HEPATIC CCAAT ENHANCER-BINDING PROTEIN (C EBP-ALPHA AND C/EBP-BETA) EXPRESSION CHANGES WITH RIBOFLAVIN DEFICIENCY, DIET RESTRICTION AND STARVATION IN RATS/

To study the role of nuclear regulatory proteins in mediating dietary effects, hepatic CCAAT/enhancer binding protein (C/EBP), mRNA and tran scription rate were measured for C/EBP-alpha and C/EBP-beta in nutriti onal states that profoundly alter energy metabolism and growth. Weanli ng male Sprague-Dawley rats were fed riboflavin-sufficient (R+) or def icient (R-) diets for 4 wk. A diet-restricted, pair-fed (RP) group was maintained concurrently, because riboflavin-deficient rats voluntaril y decrease food consumption by similar to 50% compared with controls. Half of each group was deprived of food for 48 h. The 4-wk treatment a ltered hepatic levels of both proteins (P < 0.05). C/EBP-alpha protein levels were increased similar to twofold by diet restriction. C/EBP-b eta protein levels were increased nearly threefold by riboflavin defic iency. Starvation had no significant effect on the expression of eithe r protein. We investigated the mechanism responsible for increased pro tein by measuring steady-state mRNA levels and transcription rates for C/EBP-alpha and C/EBP-beta. In both isoforms, increases in mRNA were parallel to increases in transcription rates. The nutrient-induced cha nges in protein, mRNA and transcription rates could not be attributed only to alterations in serum glucagon or insulin concentrations. We co nclude that 1) C/EBP-alpha and C/EBP-beta expression responds to diet but may involve different dietary signals for diet restriction vs. rib oflavin deficiency; 2) the dietary regulation of C/EBP-alpha and C/EBP -beta expression seems to be controlled in part at the level of gene t ranscription; and 3) C/EBP-alpha and C/EBP-beta nuclear proteins, by v irtue of their increased quantities, may participate in regulating alt ered energy metabolism and growth by influencing hepatic transcription of key metabolic enzymes.