Nutritional and hormonal regulation of the gene for avian malic enzyme

This paper reviews work from our laboratory on the molecular mechanisms involved in the nutritional and hormonal regulation of avian malic enzyme. The activity of hepatic malic enzyme, one of the set of "lipogenic" enzymes, is high in well-fed chickens and low in starved chickens. In chick embryo hepatocytes in culture, insulin and triiodothyronine (T3) are positive effectors and glucagon, acting via cyclic AMP, is a negative effector. Hormone concentrations in blood are consistent with insulin and T3 playing the major positive roles, and glucagon a major negative role, in regulating hepatic malic enzyme activity during the transitions between the fed and the starved states. New results indicate that insulin-like growth factor 1 also stimulates accumulation of malic enzyme. Our strategy has been to trace the intracellular signalling pathway from its distal end, altered enzyme activity, towards its proximal end, interaction of humoral factors with their appropriate cellular receptors. Nutrition- and hormone-induced changes in malic enzyme activity are due to altered concentrations of malic enzyme protein which, in turn, are due to altered rates of synthesis of malic enzyme. Synthesis of malic enzyme is controlled by regulating the level of malic enzyme mRNA which, in turn is regulated at initiation of transcription. The next step in this analysis will be to identify cis-acting sequence elements in the malic enzyme gene which bestow upon it a selective response to nutritional state and hormones. We are using transient expression systems and avian retroviral vectors to test the function of cis-acting elements involved in the regulation of transcription.