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Effects Of Photoperiod And Melatonin Administration On Metabolism Of Adipose Tissue Of Rats

Posted on:2006-12-15Degree:DoctorType:Dissertation
Country:ChinaCandidate:L H YangFull Text:PDF
GTID:1104360182472514Subject:Internal Medicine
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BackgroudMelatonin is a neurohormone synthesized and secreted at night mainly by the pineal gland in vertebrates. It affects various physiological functions such as seasonal reproduction, thermoregulation and energy metabolism in mammals and particularly in seasonal mammalian species. In the latter, melatonin is known to affect body mass, adiposity and both energy intake and expenditure. Thus, opposite results are observed in Siberian and Syrian hamsters, in which melatonin decreases or increases body fat mass, respectively. Furthermore, a melatomn agonist and antagonist stimulates or lowers seasonal obesity in the garden dormouse. The exact mechanism of action is not yet fully understood. A direct effect of melatonin on brown adipocytes or an indirect effect via the sympathetic nervous system have both been demonstrated.Although these effects are less clear in non-photoperiodic species, there are reports suggesting such a role for melatonin in rats. Human and rat pineal melatonin secretion decline with aging, whereas visceral fat and plasma insulin levels increase. Melatonin modulates fat metabolism in some mammalian species, so these aging-associated melatonin, fat and insulin changes could be functionally related. In obese Zucker rats raised in a long photoperiod, body mass was heavier than in those maintained in a short photoperiod whereaslean rats were not sensitive to these changes. More directly, melatonin has been shown to decrease body weight in middle- aged rats. Taken overall, these data suggest that melatonin has effect in rats that it alters body fat mass which is already elevated, as in aging or in genetically obese rats. The present study was undertaken to test this hypothesis, in a model considered to be relevant in human species, i.e. rat treated with different dose melatonin or light condition (SD or LD). In this study, by several experiment technologies and methods, we managed to resolve some questions as follows: 1. Is there any difference of the body weight and visceral fat between rats in difference group? 2. Which has the relation with the change of body weight and visceral fat, the serum concentration of leptin, insulin, TG? 3. Whether melatonin recepors exist in adipocyte? Which subtypes they are? If exist, do the expression of melatonin receptors mRNA have a difference or not? 4. Observe whether or not there is some difference of the beta-3 adrenal receptor in adipocyte. This is the evidence of indirect effect of melatonin on the adipocyte. 5. What is the change of the melatonin receptors in hypothalamus? So, this study was planned to investigate the possible mechanism about how the melatonin or photoperiod impact on the energy balance.Methodsl.The effects of melatonin and photoperid on energy metabolism of rats(1) Rats were treated with different doses of melatonin(10mg melatonin/Kg/d and 0.2mg melatonin/Kg/d) for 3 weeks. Body weight, visceral fat, triglyceride, leptin, and insulin were measured.(2) After being treated with SD(light:dark=8:16)or LD(light:dark=16:8) for 3 weeks, body weight, visceral fat, triglyceride, leptin, and insulin of rats were measured.2. To investigate the difference expression of mtl, MT2 and beta-3 adrenal receptor onadipocyte of ratsAfter being treated with difference dose of melatonin and difference photoperiod, weextracted the total RNA of the adipose tissue and synthesized the primer of mtl, MT2 andbeta-3 adrenal receptor and analyzed the mRNA of melatonin receptor and beta-3 adrenalreceptor by real time RT-PCR.3. The effects of melatonin and photoperid on mtl and MT2 in hypothalamus of rats After being treated with different doses of melatonin and difference photoperiod, wesliced up the hypothalamus tissue lmm away from brain of rats to detect the melatoninreceptor with SP immunohistochemistry method after the slices were fixed, dehydrated andembeded. Results1. High doses of melatonin decreased body weight, visceral fat, leptin of rats, but it had no effects on insulin and triglyceride level.2. High doses of melatonin increased beta-3 adneral receptor mRNA expression and decreased mtl mRNA expression in adipocyte of rats, but there were no change in MT2 mRNA expression.3. High doses of melatonin decreased mtl mRNA expression in hypothalamus tissue of rats, but there were no change in MT2 mRNA expression.4. There were not significant difference in body weight, visceral fat, leptin, insulin and triglyceride of rats treated with low dose melatonin and any photoperiod compared with other groups. So did with the mtl, MT2 mRNA expression in hypothalamus tissue of rats and mtl, MT2 and beta-3 adneral receptor mRNA expression in adipocyte of rats.Conclusions1. Melatonin had an effect on adipose tissue metabolism, but it dependent on the dose of melatonin. High doses of melatonin had but low dose not. The reason why the change of photoperiod had no effect on adipose tissue metabolism is that the 3 week period study is not so long enough to make a chang.2. The effect of high doses of melatonin on adipose tissue is that it decreased body weight and Periepididymal adipose tissue. We did not study on whether or not it had an effect on Subcutaneous adipose tissue.3. The effect which high doses of melatonin decreased body weight and Periepididymal adipose tissue could have a relation with leptin level in serum. The fact which TG level had no change suggested that the effect above could be just a local change of adipose tissue metabolism.4. High doses of melatonin had no effects on insulin. We presumed this could be relation on the anti-oxidation function of melatonin which could improved insulin resistin.5. The mtl is the receptor that is relation to season rhythm. This is the reason why MEL decreased mtl mRNA expression on adipocyte. We could infered that sympathetic nerve also had an effect on adipose tissue metabolism from increasing of beta-3 adrenal receptor on adipocyte.6. High doses of melatonin decreased mtl protein expression in hypothalamus tissue of rats, but there were no change in MT2 mRNA expression. This suggested that the mtl take part in energy metabolism.
Keywords/Search Tags:Melatonin, photoperiod, Rat, adipose tissue, energy metabolism, melatonin receptor
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