利拉鲁肽对高脂喂养大鼠脂肪组织棕色化基因表达影响的研究
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摘要
目的探讨利拉鲁肽对高脂喂养大鼠棕色脂肪组织(BAT)标志基因及白色脂肪棕色化的影响。方法 40只SD大鼠随机分为正常对照组(Con)、高脂对照组(HF)及利拉鲁肽低、中、高剂量组(Lira-L、Lira-M、Lira-H),每组各8只。各组采用相应干预。12周后留取血清及脂肪组织,检测血清一般生化指标及白色脂肪组织(WAT)、BAT中棕色化基因的表达。结果利拉鲁肽低、中、高剂量组均能上调BAT中解偶联蛋白1(UCP1)等mRNA和蛋白的表达(P<0. 01)。同时,利拉鲁肽低、中、高剂量干预可上调WAT中UCP1等蛋白的表达(P<0. 05)。结论利拉鲁肽可增加高脂喂养大鼠BAT标志基因表达并促进白色脂肪棕色化。
Objective To investigate the effect of Liraglutide on marker gene expression in brown adipose tissue and white adipose browning. Methods Forty male SD rats were divided into normal control group,high-fat control group,low dose Liraglutide group,middle dose Liraglutide group and high dose Liraglutide group. Each group was treated accordingly. At the end of 12 weeks,serum and adipose tissue were collected. Serum biochemical indicators,browning gene expression in white and brown adipose tissue were tested. Results The mRNA expression and protein of UCP1 in brown adipose increased in each Liraglutide group(P<0. 01). At the same time,the protein expression of UCP1 in white adipose tissue increased in each Liraglutide group(P<0. 05). Conclusion Liraglutide intervene could increase marker gene expression in brown adipose tissue and promote white adipose browning.
Objective To investigate the effect of Liraglutide on marker gene expression in brown adipose tissue and white adipose browning. Methods Forty male SD rats were divided into normal control group,high-fat control group,low dose Liraglutide group,middle dose Liraglutide group and high dose Liraglutide group. Each group was treated accordingly. At the end of 12 weeks,serum and adipose tissue were collected. Serum biochemical indicators,browning gene expression in white and brown adipose tissue were tested. Results The mRNA expression and protein of UCP1 in brown adipose increased in each Liraglutide group(P<0. 01). At the same time,the protein expression of UCP1 in white adipose tissue increased in each Liraglutide group(P<0. 05). Conclusion Liraglutide intervene could increase marker gene expression in brown adipose tissue and promote white adipose browning.
引文
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[2]Yang J,Ren J,Song J,et al.Glucagon-like peptide 1 regulates adipogenesis in 3T3-L1 preadipocytes.Int J Mol Med,2013,316:1429-1435.
[3]Chen J,Zhao H,Ma X,et al.GLP-1/GLP-1R signaling in regulation of adipocyte differentiation and lipogenesis.Cell Physiol Biochem,2017,42:1165-1176.
[4]Beiroa D,Imbernon M,Gallego R,et al.GLP-1 agonism stimulates brown adipose tissue thermogenesis and browning through hypothalamic AMPK.Diabetes,2014,63:3346-3358.
[5]Kaineder K,Birngruber T,Rauter G,et al.Chronic intrahypothalamic rather than subcutaneous liraglutide treatment reduces body weight gain and stimulates the melanocortin receptor system.Int JObes(Lond),2017,41:1263-1270.
[6]Campos RMDS,Masquio DCL,Corgosinho FC,et al.Relationship between adiponectin and leptin on osteocalcin in obese adolescents during weight loss therapy.Arch Endocrinol Metab,2018,62:275-284.
[7]Jung S,Han M,Korm S,et al.HDAC6 regulates thermogenesis of brown adipocytes through activating PKA to induce UCP1 expression.Biochem Biophys Res Commun,2018,503:285-290.
[8]Cao X,Zhou X,Liu XM,et al.Liraglutide alters DPP4 in the circumvallate papillae of type 2 diabetic rats.J Mol Endocrinol,2016,57:13-21.
[9]Zheng XB,Ai HY,Yuan SH,et al.Effect of SIRT1 deficiency on function of brown adipose tissue in obese mice.National Med J China,2016,96:1859-1862.
[10]Sakamoto T,Nitta T,Maruno K,et al.Macrophage infiltration into obese adipose tissues suppresses the induction of UCP1 level in mice.Am J Physiol Endocrinol Metab,2016,310:E676-E687.
[11]Levin D,Bell S,Sund R,et al.Pioglitazone and bladder cancer risk:a multipopulation pooled,cumulative exposure analysis.Diabetologia,2015,58:493-504.
[12]Beranger GE,Karbiener M,Barquissau V,et al.In vitro brown and“brite/beige”adipogenesis:human cellular models and molecular aspects.Biochim Biophys Acta,2013,1831:905-914.
[13]Imran KM,Yoon D,Kim YS,et al.A pivotal role of AMPK signaling in medicarpin-mediated formation of brown and beige.Biofactors,2018,44:168-179.
[14]Li X,Wang J,Jiang Z,et al.Role of PRDM16 and its PR domain in the epigenetic regulation of myogenic and adipogenic genes during transdifferentiation of C2C12 cells.Gene,2015,570:191-198.
[15]Cohen P,Levy JD,Zhang Y,et al.Ablation of PRDM16 and beige adipose causes metabolic dysfunction and a subcutaneous to visceral fat switch.Cell,2014,156:304-316.
[16]Aziz SA,Wakeling LA,Miwa S,et al.Metabolic programming of a beige adipocyte phenotype by genistein.Mol Nutr Food Res,2017,61:574.
[17]Cao W,Xu Y,Luo D,et al.Hoxa5 promotes adipose differentiation via increasing DNA methylation level and inhibiting PKA/HSL signal pathway in mice.Cell Physiol Biochem,2018,45:1023-1033.
[18]Zhu Y,Yang R,McLenithan J,et al.Direct conversion of human myoblasts into brown-like adipocytes by engineered super-active PPARγ.Obesity(Silver Spring),2015,23:1014-1021.