褪黑素调节雄性大鼠脂肪代谢的研究

doi:10.11843/j.issn.0366-6964.2017.09.014

摘要/Abstract

摘要：

旨在研究褪黑素（Melatonin，MT）对雄性大鼠脂肪代谢的影响及其对不同脂肪代谢酶/因子的作用，初步揭示其调节脂肪代谢的机理。选择20只日龄、体重接近的SD雄性大鼠随机平均分为2组，分别为对照组（ND）和褪黑素处理组（ND+MT）。ND+MT组除饲喂正常的饲粮外，每天灌服10 mg·kg^-1 BW的MT溶液。试验60 d后采血，分析血液生化、激素及脂代谢相关指标；试验结束后处死大鼠，摘取肝组织，分离腹部各部位脂肪组织并称重，采集肝组织样品用于基因芯片检测和相关分子分析。结果表明：1） ND+MT组大鼠肝重、肝指数、大网膜重、大网膜指数、附睾脂肪重显著降低（P<0.05）。血清低密度脂蛋白显著降低（P<0.05），高密度脂蛋白、总胆固醇含量下降，极低密度脂蛋白含量升高；肝组织中长链脂肪酸含量显著降低（P<0.05）。2）基因芯片和荧光定量PCR检测结果表明，肝组织中脂肪分解相关因子CPT1的mRNA表达显著上调（P<0.05），脂肪分解相关酶ALDH3a2的mRNA表达升高（0.05 < P < 0.1），脂肪合成相关酶ACSL3、FAS的mRNA表达显著下调（P<0.05）。结果提示，MT可显著影响脂肪的代谢，减少内脏脂肪的含量，其机制与相关激素及肝脂肪代谢相关酶（因子）对MT的不同反应有关。

Abstract:

The present study aimed to investigate the effect of melatonin (MT) on lipid metabolism and its effect on lipid metabolism enzymes and factors, and to reveal the mechanism of lipid metabolism in male rats. Twenty SD male rats with similar age and body weight were randomly divided into 2 groups (10 rats per group),which were control group (normal diet, ND) and MT treated group (normal diet with oral melatonin solution, ND+MT). The MT was administrated at 10 mg·kg^-1 BW per day.The experiment lasted for 60 days. At the end of the experiment, blood sample were collected to extract plasma to detect biochemical, hormonal and lipid metabolism related indicators; The rats were sacrificed, the liver and the adipose mass in the abdomen, such as omentum, perirenal fat and epididymal fat was separated and weighed. In additon, liver tissue was sampled for Gene chip and related molecules analysis. The result showed that:1) The liver weight, liver index, omental weight, omental index and epididymal fat weight in ND + MT group were decreased significantly (P<0.05). Low density lipoprotein in serum was significantly decreased (P<0.05), high density lipoprotein and total cholesterol in serum were decreased, while very low density lipoprotein increased.The contents of hepatic long chain fatty acids (LCFA) was significantly decreased (P<0.05). 2) Gene chip and fluorescent quantitative PCR result showed that the mRNA expression of lipolysis related factors and enzymes, such as CPT1(P<0.05) and ALDH3a2 (0.05 < P < 0.1) in liver tissue were increased, while the mRNA expression of fat synthesis related enzyme, such as ACSL3 and FAS was decreased significantly (P<0.05). MT can greatly affect the lipid metabolism with the reduction of visceral fat, its mechanism is connected with the response of hormones and lipid metabolism related enzymes or factors to MT.

中图分类号:

S852.2

闫灵敏, 杨改青, 王林枫, 陈宇, 朱河水, 高腾云, 李明. 褪黑素调节雄性大鼠脂肪代谢的研究[J]. 畜牧兽医学报, 2017, 48(9): 1694-1704.

YAN Ling-min, YANG Gai-qing, WANG Lin-feng, CHEN Yu, ZHU He-shui, GAO Teng-yun, LI Ming. The Study of Melatonin Regulating Lipid Metabolism in Male Rats[J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2017, 48(9): 1694-1704.

