Slc35d3参与脂肪、肝脏组织的脂代谢过程
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摘要
目的观察Slc35d3在肥胖小鼠脂肪、肝脏组织中的表达改变,细胞模型中过表达Slc35d3对脂代谢的影响。方法采用real-time PCR的方法检测16周龄的DIO小鼠、ob/ob小鼠、与正常对照组C57/BL6J小鼠的脂肪、肝脏组织中Slc35d3的表达水平。分化六天的3T3-L1细胞电穿孔转染人源的Slc35d3基因,观察对其分化指标及脂代谢相关基因转录水平的影响,同时检测其葡萄糖消耗情况。利用脂质体转染的方法过表达Hep G2细胞中的Slc35d3,转后2天检测脂代谢相关基因的表达;转后48h 1000u M油酸、棕榈酸刺激24h,检测脂代谢相关基因的表达;转后第3天油酸、棕榈酸混合物刺激,第4天恢复正常培养基,检测脂代谢相关基因的表达。结果在DIO小鼠、ob/ob小鼠中,脂肪组织中Slc35d3表达显著低于对照组(P<0.001);肝脏组织中,Slc35d3的表达显著高于对照组(P<0.01)。分化6天的3T3-L1细胞过表达Slc35d3后,分化指标及脂代谢相关基因的表达显著降低,但是葡萄糖消耗没有差异。HepG2细胞过表达Slc35d3后,脂代谢相关基因的表达也显著降低。结论 Slc35d3参与了脂肪及肝脏组织中脂代谢。
Objective The aim of the study was to investigate the changes of Slc35d3 in adipose and liver of obese mice, and the effect of overexpression of Slc35d3 on lipid metabolism in cell models. Methods The relative expression of Slc35d3 in adipose and liver were detected by real-time PCR in 16 weeks DIO, ob/ob and C57/BL6 J mice. Slc35d3 was overexpressed in 3T3-L1 after 6 days differentiation by electroporation, and the expression of the genes related to differentiation and lipid metabolism were detected, as well as glucose consumption. Slc35d3 is overexpressed in Hep G2 with stimulate of FFA( oleate and palmiate), and the expression of the genes related to lipid metabolism were detected. Results The expression of Slc35d3 in adipose of obese mice decreased(P<0.001) whereas increased(P<0.01) in liver of obese mice. With the overexpression of Slc35d3, the genes related to differentiation and lipid metabolism were significantly decreased in 3T3-L1 after 6 days differentiation, but there was no difference in glucose consumption. The expression of the genes related to lipid metabolism were significantly decreased in HepG2 overexpressed Slc35d3. Conclusion Slc35d3 might be involoved in lipid metabolism in adipose and liver.
Objective The aim of the study was to investigate the changes of Slc35d3 in adipose and liver of obese mice, and the effect of overexpression of Slc35d3 on lipid metabolism in cell models. Methods The relative expression of Slc35d3 in adipose and liver were detected by real-time PCR in 16 weeks DIO, ob/ob and C57/BL6 J mice. Slc35d3 was overexpressed in 3T3-L1 after 6 days differentiation by electroporation, and the expression of the genes related to differentiation and lipid metabolism were detected, as well as glucose consumption. Slc35d3 is overexpressed in Hep G2 with stimulate of FFA( oleate and palmiate), and the expression of the genes related to lipid metabolism were detected. Results The expression of Slc35d3 in adipose of obese mice decreased(P<0.001) whereas increased(P<0.01) in liver of obese mice. With the overexpression of Slc35d3, the genes related to differentiation and lipid metabolism were significantly decreased in 3T3-L1 after 6 days differentiation, but there was no difference in glucose consumption. The expression of the genes related to lipid metabolism were significantly decreased in HepG2 overexpressed Slc35d3. Conclusion Slc35d3 might be involoved in lipid metabolism in adipose and liver.
引文
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2.Obesity:preventing and managing the global epidemic.Report of a WHO consultation.World Health Organ Tech Rep Ser.2000,894:p.i-xii,1-253.
3.Chintala S,Tan J,Gautam R,et al.The Slc35d3 gene,encoding an orphan nucleotide sugar transporter,regulates platelet-dense granules.Blood.2007,109(4):p.1533-40.
4.Zhang Z,Hao C,Li C,et al.Mutation of SLC35D3 causes metabolic syndrome by impairing dopamine signaling in striatal D1 neurons.PLo S Genet.2014,10(2):p.e1004124.
5.Ingalls,A M,M M,et al.Obese,a new mutation in the house mouse.J Hered.1950,41(12):p.317-8.
6 .Rink,T J.Genetics.In search of a satiety factor.Nature.1994,372(6505):p.406-7.
7.Zhang Y,Proenca R,Maffei M,et al.Positional cloning of the mouse obese gene and its human homologue.Nature.1994,372(6505):p.425-32.
8.Lobo M,Karsten S,Gray M,et al.FACS-array profiling of striatal projection neuron subtypes in juvenile and adult mouse brains.Nat Neurosci.2006,9(3):p.443-52.
9.Abumrad N,C Coburn,A Ibrahimi.Membrane proteins implicated in long-chain fatty acid uptake by mammalian cells:CD36,FATP and FABPm.Biochim Biophys Acta.1999,1441(1):p.4-13.
10.Drover V,Ajmal M,Nassir F,et al.CD36 deficiency impairs intestinal lipid secretion and clearance of chylomicrons from the blood.J Clin Invest.2005,115(5):p.1290-7.
11 .Imamura M,Inoguchi T,Ikuyama S,et al.ADRP stimulates lipid accumulation and lipid droplet formation in murine fibroblasts.Am J Physiol Endocrinol Metab.2002,283(4):p.E775-83.