Comparative studies on fatty acid synthesis, glycogen metabolism, and gluconeogenesis by hepatocytes isolated from lean and obese Zucker rats.
Comparative studies on fatty acid synthesis, glycogen metabolism, and gluconeogenesis by hepatocytes isolated from lean and obese Zucker rats.
复制标题
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
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发表时间：
1981
期刊：
影响因子：
--
通讯作者：
Harris,RA
中科院分区：
文献类型：
--
作者：
McCune,SA;Durant,PJ;Jenkins,PA;Harris,RA
比较了遗传性肥胖雌性Zucker大鼠和瘦雌性Zucker大鼠的肝细胞。饲喂肥胖大鼠的肝细胞表现出更高的脂肪酸合成率，更广泛的乳酸和丙酮酸从其糖原储存中积累，净葡萄糖利用率增加，但外源脂肪酸产生的酮体更少，柠檬酸水平更低。肥胖大鼠肝细胞的脂肪生成对二丁酰环AMP(DBcAMP)的抑制不敏感，但该核苷酸对两种制剂的糖原分解有相同程度的刺激作用。肥胖大鼠肝细胞的酮体生成对DBcAMP的刺激不太敏感。在培养液中加入乳酸和丙酮酸时，脂肪生成对DBcAMP的敏感性没有差异，这表明肥胖大鼠肝细胞的糖酵解速率较高，这是它们对DBcAMP相对不敏感的原因。DBcAMP在更大程度上提高了肥胖大鼠肝细胞中的柠檬酸水平。饥饿48小时的瘦大鼠制备的肝细胞糖原耗竭，缺乏显着的脂肪生成和糖原合成能力。相比之下，从饥饿肥胖大鼠分离的肝细胞保留了相当数量的肝糖原，并显示出可检测到的脂肪生成和糖原合成的速率。饥饿瘦大鼠制备的肝细胞比饥饿肥胖大鼠制备的肝细胞乳酸糖异生的表观速率更快。因此，肥胖的Zucker大鼠制备的肝细胞比瘦小的大鼠制备的肝细胞更具生糖性、糖酵解性和生脂性，但生酮性和生糖性较低。
Hepatocytes isolated from genetically obese female Zucker rats and lean female Zucker rats were compared. Hepatocytes from fed obese rats exhibited greater rates of fatty acid synthesis, more extensive accumulation of lactate and pyruvate from their glycogen stores, increased rates of net glucose utilization but produced less ketone bodies from exogenous fatty acids and had lower citrate levels than hepatocytes from lean rats. Lipogenesis was not as sensitive to dibutyryl cyclic AMP (DBcAMP) inhibition in hepatocytes from obese rats but glycogenolysis was stimulated to the same extent by this nucleotide in both preparations. Ketogenesis was less sensitive to stimulation by DBcAMP in hepatocytes from obese rats. A difference in sensitivity of lipogenesis to DBcAMP was not found when lactate plus pyruvate was added to the incubation medium, suggesting that a greater rate of glycolysis by hepatocytes from obese rats accounts for their relative insensitivity to DBcAMP. Citrate levels were elevated by DBcAMP to a greater extent in hepatocytes from obese rats. Hepatocytes prepared from lean rats starved for 48 hr were glycogen depleted and lacked significant capacity for lipogenesis and glycogen synthesis. In contrast, hepatocytes isolated from starved obese rats retained considerable amounts of liver glycogen and exhibited detectable rates of lipogenesis and glycogen synthesis. Hepatocytes prepared from starved lean rats gave faster apparent rates of lactate gluconeogenesis than hepatocytes prepared from starved obese rats. Thus, hepatocytes prepared from obese Zucker rats are more glycogenic, glycolytic, and lipogenic but less ketogenic and glucogenic than hepatocytes prepared from lean rats.