Volpe J J, Marasa J C
Biochim Biophys Acta. 1975 Mar 24;380(3):454-72. doi: 10.1016/0005-2760(75)90113-7.
The major objectives of this study were to define the roles of adrenal glucocorticoids and glucagon in the long-term regulation of fatty acid synthetase and acetyl-CoA carboxylase of mammalian adipose tissue and liver. Particular emphasis was given to elucidation of the mechanisms whereby these hormones produce their regulatory effects on enzymatic activity. To dissociate mental manipulation, nutritional conditions were ridgidly controlled in the experiments described. Administration of glucocorticoids to adult rats led to a marked reductionin activities of fatty acid synthetase and carboxylase in adipose in adipose tissue but no change occurred in liver. Adrenalectomy produced an increase in activities of these lipogenic enzymes in adipose tissure, but, again, no change was noted in liver. The decrease in enzymatic activities in adipose tissue with glucocorticoid administration correlated well with a decrease in fatty acid synthesis, determined in vivo by the 3-H2O method. The mechanisms whereby glucocorticoids led to a decrease in fatty acid synthetase activity were elucidated by the use of immunochemical techniques. Thus, the decrease in fatty acid synthetase activity observed in adipose tissue was shown to reflect a decrease in content of enzyme, and not a change in catalytic efficiency. The mechanism underlying the decrease in enzyme content is a decrease in synthesis of the enzyme. The relation of the effects of glucocorticoids to the effects of certain other hormones involved in regulation of lipogenesis was investigated in hypophysectomized and in diabetic animals. Thus, the observation that the glucocorticoid effect on synthetase and carboxylase occurred in adipose tissue of hypophysectomized rats indicated that alterations in levels of other pituitary-regulated hormones were not necessary for the effect. That glucocorticoids play some role in regulation of synthetase and carboxylase in liver, at lease in the diabetic state, was shown by the observation that the low activities of these enzymes in diabetic animals could be restored to normal by adrenalectomy. An even more pronounced restorative effect was apparent in adipose tissue of adrenalectomized, diabetic animals. Administration of glucagon during the refeeding of starved rats resulted in a marked reduction in the induction of fatty acid synthetase, acetyl-CoA carboxylase and in the rate of incorporation of 3-H from 3-H2O into fatty acids in liver, but no change in these parameters occurred in adipose tissue. Administration of theophylline resulted in intermediate reduction in liver. The mechanisms whereby glucagon led tto a decrease in fatty acid synthetase activity were elucidated by the use of immunochemical techniques. Thus, the changes in fatty acid synthetase activity were shown to reflect reductions in content of enzyme. The mechanism underlying these reductions in content is reduced synthesis of enzyme.
本研究的主要目的是确定肾上腺糖皮质激素和胰高血糖素在哺乳动物脂肪组织和肝脏中脂肪酸合成酶及乙酰辅酶A羧化酶长期调节中的作用。特别强调阐明这些激素对酶活性产生调节作用的机制。为了排除精神因素的干扰，在所描述的实验中严格控制营养条件。给成年大鼠注射糖皮质激素导致脂肪组织中脂肪酸合成酶和羧化酶的活性显著降低，但肝脏中未发生变化。切除肾上腺使脂肪组织中这些生脂酶的活性增加，但肝脏中同样未观察到变化。注射糖皮质激素后脂肪组织中酶活性的降低与用3-H₂O法在体内测定的脂肪酸合成减少密切相关。通过免疫化学技术阐明了糖皮质激素导致脂肪酸合成酶活性降低的机制。因此，脂肪组织中观察到的脂肪酸合成酶活性降低反映了酶含量的减少，而非催化效率的改变。酶含量降低的潜在机制是酶合成减少。在垂体切除的动物和糖尿病动物中研究了糖皮质激素的作用与参与脂肪生成调节的某些其他激素的作用之间的关系。因此，在垂体切除的大鼠脂肪组织中观察到糖皮质激素对合成酶和羧化酶的作用，这表明其他垂体调节激素水平的改变对于该作用并非必需。糖尿病动物中这些酶的低活性可通过肾上腺切除恢复正常，这表明糖皮质激素至少在糖尿病状态下对肝脏中合成酶和羧化酶的调节起一定作用。在肾上腺切除的糖尿病动物的脂肪组织中，这种恢复作用更为明显。饥饿大鼠重新进食期间注射胰高血糖素导致肝脏中脂肪酸合成酶、乙酰辅酶A羧化酶的诱导以及3-H从3-H₂O掺入脂肪酸的速率显著降低，但脂肪组织中这些参数未发生变化。注射茶碱导致肝脏中的降低程度居中。通过免疫化学技术阐明了胰高血糖素导致脂肪酸合成酶活性降低的机制。因此，脂肪酸合成酶活性的变化反映了酶含量的减少。这些含量减少的潜在机制是酶合成减少。
