Effects of benfluorex on fatty acid and glucose metabolism in isolated rat hepatocytes: from metabolic fluxes to gene expression.
Effects of benfluorex on fatty acid and glucose metabolism in isolated rat hepatocytes: from metabolic fluxes to gene expression.
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苯氟醚对离体大鼠肝细胞脂肪酸和葡萄糖代谢的影响：从代谢通量到基因表达。
DOI：
10.2337/diabetes.51.8.2363
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发表时间：
2002
期刊：
影响因子：
7.7
通讯作者：
J. Pégorier
中科院分区：
文献类型：
--
作者：
C. Kohl;D. Ravel;J. Girard;J. Pégorier
本芴及其两种代谢产物（S 422-1和S 1475-1）对脂肪酸和葡萄糖代谢通量和特定基因表达的影响进行了研究，从24小时禁食大鼠分离的肝细胞。benfluorex和S 422-1（0.1或1 mmol/l）均可降低β-氧化速率和酮生成，而S 1475-1无影响。在相同浓度下，benfluorex和S 422-1比S 1475-1更有效地减少乳酸/丙酮酸的异生作用。Benfluorex在丙酮酸羧化酶（乙酰辅酶A浓度下降45%）和甘油醛-3-磷酸脱氢酶（ATP/ADP和NAD（+）/NADH比值降低）水平上抑制了异生。因此，benfluorex和S 422-1都不能抑制二羟基丙酮的异源生成，但都能刺激甘油的异源生成。在benfluorex或S 422-1（10或100 μ mol/l）存在下培养的肝细胞中，编码脂肪酸氧化（肉毒碱棕榈酰转移酶[CPT] I）、生酮（羟甲基戊二酰辅酶A合酶）和异生（葡萄糖-6-磷酸酶，PEPCK）的酶的基因表达降低，而编码葡萄糖激酶和丙酮酸激酶的mRNA增加。相比之下，Glut-2，酰基辅酶A合成酶，CPT II基因的表达不受本芴或S 422-1。总之，本研究表明，本氟雷司主要通过S422 -1影响肝细胞的基因表达和代谢状态，从而减少肝细胞再生。
The effects of benfluorex and two of its metabolites (S 422-1 and S 1475-1) on fatty acid and glucose metabolic fluxes and specific gene expression were studied in hepatocytes isolated from 24-h fasted rats. Both benfluorex and S 422-1 (0.1 or 1 mmol/l) reduced beta-oxidation rates and ketogenesis, whereas S 1475-1 had no effect. At the same concentration, benfluorex and S 422-1 were more efficient in reducing gluconeogenesis from lactate/pyruvate than S 1475-1. Benfluorex inhibited gluconeogenesis at the level of pyruvate carboxylase (45% fall in acetyl-CoA concentration) and of glyceraldehyde-3-phosphate dehydrogenase (decrease in ATP/ADP and NAD(+)/NADH ratios). Accordingly, neither benfluorex nor S 422-1 inhibited gluconeogenesis from dihydroxyacetone, but both stimulated gluconeogenesis from glycerol. In hepatocytes cultured in the presence of benfluorex or S 422-1 (10 or 100 micromol/l), the expression of genes encoding enzymes of fatty acid oxidation (carnitine palmitoyltransferase [CPT] I), ketogenesis (hydroxymethylglutaryl-CoA synthase), and gluconeogenesis (glucose-6-phosphatase, PEPCK) was decreased, whereas mRNAs encoding glucokinase and pyruvate kinase were increased. By contrast, Glut-2, acyl-CoA synthetase, and CPT II gene expression was not affected by benfluorex or S 422-1. In conclusion, this work suggests that benfluorex mainly via S 422-1 reduces gluconeogenesis by affecting gene expression and metabolic status of hepatocytes.
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影响因子：
56.9
作者：
MCGARRY, JD
通讯作者：
MCGARRY, JD
影响因子：
7.7
作者：
Dobbins, RL;Szczepaniak, LS;McGarry, JD
通讯作者：
McGarry, JD
大鼠18S核糖体核糖核酸基因的核苷酸序列和18S核糖体核糖核酸二级结构的建议。
DOI：
--
发表时间：
1984
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Chan,YL;Gutell,R;Noller,HF;Wool,IG
通讯作者：
Wool,IG
影响因子：
--
作者：
SALORANTA, C;KOIVISTO, V;GROOP, L
通讯作者：
GROOP, L