O'Brien L J, Levac K D, Nagy L E
Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada N1G 2W1.
J Nutr. 1998 Jun;128(6):927-33. doi: 10.1093/jn/128.6.927.
Very low protein diets result in a desensitization of hepatic cAMP signaling in rats, which is characterized by a loss of cAMP-dependent protein kinase (PKA) activity and type I regulatory subunit (RI). Here we have tested whether more moderate protein restriction (Trial 1) or energy restriction (Trial 2) also modulates hepatic PKA quantity and activity. In trial 1, weanling rats were allowed free access to diets containing normal protein (15%, AL-NP), moderately restricted protein (12.5%, AL-MP) and low protein (7.5%, AL-LP); in trial 2, rats were allowed free access to diet containing 15% (AL-NP) or 0.5% protein (very low protein, AL-VLP) or were energy restricted by pair-feeding a diet isonitrogenous 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 lower (P < 0.05) in AL-LP and AL-VLP, but not in AL-MP or ER-IN, compared with AL-NP. In contrast, there was no effect of diet on RI in the particulate fraction. RII was not changed by moderate and low protein diets in either the cytosol or particulate fraction. However, type II regulatory subunit (RII) was greater in the cytosol of ER-IN and in the particulate fraction of AL-VLP (P < 0.05) compared with AL-NP. Specific activity 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 contrast, 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 restriction lowers PKA activity in the cytosol and particulate fractions, independent of signficant reduction in RI or RII subunits. Taken together, these data indicate that moderate protein and energy restrictions have differential effects on activity and quantity of PKA.
极低蛋白饮食会导致大鼠肝脏cAMP信号脱敏，其特征是cAMP依赖性蛋白激酶（PKA）活性和I型调节亚基（RI）丧失。在此，我们测试了更适度的蛋白质限制（实验1）或能量限制（实验2）是否也会调节肝脏PKA的数量和活性。在实验1中，断奶大鼠可自由进食含正常蛋白质（15%，AL-NP）、适度限制蛋白质（12.5%，AL-MP）和低蛋白质（7.5%，AL-LP）的饮食；在实验2中，大鼠可自由进食含15%（AL-NP）或0.5%蛋白质（极低蛋白，AL-VLP）的饮食，或通过对喂与AL-NP等氮但能量摄入为其65%的饮食（ER-IN）进行14天的能量限制。与AL-NP组相比，所有限制组在第14天时体重均较低（P<0.05）。与AL-NP相比，AL-LP和AL-VLP组中胞质RI的数量较低（P<0.05），但AL-MP或ER-IN组中则不然。相比之下，饮食对微粒体部分的RI没有影响。中等和低蛋白饮食在胞质或微粒体部分均未改变RII。然而，与AL-NP相比，ER-IN组胞质和AL-VLP组微粒体部分中的II型调节亚基（RII）更多（P<0.05）。与AL-NP组相比，AL-VLP和ER-IN组胞质和微粒体部分中PKA的比活性较低（P<0.05）。相比之下，AL-LP组胞质中PKA的比活性保持不变，但与AL-NP相比，微粒体部分较低（P<0.05）。总之，蛋白质限制饮食会降低胞质中的RI亚基；然而，只有在喂食极低蛋白饮食的大鼠中，RI的这种丧失才与较低的胞质PKA活性相关。相比之下，能量限制会降低胞质和微粒体部分中PKA的活性，而与RI或RII亚基的显著减少无关。综上所述，这些数据表明适度的蛋白质和能量限制对PKA的活性和数量有不同的影响。
