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Effects Of Sea Cucumber Saponins On Biological Clock And Circadian Rhythm Of Genes Involve In Lipids Metabolism In Mice

Posted on:2015-09-25Degree:MasterType:Thesis
Country:ChinaCandidate:M WenFull Text:PDF
GTID:2284330431464694Subject:Food processing and safety
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With the variation of the life style, the morbidity of metabolic syndrome is rising,and its pathogenesis, prevention and treatment have become the research hotspot inthe modern society. Disorder of lipids metabolism, a kind illness of metabolicsyndrome, including obesity, hyperlipidemia, fatty liver, and so on. Recent researchfound that intimate relationship between rhythm disorder and metabolic imbalance.Circadian rhythm produced by clock genes, the master pacemaker in thesuprachiasmatic nucleus (SCN) of the hypothalamus entrained primarily by light andslave clock in most peripheral cell types entrained by feeding mainly. Under normaloperation, the master pacemaker and the slave clock are coupling, and synchronouschange along with the light/dark cycle. It’s reported that altering the innatefeeding-time could entrain the peripheral circadian oscillator but could not ensure theentrainment to master clock in SCN. Our previous research discovered that seacucumber saponins (SCS) have the bioactivities of weight loss, anti-hyperlipidemiaand alleviating NAFL (non-alcoholic fatty liver). However, the mechanism ofimproving lipid metabolism for SCS remains unclear now. This article studied theeffect of SCS on circadian rhythm and found a new mechanism for SCS to improvelipids metabolism disorder.Firstly, we explored the effect of SCS on the hepatic genes in mice by the genechip technology of high-throughput screening. As a result, SCS could significantlyinfluence some hepatic metabolic pathways: Glycosaminoglycan biosynthesis-chondroitin sulfate, Glycosphingolipid biosynthesis, Nitrogen metabolism,Nitrogenmetabolism, especially on circadian rhythm in which the influenced genes account for40.91%of the total. And the results provided a theoretical reference for later studyrelated to the variation of circadian clock genes in24h.Secondly, we investigated the expression of clock genes in brain and liver, andcompared them under two different feeding ways, daytime/nighttime feeding. Theresult suggested that lower expression level of brain clock genes in thedaytime/nighttime feeding way, but similar expression pattern between nighttimefeeding and ad libitum. Compared with the ad libitum, both daytime feeding andnighttime feeding could improve the expression of hepatic clock genes. Furthermore,circadian rhythm under nighttime feeding was similar with ad libitum but contrarywith daytime feeding.Last, we explored the effect of SCS on the genes involved in circadian rhythmand lipids metabolism under daytime/nighttime feeding. And we conclude that SCS had a marked impact on them.1) Under the nighttime feeding condition, the effect ofSCS on the expression of clock genes in brain is visible. However, SCS slightlychange the circadian pattern of hepatic clock genes with up/down-regulating thelevels of them. SCS inhibited the hepatic lipids synthesis by uncoupling the hepaticlipids synthesis from feeding and stimulated the oxidation of hepatic fatty acid byimproving the level of related genes.2) Under the daytime feeding condition, SCSobviously altered the clock genes expression in brain and prevented the uncouplingbetween master clock and slave clock by partly synchronizing the expression of clockgenes in brain and liver. SCS held back the uncoupling caused by daytime feeding andelevated the expression levels of genes involved in lipids metabolism therebypromoting the integral lipids metabolic level in liver. In addition, the daily pattern ofhepatic clock-controlled genes was opposite in different feeding condition, SCS justsignificantly lifted their amplitude but did not change their daily pattern under thedaytime/nighttime feeding condition. It suggested that the circadian pattern wascorrelated with the feeding time.This paper firstly discovered that SCS could affect the circadian rhythm, alsocompared the effects of SCS on clock genes expression and hepatic lipids metabolicgenes expression, providing a new thought and theory basis for the activity researchon sea cucumber saponins.
Keywords/Search Tags:circadian rhythm, feeding mode, sea cucumber saponins, clockgenes, lipids metabolism
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