The Effect Of Lysosome Activity On Fat Deposition In Caenorhabditis Elegans

Excessive energy intake induces fat accumulation,and finally leads to obesity and associated metabolic diseases.As a highly acidic cellular organelle,lysosomal activity has classically been related to the degradation of dysfunctional cell components.Additionally,in mammalian cells,lysosome has recently been implicated in nutrient sensing and energy metabolism during starvation.However,whether lysosomal activity plays a critical role in excess nutrient-induced fat deposition remains unclear.In this study,utilizing Caenorhabditis elegans(C.elegans),we investigate the role of lysosomal activity in overnutrition-induced fat deposition.By adding glucose and palmitic acid into nematode growth medium(NGM)at L1 or L4 larval stages,we established the long-term or short-term model of fat accumulation.Along with the increased fat deposition,lysosomal numbers and acidification levels were also elevated,suggesting that lysosome might regulate nutrient-induced fat deposition.Using lysosomal inhibitor chloroquine and the mutant of hlh-30 that is a key gene involving in lysosomal biosynthesis to inhibit the activity of lysosome,we found that lysosome inhibition significantly reduced C.elegans fat deposition.Utilizing various mutants of aak-2,daf-15 and rsks-1,which are key factors in lysosomal nutrient sensing and lipid metabolism-related signaling pathways,we explored that m TORC1 signaling pathway mediated the effect of lysosome on nutrient-induced fat deposition in C.elegans.The results show that the role of lysosomal activity in nutrient-induced C.elegans fat accumulation.Additionally,in standard NGM plate,we investigated the effects of lysosome activity on basal fat deposition in eat-2,daf-2 and aak-2 mutants,which are the key molecules related to fat metabolism.The result show that lysosomal activity regulates basal fat deposition in C.elegans was via dietary restriction signaling pathway.In conclusion,utilizing C.elegans,the dissertations reveal that lysosome regulate nutrient-induced fat accumulation through m TORC1 signaling pathway.