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The effects of liraglutide on glucose and lipid metabolism, fibroblast growth factor-21 ( FGF-21 )and its receptors (FGFR) in APoE-/-mice with hypoadiponectinemia were investigated.Hypoadiponectinemia facilitated disturbance in glucose and lipid metabolism and insulin resistance. Compared with the control mice, FGF21 mRNA and protein expressions of liver and adipose tissues as well as plasma FGF-21 level were significantly increased in ApoE-/-mice with hypoadiponectinemia, along with lowered expressions of FGFR1 and β-klotho mRNA in adipose tissues, and expressions of FGFR1-3 and β-klotho mRNA in liver. Liraglutide administration improved glucose and lipid metabolism and insulin resistance, and partially reversed the changes of FGF-21 and its receptors induced by hypoadiponectinemia.
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The effects of tumor suppressor in lung cancer-1(TSLC1)upregulation on gene expressions involved in glucose and lipid metabolism in Hepa1-6 cells were investigated.The results showed that TSLC1 overexpression decreased fatty acid synthase and acetyl CoA carboxylase expressions(P<0.05 or P<0.01),increased adipose triglyceride lipase expression(P<0.05),and did not change hormone-sensitive lipase,glucose transporter (GLUT)1,and GLUT4 expressions.These results suggest that TSLC1 overexpression may promote lipolysis and inhibit adipogenesis in liver cells.
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Objective To investigate the effects of high-fat diet induced insulin resistance on fibroblast growth factor-21 (FGF-21) and its receptors expression in ApoE~(-/-) mice. Method Male ApoE~(-/-) mice were randomly divided into normal-chow group(NF,n=20)and high-fat fed group(HF,n=20) and fed for 16 weeks. The insulin sensitivity and glucose-lipid metabolism in awake mice were evaluated by hyperinsulinemic-euglycemic clamp technique combined with 3-[~3H]-glucose as a tracer. The Mrna expressions of FGF-21,β-klotho, and FGFR1-4 were measured by quantitative real-time PCR. FGF-21 protein levels were determined by Western blot. Results Fasting blood glucose, plasma insulin and free fatty acids, triglycerides, free fatty acids, and cholesterols were significantly elevated in HF group compared with NF group(all P<0.01). During the steady-state of clamp, plasma insulin was significantly higher in HF group than that in NF group(P<0.01), and glucose infusion rate was also significantly decreased(P<0.01). At the end of insulin clamp, glucose disappearance rate was significantly lower in HF group than that in NF groups(P<0.01). Hepatic glucose production in NF group was suppressed by 70% ,while in HF group it was suppressed by 51%. The FGF-21 Mrna expressions of hepatic and adipose tissues in HF group were significantly increased compared with NF group(both P<0.01), and β-klotho Mrna expressions increased(P<0. 05). In hepatic and adipose tissues, FGFRI, Mrna expressions were higher in HF group than those in NF group(both P<0.01) ,and FGFR3 Mrna increased(P<0.01 and P<0.05, respectively). In hepatic tissue,FGFR4 Mrna levels were significantly up-regulated in HF group(P<0. 05). Plasma FGF-21 levels were elevated in HF group compared with NF group(P<0.01) ,and FGF-21 protein expressions of hepatic and adipose tissues were also increased(both P<0.05). Conclusion FGF-21, β-klotho, FGFR1, and FGFR3 were significantly up-regulated in ApoE~(-/-) mice fed by high-fat diet, and they might be the targets in regulating glucose-lipid metabolism by FGF-21.
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Objective To observe the effects of JAZF1 (Juxtaposed with another zinc finger gene 1 ) overexpression on glucose and lipid metabolism in 3T3-L1 adipocytes. Methods The tissue distribution of JAZF1 in healthy C57BL/6J mice was detected by real-time quantitative PCR( RT-QPCR). Expression vector for JAZF1 gene was constructed and transfected into 3T3-L1 adipocytes. The mRNA levels of JAZF1, GLUT1, GLUT4, FAS, ACC, SREBP1, ATGL, and HSL implicated in glucose and lipid metabolism were determined by RT-QPCR; JAZF1 protein level was measured by Western blot. Intracelluar lipid accumulation were measured by oil red O staining method. Results In JAZF1-transfected adipocytes, JAZF1 mRNA and protein levels were significantly higher than control cells after 48 h. The mRNA level of HSL was increased significantly (P<0. 05) in JAZF1 transfection group compared with negative control and empty vector group, and the expressions of FAS, ACC, SREBP1 mRNA were decreased significantly(all P<0.01). However, the mRNA levels of ATGL, GLUT1, GLUT4 were not changed. Intracelluar lipid accumulation was decreased significantly (P<0.05 ) by oil red O staining and colorimetric in JAZF1 -transfected cells compared with negative control and empty vector group. Conclusions There was an extensive expression of JAZF1 in various tissues of C57BL/6J mice,indicating that JAZF1 might play a role in maintaining normal physiological function. These results show that overexpression of JAZF1 in 3T3-L1 cells can reduce lipid synthesis, increase lipolysis, and improve lipid accumulation. JAZF1 might provide a new potential therapeutic target for obesity and diabetes.
