagy) related pro- teins, could not block degradation of intercellular lipids by EPA.
Degradation of lipid droplets is lysosomes dependent and requires lysosomal motility machinery. Lysosomes are interacting directly with lipid droplets during the process that is similar to kiss and run pattern.
The morphological examination of this process by electron microscopy indicated its re- semblance to microautophagy like structure.
Importantly, (over expression) Arl8b which has been shown that play a role in peripheral distribution of lysosomes along with FYCO1, specifically accelerates the effect of EPA on degradation of intercellular lipid droplets independent from its role in engagement of lysosomal plus end distribution.
in particular, Arl8b recruited HOPS protein complex in EPA dependent fashion and si- lencing of HOPS complex interfered with normal lysosomal degradation of lipid droplets. Thus, this finding reveals new mechanism for intercellular lipid mobilization and offer an explanation for the therapeutic benefits of omega-3 fatty acids.|