From the Department of Pharmacology (H.Y.S., H.M.C., M.K., I.K.), School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
Cardiovascular Research Institute (H.Y.S., H.M.C., M.K., I.K.), School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
Hypertension. 2019 Sep;74(3):518-525. doi: 10.1161/HYPERTENSIONAHA.119.12941. Epub 2019 Jul 22.
Although maternal high-fructose intake induces cardiometabolic syndrome in adult offspring, whether it induces hypertension in successive multiple generations has not yet been studied. We hypothesized that maternal high-fructose intake induces multigenerational activation of the renin-angiotensin-aldosterone system. Pregnant mice were offered 20% fructose in drinking water, of which subsequent first to fourth generation offspring were raised without being offered fructose. Blood pressure was measured via the tail-cuff method, mRNA expression was determined using the quantitative polymerase chain reaction, and fibrosis was evaluated using trichrome staining. Maternal high-fructose intake statistically significantly increased blood pressure in the first and second, but not the third and fourth, generation offspring as compared to the control group, with maximal increases in serum renin, angiotensin II, and aldosterone in the third generation offspring. It increased the mRNA expression of renin-angiotensin-aldosterone system genes as well as the expression of renin in the kidneys in the first to third generation offspring, with the exception of the vasodilatory Mas1 gene, the mRNA expression of which was the lowest in the second generation offspring. Moreover, it maximally increased fibrosis and the mRNA expression of inflammatory cytokines in the second generation offspring and increased the mRNA expression of oxidative factors in the first to third generation offspring, but maximally decreased the mRNA expression of antioxidant-encoding Sod1 in the second generation offspring. Maternal high-fructose intake induces multigenerational activation of renin-angiotensin-aldosterone system, and the results of this study implicate that it epigenetically induces cardiometabolic syndrome in multiple generations of offspring.
虽然母体高果糖摄入会导致成年后代出现心脏代谢综合征，但它是否会导致连续多代发生高血压尚未得到研究。我们假设母体高果糖摄入会导致肾素-血管紧张素-醛固酮系统的多代激活。给怀孕的老鼠提供 20%的果糖水，其中随后的第一代到第四代后代在没有提供果糖的情况下长大。通过尾套法测量血压，使用定量聚合酶链反应测定 mRNA 表达，并用三染色法评估纤维化。与对照组相比，母体高果糖摄入使第一代和第二代后代的血压明显升高，但在第三代和第四代后代中则没有，其中第三代后代的血清肾素、血管紧张素 II 和醛固酮增加最多。它增加了第一代到第三代后代的肾素-血管紧张素-醛固酮系统基因的 mRNA 表达以及肾脏中的肾素表达，除了血管舒张 Mas1 基因，其在第二代后代中的 mRNA 表达最低。此外，它在第二代后代中最大程度地增加了纤维化和炎症细胞因子的 mRNA 表达，并在第一代到第三代后代中增加了氧化因子的 mRNA 表达，但在第二代后代中最大程度地降低了抗氧化剂编码 Sod1 的 mRNA 表达。母体高果糖摄入会导致肾素-血管紧张素-醛固酮系统的多代激活，本研究的结果表明，它会在后代的多个世代中通过表观遗传方式诱导心脏代谢综合征。
