MODERATE DIETARY-PROTEIN AND ENERGY RESTRICTION MODULATE CAMP-DEPENDENT PROTEIN-KINASE ACTIVITY IN RAT-LIVER

Very low protein diets result in a desensitization of hepatic cAMP sig naling in rats, which is characterized by a loss of cAMP-dependent pro tein kinase (PKA) activity and type I regulatory subunit (RI). Here we have tested whether more moderate protein restriction (Trial 1) or en ergy restriction (Trial 2) also modulates hepatic PKA quantity and act ivity. In trial 1, weanling rats were allowed free access to diets con taining normal protein (15%, AL-NP), moderately restricted protein (12 .5%, AL-MP) and low protein (7.5%, AL-LP); in trial 2, rats were allow ed free access to diet containing 15% (AL-NP) or 0.5% protein (very lo w protein, AL-VLP) or were energy restricted by pair-feeding a diet is onitrogenous to AL-NP but at 65% of the energy intake (ER-IN) for 14 d . Body weights were lower (P < 0.05) by d 14 in all restricted groups compared with the AL-NP group. The quantity of cytosolic RI was tower (P < 0.05) in AL-LP and AL-VLP, but not in AL-MP or ER-IN, compared wi th AL-NP. In contrast, there was no effect of diet an RI in the partic ulate fraction. Rtl was not changed by moderate and low protein diets in either the cytosol or particulate fraction. However, type ii regula tory subunit (RID was greater in the cytosol of ER-IN and in the parti culate fraction of AL-VLP (P < 0.05) compared with AL-NP. Specific act ivity of PKA was lower in the cytosol and particulate fraction (P < 0. 05) in the AL-VLP and ER-IN groups compared with the AL-NP group. In c ontrast, specific activity of PKA was maintained in cytosol from AL-LP , but lower in the particulate fraction (P < 0.05) compared with AL-NP , in summary, protein restricted-diets lower RI subunit in the cytosol ; however, only in rats fed very low protein diets is this loss of RI associated with lower cytosolic PKA activity. In contrast, energy rest riction lowers PKA activity in the cytosol and particulate fractions, independent of signficant reduction in RI or RII subunits. Taken toget her, these data indicate that moderate protein and energy restrictions have differential effects on activity and quantity of PKA.