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参考文献

[1] MCCORD C P, ALLEN F P. Evidences associating pineal gland function with alterations in pigmentation[J]. J Exp Zool A Ecol Genet Physiol, 1917, 23(1):207-224.
[2] LERNER A B, CASE J D, HEINZELMAN R V. Structure of melatonin[J]. J Am Chem Soc, 1959, 81(22):6084-6085.
[3] JAN J E, REITER R J, WONG P K H, et al. Melatonin has membrane receptor-independent hypnotic action on neurons:an hypothesis[J]. J Pineal Res, 2011, 50(3):233-240.
[4] CAGNACCI A. Influences of melatonin on human orcadian rhythms[J]. Chronobiol Int, 1997, 14(2):205-220.
[5] PANG S F, PANG C S, POON A M S, et al. Melatonin:a chemical photoperiodic signal with clinical significance in humans[J]. Chin Med J, 1998, 111(3):197-203.
[6] BARTNESS T J, DEMAS G E, SONG C K. Seasonal changes in adiposity:the roles of the photoperiod, melatonin and other hormones, and sympathetic nervous system[J]. Exp Biol Med, 2002, 227(6):363-376.
[7] 文勇立, 王永, 齐莎日娜, 等. 不同繁殖节律母牦牛冷暖季血浆褪黑激素RP-HPLC测定[J]. 畜牧兽医学报, 2008, 39(3):302-308.
WEN Y L, WANG Y, QI S, et al. Determination of plasma melatonin of female yaks with different reproductive rhythms by reversed-phase high-performance liquid chromatography in warm and cold seasons[J]. Acta Veterinaria et Zootechnica Sinica, 2008, 39(3):302-308. (in Chinese)
[8] RODENBECK A, HUETHER G, RVTHER E, et al. Altered circadian melatonin secretion patterns in relation to sleep in patients with chronic sleep-wake rhythm disorders[J]. J Pineal Res, 1998, 25(4):201-210.
[9] 霍生东, 袁其建, 卢建雄, 等. 褪黑素受体在未妊娠和妊娠牦牛子宫表达的研究[J]. 畜牧兽医学报, 2015, 46(2):239-244.
HUO S D, YUAN Q J, LU J X, et al. Melatonin receptor expression in uterus during pregnancy, nonpregnancy of yak[J]. Acta Veterinaria et Zootechnica Sinica, 2015, 46(2):239-244. (in Chinese)
[10] SCHWIMMER H, MURSU N, HAIM A. Effects of light and melatonin treatment on body temperature and melatonin secretion daily rhythms in a diurnal rodent, the fat sand rat[J]. Chronobiol Int, 2010, 27(7):1401-1419.
[11] 王林枫, 卢德勋, 孙海洲, 等. 褪黑激素对非生绒期内蒙古白绒山羊体成分的影响[J]. 中国畜牧兽医, 2004, 31(11):3-5.
WANG L F, LU D X, SUN H Z, et al. Effect of melatonin on the body composition of inner Mogolia white cashmere goats in telogen abstract[J]. Animal Science Abroad, 2004, 31(11):3-5. (in Chinese)
[12] 杨凌辉, 刘志民, 李文桐, 等. 褪黑素对大鼠腹腔内脂肪组织代谢的影响[J]. 药学服务与研究, 2005, 5(1):23-24.
YANG L H, LIU Z M, LI W T, et al. Effect of melatonin on metabolism of intra-abdominal fat of rat[J]. Pharmaceutical Care and Research, 2005, 5(1):23-24. (in Chinese)
[13] 王林枫, 柳如意, 杨改青, 等. 褪黑素对大鼠生长及脂肪代谢、分配的影响[J]. 动物营养学报, 2015, 27(8):2456-2465.
WANG L F, LIU R Y, YANG G Q, et al. Effects of Melatonin on growth, and lipometabolism and partition of fat in rat[J]. Chinese Journal of Animal Nutrition, 2015, 27(8):2456-2465. (in Chinese)
