Relationship between lipogenesis, ketogenesis, and malonyl-CoA content in isolated hepatocytes from the obese Zucker rat adapted to a high-fat diet.
Relationship between lipogenesis, ketogenesis, and malonyl-CoA content in isolated hepatocytes from the obese Zucker rat adapted to a high-fat diet.
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适应高脂肪饮食的肥胖 Zucker 大鼠分离肝细胞中脂肪生成、生酮作用和丙二酰辅酶 A 含量之间的关系。
DOI：
10.1016/0026-0495(85)90085-x
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
X. le Lièpvre
中科院分区：
文献类型：
--
作者：
M. Malewiak;S. Griglio;X. le Lièpvre
在成年肥胖Zucker大鼠及其瘦的同窝仔的肝细胞中研究了脂肪生成和酮生成与丙二酰辅酶A（CoA）浓度之间的关系，这些大鼠喂食对照低脂饮食或高脂饮食（30%猪油重量）。在对照饮食中，肥胖大鼠的脂肪生成--尽管在1 mmol/L油酸、10− 6 mol/L胰高血糖素或0.1 mmol/L TOFA（一种降血脂药物）存在下受到强烈抑制--仍然比瘦大鼠高15倍。相反，与瘦大鼠相比，在某些条件下（油酸盐+ TOFA）的生酮率并不显著降低（30%）。在适应高脂肪饮食后，脂肪生成在瘦大鼠中被抑制了四倍，在肥胖大鼠中被抑制了九倍;然而，其幅度在后者中仍然显著更高，即接近于在对照喂养的瘦大鼠中测量的值。在瘦和肥胖大鼠中生酮是可比的，并且在1 mmol/L油酸的存在下比0.3 mmol/L油酸高得多，而脂肪生成并不随培养基中油酸浓度的增加而变化。乙酰辅酶A羧化酶活性测定肝匀浆中的肥胖组较高，但逐步抑制油酰辅酶A的浓度增加，无论瘦和肥胖大鼠的饮食，从而显示没有异常的体外反应，这种抑制剂。与控制饮食，肝细胞丙二酰辅酶A水平显着较高的肥胖大鼠，无论是在基础状态和抑制脂肪生成后，油酸和TOFA。然而，在高脂肪饮食后，基因型之间不再有显著差异。这些结果表明，在肥胖的Zucker大鼠中，生酮依赖于肝细胞丙二酰辅酶A含量，当丙二酰辅酶A降低至瘦的同窝仔中发现的水平时，它们的生酮能力变得“正常化”，就像脂肪喂养后的情况一样。这种正常化的丙二酰辅酶A水平，尽管在肥胖大鼠较高的脂肪生成可能是由于其形成和利用的酶的活性。
The relationship between lipogenesis and ketogenesis and the concentration of malonyl coenzyme A (CoA) was investigated in hepatocytes from adult obese Zucker rats and their lean littermates fed either a control low-fat diet or a high-fat diet (30% lard in weight). With the control diet, lipogenesis—although strongly inhibited in the presence of either 1 mmol/L oleate, 10−6mol/L glucagon or 0.1 mmol/L TOFA (a hypolipidemic drug)—remained about fifteen-fold higher in the obese rats than in the lean rats. In contrast, ketogenesis under some conditions (oleate + TOFA) was not significantly lower (30%) as compared with the lean rats. After adaptation to the high-fat diet, lipogenesis was depressed fourfold in the lean rats and ninefold in the obese ones; however its magnitude remained significantly higher in the latter, namely at a value close to that measured in control-fed lean rats. Ketogenesis was comparable in lean and obese rats and much higher in the presence of 1 mmol/L oleate than of 0.3 mmol/L oleate, whereas lipogenesis did not vary with increasing oleate concentration in the medium. Acetyl-CoA carboxylase activity measured in liver homogenates was higher in the obese group, but was stepwise inhibited by increasing concentrations of oleyl-CoA regardless of the diet for both lean and obese rats, thus showing no abnormality of in vitro responsiveness to this inhibitor. With the control diet, hepatocyte malonyl-CoA levels were significantly higher in the obese rats, both in the basal state and after inhibition of lipogenesis by oleate and TOFA. However, after the high-fat diet, there was no longer a significant difference between the genotypes. These results show that in the obese Zucker rats, ketogenesis is dependent on hepatocyte malonyl-CoA content in the sense that their ketogenic capacity becomes “normalized” when malonyl-CoA is decreased to the levels found in the lean littermates, as it is the case after fat-feeding. This normalization of malonyl-CoA levels in spite of higher lipogenesis in the obese rats may result from the activities of enzymes of its formation and utilization.
在与加压素一起孵育的肝细胞中刺激糖酵解和磷酸果糖激酶刺激剂的积累。
DOI：
10.1042/bj1941023
发表时间：
1981
期刊：
The Biochemical journal
影响因子：
--
作者：
Hue,L;VanSchaftingen,E;Blackmore,PF
通讯作者：
Blackmore,PF
瘦和肥胖 Zucker 大鼠肝细胞脂肪酸合成、糖原代谢和糖异生的比较研究。
DOI：
10.1016/0026-0495(81)90037-8
发表时间：
1981
期刊：
Metabolism: clinical and experimental
影响因子：
--
作者：
McCune,SA;Durant,PJ;Jenkins,PA;Harris,RA
通讯作者：
Harris,RA
果糖 2,6-二磷酸发现两年后。
DOI：
10.1042/bj2060001
发表时间：
1982
期刊：
The Biochemical journal
影响因子：
--
作者：
Hers,HG;VanSchaftingen,E
通讯作者：
VanSchaftingen,E