Obeid O A, Powell-Tuck J, Emery P W
Department of Human Nutrition, St Bartholomew's and London Hospital School of Medicine and Dentistry, UK.
Int J Obes Relat Metab Disord. 2000 Apr;24(4):508-13. doi: 10.1038/sj.ijo.0801189.
To determine the relative rates of glycogenesis and lipogenesis following administration of a test meal in lean and obese Zucker rats.
Nine-week-old lean and obese Zucker rats were fasted overnight, then tube-fed a test meal of balanced composition amounting to 16kJ (lean rats and one group of obese rats) or 24kJ (one group of obese rats) and containing 200 mg 1-(13)C glucose. Immediately after the meal the rats were injected intraperitoneally with 5 mCi of 3H2O and killed 1 h later.
Glycogenesis was calculated from the incorporation of 3H into liver glycogen divided by the specific activity of plasma water. Lipogenesis was calculated similarly from the incorporation of 3H into saponifiable lipids in liver and perirenal adipose tissue. The proportion of glycogen synthesized by the indirect pathway via pyruvate was determined from the ratio of 3H labelling at positions C6 and C2 in the glycogen glucose residues. Glycogen synthesis from glucose was determined from the ratio of 13C enrichment in liver glycogen to that in plasma glucose.
The rate of synthesis of glycogen was considerably lower in the livers of obese rats than those of lean controls, with the larger meal causing a small but significant increase in glycogenesis. The proportion of glycogen synthesized via pyruvate showed a non-significant increase in the obese rats, while the amount of glycogen synthesized from glucose was significantly decreased. Hepatic lipogenic rates were about five times higher in both groups of obese rats than the lean controls. In adipose tissue, lipogenesis per g tissue was slightly reduced in the obese rats, although there was clearly an increase in adipose tissue lipogenic activity per whole animal. The larger meal caused a greater rise in plasma glucose and insulin concentrations but did not affect lipogenic rates, although it did cause a greater suppression of lipolysis, as indicated by a lower plasma glycerol concentration.
Ingested carbohydrate is partitioned predominantly into hepatic fatty acid synthesis in obese Zucker rats. Hepatic glycogen synthesis is suppressed and comes mainly from precursors other than glucose. The suppression of hepatic glycogen synthesis may contribute to the increased energetic efficiency of obese Zucker rats.
确定给瘦型和肥胖型 Zucker 大鼠喂食试验餐之后糖原生成和脂肪生成的相对速率。
将 9 周龄的瘦型和肥胖型 Zucker 大鼠禁食过夜,然后通过管饲给予成分均衡的试验餐,热量为 16kJ(瘦型大鼠和一组肥胖型大鼠)或 24kJ(一组肥胖型大鼠),且含有 200mg 1-(13)C 葡萄糖。餐后立即给大鼠腹腔注射 5mCi 的 3H2O,并在 1 小时后处死。
糖原生成通过 3H 掺入肝糖原的量除以血浆水的比活度来计算。脂肪生成以类似方式通过 3H 掺入肝脏和肾周脂肪组织中可皂化脂质的量来计算。通过丙酮酸间接途径合成的糖原比例由糖原葡萄糖残基中 C6 和 C2 位置的 3H 标记比率确定。由葡萄糖合成糖原通过肝糖原中 13C 富集与血浆葡萄糖中 13C 富集的比率来确定。
肥胖型大鼠肝脏中的糖原合成速率显著低于瘦型对照大鼠,较大剂量的餐食使糖原生成有小幅但显著的增加。通过丙酮酸合成的糖原比例在肥胖型大鼠中呈非显著增加,而由葡萄糖合成的糖原量显著减少。两组肥胖型大鼠的肝脏脂肪生成速率均约为瘦型对照大鼠的五倍。在脂肪组织中,每克组织的脂肪生成在肥胖型大鼠中略有降低,尽管整个动物的脂肪组织脂肪生成活性明显增加。较大剂量的餐食使血糖和胰岛素浓度有更大幅度的升高,但不影响脂肪生成速率,不过它确实导致脂肪分解受到更大抑制,表现为血浆甘油浓度降低。
在肥胖型 Zucker 大鼠中,摄入的碳水化合物主要分配到肝脏脂肪酸合成中。肝糖原合成受到抑制,且主要来自葡萄糖以外的前体物质。肝糖原合成的抑制可能有助于提高肥胖型 Zucker 大鼠的能量利用效率。