Role of ATP in the inhibition of lipogenesis in fasted animals

Abstract

This study was undertaken to obtain information both in vivo and in vitro on the role of adenosine triphosphate (ATP) in the inhibition of fatty acid synthesis in fasted mice.Fasted mice were injected intravenously with glucose or fructose or intraperitoneally with insulin to increase the supply of endogenous ATP. They then received acetate 1-(14)C, glucose 6-(3)H or fructose U-(14)C intravenously and were killed at various intervals. The controls received the labeled tracers only. The radioactivities of liver and carcass fatty acids were determined.The action of ATP on homogenized livers from fasted mice was also determined.The stimulation of lipogenesis was obtained under all these conditions, but only in animals fasted for 4 hr. Insulin was active only on the extrahepatic tissues. Fructose, as well as glucose, restored hepatic lipogenesis. In vitro, ATP restored lipogenesis by homogenized livers of mice fasted for 4 hr, but it inhibited the fatty acid synthesis by homogenized livers from unfasted mice.The significance of the results is discussed.

The Effect of Chlorpropamide and Phenethylbiguanide on Lipogenesis

“…In accordance with findings already published [15,16], our results have confirmed that a four-hour fast suffices to consider ably lower lipogenesis in the mouse and that essentially normal values may be restored by the addition of insulin. Furthermore, lipogenesis from glucose is more sensitive to fasting than is that from acetate.…”

“…The findings further suggest that ATP of different origin might not be interchangeable, ATP originating from a different source than from the oxidative chain not being utilisable for fatty acid synthesis. Decreased cellular oxidative phosphorylation might be one of the essential causes for the inhibition of lipo genesis which takes place during a short period of fasting, as already described in one of our previous publications [16]. Studies in support of the one or the other of these hypotheses are currently in progress.…”

“…In particu lar, insulin suppresses the inhibition of lipogenesis resulting from fasting [13,16]. This finding prompted us to investigate whether other hypoglycemic agents such as sulfonylureas or biguanides would have an analogous effect on lipid synthesis in the fasted animal.…”

Enigmatic effect of cellular ATP on fatty acid biosynthesis

“…However, this is a long‐term effect resulting from down regulation of lipogenic enzymes as a consequence of inhibition of protein synthesis by cycloheximide. ATP inhibition of fatty acid synthesis was reported previously by Rous et al [26] in studies carried out with liver homogenates. Their findings, however, may not be relevant to the present study because synthesis of fatty acids under their conditions should have consumed rather than produced ATP.…”