Inhibition of hepatic lipogenesis by adenine nucleotides.

Incubation of liver slices and isolated liver cells with adenosine cyclic-3',5'-monophosphate at concentrations which inhibit lipogenesis was found to expand the pool size of the noncyclic adenine nucleotides in the intact cells of the preparations. This observation led to studies which demonstrated that adenosine and adenosine-5'-monophosphate also inhibited lipogenesis and expanded the adenine nucleotide pool size. It is proposed but not proven that the increase in intracellular nucleotides produced by adenosine-5'-monophosphate, adenosine cyclic-3',5'-monophosphate, and adenosine may have an adverse effect upon the synthesis of fatty acids. Because of the expansion of the adenine nucleotide pool size, high concentrations of adenosine cyclic-3',5'-monophosphate should not be used to investigate the mechanism responsible for hormonal regulation of lipogenesis. As an added complication, exogenous adenosine-5'-monophosphate was found to produce a small but significant increase in the intracellular concentration of adenosine cyclic-3',5'-monophosphate of isolated liver cells. This effect also may be a factor in the inhibition of lipogenesis by adenosine-5'-monophosphate. Low concentrations of N6, O2'-dibutyryl adenosine cyclic-3',5'-monophosphate were found to inhibit lipogenesis without increasing the intracellular adenine nucleotide content of either liver slices or isolated liver cells. It is concluded that studies on the mechanism of glucagon regulation of lipogenesis should be carried out with glucagon or low concentrations of N6, O2'-dibutyryl adenosine cyclic-3',5'-monophosphate.