Abstract:The aims of this study were to investigate the effects of different folate supplemental levels on the activities of lipoprotein lipase (LPL), fatty acid synthase (FAS) and peroxisome proliferator-activated receptor gamma (PPARγ) content in serum and the expression and methylation of lipid metabolism related genes in liver of broilers. A total of 300 one-day-old Arbor Acres (AA) broilers were randomly allotted to 3 groups with 5 replicates of 20 broilers each. Broilers in control group were fed a basal diet, and broilers in trial groups were fed the basal diet supplemented with 5 and 10 mg/kg folate, respectively. The experiment lasted for 42 days. The results showed as follows: 1) compared with the control group, diet supplemented with 10 mg/kg folate significantly reduced the activity of LPL in serum of 21-day-old broilers (P<0.05); diet supplemented with 5 and 10 mg/kg folate significantly reduced the activity of LPL in serum of 42-day-old broilers (P<0.01), significantly increased the content of PPARγ in serum of 21- and 42-day-old broilers (P<0.01), and significantly reduced the activity of FAS in serum of 21- and 42-day-old broilers (P<0.01). 2) The results of real-time quantitative PCR indicated that the relative expression levels of LPL and PPARγ genes in liver of 42-day-old broilers were not significantly affected by diet supplemented with 5 and 10 mg/kg folate (P>0.05). Compared with the control group, the relative expression levels of FAS gene in liver of 42-day-old broilers was significantly decreased by diet supplemented with 5 and 10 mg/kg folate (P<0.05). 3) The results of methylation analysis showed that the methylation ratios of LPL and PPARγ genes in liver of 42-day-old broilers were not significantly affected by diet supplemented with 5 and 10 mg/kg folate (P>0.05). Compared with the control group, diet supplemented with 5 mg/kg folate significantly improved the methylation ratio of FAS gene in liver of 42-day-old broilers (P<0.01). In conclusion, diet supplemented with 5 and 10 mg/kg folate can significantly decrease serum LPL and FAS activities, significantly increase serum PPARγ content, significantly reduce the expression of FAS gene in liver of 42-day-old broilers. Moreover, diets supplemented with 5 mg/kg folate can also significantly increase the methylation level of FAS gene in liver of 42-day-old broilers.
邢晋祎, 张渝洁, 张宁波, 井文倩, 李珠, 王新正, 徐云超. 叶酸添加水平对肉仔鸡肝脏中脂肪代谢相关基因表达和甲基化的影响[J]. 动物营养学报, 2019, 31(5): 2098-2106.
XING Jinyi, ZHANG Yujie, ZHANG Ningbo, JING Wenqian, LI Zhu, WANG Xinzheng, XU Yunchao. Effects of Folate Supplemental Level on Expression and Methylation of Lipid Metabolism Related Genes in Liver of Broilers. Chinese Journal of Animal Nutrition, 2019, 31(5): 2098-2106.
CRIDER K S,YANG T P,BERRY R J,et al.Folate and DNA methylation:a review of molecular mechanisms and the evidence for folate's role[J].Advances Nutrition,2012,3(1):21-38.
[3]
LUCOCK M.Folic acid:nutritional biochemistry,molecular biology,and role in disease processes[J].Molecular Genetics and Metabolism,2000,71(1/2):121-138.
[4]
NAZKI F H,SAMEER A S,GANAIE B A.Folate:metabolism,genes,polymorphisms and the associated diseases[J].Gene,2014,533(1):11-20.
[8]
SINCLAIR K D,ALLEGRUCCI C,SINGH R,et al.DNA methylation,insulin resistance,and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status[J].Proceedings of the National Academy of Sciences of the United States of America,2007,104(49):19351-19356.
[12]
YANG X,HUANG Y F,SUN C H,et al.Maternal prenatal folic acid supplementation programs offspring lipid metabolism by aberrant dna methylation in hepatic ATGL and adipose LPL in rats[J].Nutrients,2017,9(9):935,doi:10.3390/nu9090935.
[13]
LEE A H,GLIMCHER L H.Intersection of the unfolded protein response and hepatic lipid metabolism[J].Cellular and Molecular Life Sciences,2009,66(17):2835-2850.