[14] SANCHEZ-HIDALGO M, LU Z, TAN D X, et al. Melatonin inhibits fatty acid-induced triglyceride accumulation in ROS17/2.8 cells:implications for osteoblast differentiation and osteoporosis[J]. AM J Physiol Regul Integr Comp Physiol, 2007, 292(6):R2208-R2215.
[15] JIN C J, ENGSTLER A J, SELLMANN C, et al. Sodium butyrate protects mice from the development of the early signs of non-alcoholic fatty liver disease:role of melatonin and lipid peroxidation[J]. Br J Nutr, 2016, 116(10):1682-1693.
[16] JIN J X, LEE S, TAWEECHAIPAISANKUL A, et al. Melatonin regulates lipid metabolism in porcine oocytes[J]. J Pineal Res, 2017, 62(2):e12388.
[17] CHEN X, ZHANG C, ZHAO M, et al. Melatonin alleviates lipopolysaccharide-induced hepatic SREBP-1c activation and lipid accumulation in mice[J]. J Pineal Res, 2011, 51(4):416-425.
[18] LIU Y, MEYER C, XU C F, et al. Animal models of chronic liver diseases[J]. Am J Physiol Gastrointest Liver Physiol, 2013, 304(5):G449-G468.
[19] PRATES E G, NUNES J T, PEREIRA R M. A role of lipid metabolism during cumulus-oocyte complex maturation:impact of lipid modulators to improve embryo production[J]. Mediators Inflamm, 2014, 2014:692067.
[20] SUN H, HUANG F F, QU S. Melatonin:a potential intervention for hepatic steatosis[J]. Lipids Health Dis, 2015, 14(1):75.
[21] FAVERO G, STACCHIOTTI A, CASTREZZATI S, et al. Melatonin reduces obesity and restores adipokine patterns and metabolism in obese (ob/ob) mice[J]. Nutr Res, 2015, 35(10):891-900.
[22] LIU Y, MEI W Q, LI Z C, et al. Effect of melatonin on expression of leptin in subcutaneous fat tissue in insulin-resistant rats[J]. Med J Chin PLA, 2014, 39(1):15-19.
[23] PAN M, SONG Y L, XU J M, et al. Melatonin ameliorates nonalcoholic fatty liver induced by high-fat diet in rats[J]. J Pineal Res, 2006, 41(1):79-84.
[24] 郭英振, 姜怀志, 宋先忱, 等. 不同药物处理对辽宁绒山羊血液生理生化指标的影响[J]. 沈阳农业大学学报, 2011, 42(5):578-582.
GUO Y Z, JIANG H Z, SONG X Z, et al. Effect of different drugs on blood physiological and biochemical indexes in Liaoning cashmere goats[J]. Journal of Shenyang Agricultural University, 2011, 42(5):578-582. (in Chinese)
[25] PICCINETTI C C, MIGLIARINI B, OLIVOTTO I, et al. Melatonin and peripheral circuitries:insights on appetite and metabolism in Danio rerio[J]. Zebrafish, 2013, 10(3):275-282.
[26] HAVEL P J. Role of adipose tissue in body-weight regulation:mechanisms regulating leptin production and energy balance[J]. Proc Nutr Soc, 2000, 59(3):359-371.
[27] JOHN T M, VISWANATHAN M, GEORGE J C, et al. Influence of chronic melatonin implantation on circulating levels of catecholamines, growth hormone, thyroid hormones, glucose, and free fatty acids in the pigeon[J]. Gen Comp Endocrinol, 1990, 79(2):226-232.
