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Mechanism Underlying Cardiac Rhythm Disturbance-mediated Fat Accumulation In C.elegans Exposed To Light

Posted on:2021-04-01Degree:MasterType:Thesis
Country:ChinaCandidate:Y DuFull Text:PDF
GTID:2480306197955369Subject:Biochemistry and Molecular Biology
Abstract/Summary:
In the process of long-term changes and movements of the earth,the rotation of the earth makes it appear to change around day and night for about 24 hours,and therefore brings about the day and night changes in environmental factors such as light and temperature.In order to adopt this change in the day and night environment,most organisms have evolved a physiological and behavioral rule in harmony with it,namely the biological clock.It is an internal rhythm required to maintain the normal activities of organisms,and it exists in many organisms.Light is the main stimμlus in the circadian system,the main synchronizer of the circadian clock and the circadian rhythm.It can reset or synchronize the circadian system of the body.Specific retinal cels can sense the intensity of the light and send a signal to the supranational nucleus To regμlate the interaction between biological rhythms at various levels.There are a series of circadian clock-related genes in mammals,including Bmal,Nr1d1,Per1/2/3,and Cry1/2,etc.These genes form a negative feedback loop to play a role in physiological prosesses.C.elegans,one of the model organisms,has 60% to 80% homology with human genes.A variety of homologous genes of circadian clock genes have also been found in nematodes,including Bmall homologous genes aha-1,Per homologous genes lin-42,Nr1d1 homologous genes nhr-85,timeless homologous genes tim-1,and double-time homologous genes kin-20.Currently,the role of the biological rhythms in C.elegans remains largely unclear.In this study,we found that under continuous light exposure conditions,C.elegans exhibited shortened lifespan and aging phenotype,such asreduced head swing frequency and reduced pharyngeal twitch frequency.Treatment of nematodes under continuous light for 12 hours caused significant accumulation of fat.Meanwhile,we found that the mRNA levels of the circadian clock homologous genes aha-1,lin-42,nhr-85,and kin-20 were reduced,indicating that changes in light are likely to cause nematode circadian clock and lipid metabolism disorders.Indeed,under dark conditions,silencing of aha-1,nhr-85,and kin-20 by RNAi also induced fat accumulation in nematodes.Fat accumulation was also observed in the lin-42(ok2051)mutants.In contrast,silencing of tim-1 inhibited fat accumulation in worms with continuous light exposure,suggesting that the regulation of fat accumulation by tim-1 is independent of aha-1,lin-42,nhr-85,and kin-20.Further study found that the transcription factor DAF-16/FOXO was translocated into nuclear and activated by light exposuretranslocation.DAF-16 mediated fat accumulation under light treatment.Likewise,knockdown of daf-16 by RNAi suppressed fat accumulation in worms subjected to aha-1,lin-42,nhr-85,and kin-20 RNAi under dark conditions.The above results indicates that light will inhibit the expression of circadian clock homologous genes and further activate the transcription factor DAF-16 / FOXO to cause fat accumulation.In addition,we also found that.Finally,we found that silencing of the photoreceptor genes lite-1 and gur-3 inhibited fat accumulation,and nuclear translocation of DAF-16 in worms exposed to light,indicating that LITE-1 and GUR-3 plays a role in fat accumulation by sensitizing light.In summary,our study reveals that continuous light downregulates the expression of major rhythm genes via photoreceptors,leading to activation of DAF-16.The latter mediates fat accumulation.Our data provide new insight into the mechanism of weight gain caused by sleep loss.
Keywords/Search Tags:Biological clock, Light, Fat metabolism, Photoreceptor
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