[16]
FEOLI-FONSECA J C,LÉVY E,GODARD M,et al.Familial lipoprotein lipase deficiency in infancy:clinical,biochemical,and molecular study[J].The Journal of Pediatrics,1998,133(3):417-423.
[20]
JONES J R,BARRICK C,KIM K A,et al.Deletion of PPAR gamma in adipose tissues of mice protects against high fat diet-induced obesity and insulin resistance[J].Proceedings of the National Academy of Sciences of the United States of America,2005,102(17):6207-6212.
[24]
MULLEN G E,YET L.Progress in the development of fatty acid synthase inhibitors as anticancer targets[J].Bioorganic & Medicinal Chemistry Letters,2015,25(20):4363-4369.
DE-REGIL L M,PEÑA-ROSAS J P,FERNÁNDEZ-GAXIOLA A C,et al.Effects and safety of periconceptional oral folate supplementation for preventing birth defects[J].Cochrane Database of Systematic Reviews,2015,14(12):CD007950.
[19]
MICHALIK L,AUWERX J,BERGER J P,et al.International union of pharmacology.LXI.Peroxisome proliferator-activated receptors[J].Pharmacological Reviews,2006,58(4):726-741.
[23]
YU X Q,LIU R R,ZHAO G P,et al.Folate supplementation modifies CCAAT/enhancer-binding protein α methylation to mediate differentiation of preadipocytes in chickens[J].Poultry Science,2014,93(10):2596-2603.
[6]
LAM T Y,SETO S W,AU A L S,et al.Folic acid supplementation modifies β-adrenoceptor-mediated in vitro lipolysis of obese/diabetic (+db/+db) mice[J].Experimental Biology and Medicine,2009,234(9):1047-1055.
[1]
BILLINGTON C J,Jr,SCHMIDT B,ZHANG L,et al.Maternal diet supplementation with methyl donors and increased parity affect the incidence of craniofacial defects in the offspring of twisted gastrulation mutant mice[J].The Journal of Nutrition,2013,143(3):332-339.
[9]
DOMINGUEZ-SALAS P,MOORE S E,BAKER M S,et al.Maternal nutrition at conception modulates DNA methylation of human metastable epialleles[J].Nature Communication,2014,5:3746.
[11]
TAOUIS M,DRIDI S,CASSY S,et al.Chicken leptin:properties and actions[J].Domestic Animal Endocrinology,2001,21(4):319-327.
[14]
CHMURZYNSKA A,STACHOWIAK M,GAWECKI J,et al.Protein and folic acid content in the maternal diet determine lipid metabolism and response to high-fat feeding in rat progeny in an age-dependent manner[J].Genes & Nutrition,2012,7:223-234.
[17]
LAPERROUSAZ E,MOULLÉ V S,DENIS R G,et al.Lipoprotein lipase in hypothalamus is a key regulator of body weight gain and glucose homeostasis in mice[J].Diabetologia,2017,60(7):1314-1324.
[7]
KUMAR K A,LALITHA A,PAVITHRA D,et al.Maternal dietary folate and/or vitamin B12 restrictions alter body composition (adiposity) and lipid metabolism in Wistar rat offspring[J].Journal of Nutritional Biochemistry,2013,24(1):25-31.
[10]
LAMBROT R,XU C,SAINT-PHAR S,et al.Low paternal dietary folate alters the mouse sperm epigenome and is associated with negative pregnancy outcomes[J].Nature Communication,2013,4(1):2889.
[15]
ZECHNER R,STRAUSS J,FRANK S,et al.The role of lipoprotein lipase in adipose tissue development and metabolism[J].International Journal of Obesity,2000,24(Suppl.4):S53-S56.
[18]
XING J Y,KANG L,JIANG Y L.Effect of dietary betaine supplementation on lipogenesis gene expression and CpG methylation of lipoprotein lipase gene in broilers[J].Molecular Biology Reports,2011,38(3):1975-1981.
SIE K K Y,LI J,LY A,et al.Effect of maternal and postweaning folic acid supplementation on global and gene-specific DNA methylation in the liver of the rat offspring[J].Molecular Nutrition & Food Research,2013,57(4):677-685.