[28] OSWAL A, YEO G. Leptin and the control of body weight:a review of its diverse central targets, signaling mechanisms, and role in the pathogenesis of obesity[J]. Obesity, 2010, 18(2):221-229.
[29] DARDENO T A, CHOU S H, MOON H S, et al. Leptin in human physiology and therapeutics[J]. Front Neuroendocrinol, 2010, 31(3):377-393.
[30] 刘宝凤, 周沙沙, 王景霖, 等. Lep和LEPR基因在不同脂尾型绵羊脂肪组织中的mRNA表达研究[J]. 畜牧兽医学报, 2013, 44(7):1014-1022.
LIU B F, ZHOU S S, WANG J L, et al. Differential expression of Lep and LEPR mRNA in adipose tissues of sheep with divergent fat-tails[J]. Acta Veterinaria et Zootechnica Sinica, 2013, 44(7):1014-1022. (in Chinese)
[31] SUN H, HUANG F F, QU S. Melatonin:a potential intervention for hepatic steatosis[J]. Lipids Health Dis, 2015, 14(1):75.
[32] NIEVA J, SHAFTON A, ALTOBELL L J, et al. Lipid-derived aldehydes accelerate light chain amyloid and amorphous aggregation[J]. Biochemistry, 2008, 47(29):7695-7705.
[33] 刘玉清, 唐兆新, 郭剑英, 等. 褪黑素对内毒素血症山羊肝线粒体功能的影响[J]. 畜牧兽医学报, 2009, 40(5):756-762.
LIU Y Q, TANG Z X, GUO J Y, et al. Effect of melatonin on the function of liver mitochondria in goats with endotoxemia[J]. Acta Veterinaria et Zootechnica Sinica, 2009, 40(5):756-762. (in Chinese)
[34] 周向华, 李经才. 褪黑素抗自由基作用及其机制[J]. 中国药理学通报, 1999, 15(1):24-27.
ZHOU X H, LI J C. Effect of melatonin on free radicals and its mechanism[J]. Chinese Pharmacological Bulletin, 1999, 15(1):24-27. (in Chinese)
[35] 魏婷, 张永煜, 张庆华. 肉毒碱棕榈酰基转移酶1A的研究进展[J]. 生命科学, 2013, 25(6):614-620.
WEI T, ZHANG Y Y, ZHANG Q H. Research advances of carnitine palmitoyltransferase 1A[J]. Chinese Bulletin of Life Science, 2013, 25(6):614-620. (in Chinese)
[36] 岳颖, 刘国华, 郑爱娟, 等. 生长动物脂肪代谢关键酶基因表达调控[J]. 动物营养学报, 2012, 24(2):232-238.
YUE Y, LIU G H, ZHENG A J, et al. Modulating the expression of genes regulating key enzymes for lipid metabolism in growing animals[J]. Chinese Journal of Animal Nutrition, 2012, 24(2):232-238. (in Chinese)
[37] TIAN W X. The control of animal fat level and fatty acid synthase activity[J]. Chem Life, 1994, 14(1):1.
[38] LI M, SHI Y, TIAN W X. Factors influencing the levels of fatty acid synthase complex activity in fowl[J]. IUBMB Life, 1999, 47(1):63-69.
[39] LIZARRAGA D, VINARDELL M P, NOÉ V, et al. A lyophilized red grape pomace containing proanthocyanidin-rich dietary fiber induces genetic and metabolic alterations in colon mucosa of female C57BL/6J mice[J]. J Nutr, 2011, 141(9):1597-1604.
[40] 高峰, 高翔. 褪黑素对脑出血继发脑损伤患者血清MDA、NF-κB、TNF-α及β2-MG水平的影响[J]. 中国生化药物杂志, 2015, 35(6):71-73.
GAO F, GAO X. Effect of melatonin on serum MDA, NF-κB, TNF-α and β2-MG levels in secondary brain damage following intracerebral hemorrhage patients[J]. Chinese Journal of Biochemical Pharmaceutics, 2015, 35(6):71-73. (in Chinese)