Laboratory for Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, University of Belgrade, PO Box 522, 11001 Belgrade, Serbia.
Br J Nutr. 2013 Jun;109(11):1940-8. doi: 10.1017/S0007114512004114. Epub 2012 Oct 16.
Fructose-rich diets (FRD) cause cardiac insulin resistance manifested by impairment of Akt/endothelial NO synthase (eNOS) signalling. In contrast, oestradiol (E2) activates this signalling pathway in the heart. To study the ability of E2 to revert the detrimental effect of fructose on cardiac Akt/eNOS, female rats were subjected to a FRD and ovariectomy followed with or without E2 replacement. We also analysed the effects of the FRD and E2 on cardiac extracellular signal-regulated kinase (Erk 1/2) signalling related to their role in cardiac hypertrophy development. Expression of Akt, eNOS and Erk 1/2, as well as regulatory phosphorylations of these molecules were determined. The protein expression of cardiac Akt and eNOS was not affected by the diet or E2 treatment. However, the FRD was accompanied by a decrease in Akt phosphorylation at Ser(473) and Thr(308), and eNOS at Ser(1177), while the phosphorylation of eNOS at Thr(495) was increased. E2 replacement in ovariectomised fructose-fed rats caused a reversion of the diet effect on Akt and eNOS serine phosphorylation, but mostly had no effect on threonine phosphorylation of the molecules. The FRD and E2 treatment did not influence Erk 1/2 expression and phosphorylation and heart mass as well. The data show that E2 selectively suppress the negative effects of a FRD on Akt/eNOS signalling and probably point to the different effects of E2 on kinase/phosphatase pathways responsible for phosphorylation/dephosphorylation of Akt and eNOS. Furthermore, the results suggest that the heart of females in the reproductive period is partially protected against the damaging effects of increasedfructose intake.
富含果糖的饮食（FRD）会导致心脏胰岛素抵抗，表现为 Akt/内皮型一氧化氮合酶（eNOS）信号转导受损。相比之下，雌激素（E2）会激活心脏中的这条信号通路。为了研究 E2 逆转果糖对心脏 Akt/eNOS 不利影响的能力，雌性大鼠接受 FRD 和卵巢切除术，随后进行或不进行 E2 替代治疗。我们还分析了 FRD 和 E2 对心脏细胞外信号调节激酶（Erk1/2）信号的影响，因为它们与心脏肥大发展有关。测定了 Akt、eNOS 和 Erk1/2 的表达以及这些分子的调节性磷酸化。饮食或 E2 处理并未影响心脏 Akt 和 eNOS 的蛋白表达。然而，FRD 伴随着 Akt 在 Ser(473)和 Thr(308)以及 eNOS 在 Ser(1177)的磷酸化减少，而 eNOS 在 Thr(495)的磷酸化增加。在卵巢切除的果糖喂养大鼠中进行 E2 替代治疗会使饮食对 Akt 和 eNOS 丝氨酸磷酸化的影响发生逆转，但对这些分子的苏氨酸磷酸化的影响主要是没有。FRD 和 E2 处理也不影响 Erk1/2 的表达和磷酸化以及心脏质量。数据表明，E2 选择性地抑制 FRD 对 Akt/eNOS 信号的负面影响，并且可能指向 E2 对负责 Akt 和 eNOS 磷酸化/去磷酸化的激酶/磷酸酶途径的不同影响。此外，结果表明，生殖期女性的心脏对增加果糖摄入的破坏性影响有一定的保护作用。
