Department of Informative Clinical Medicine, Fujita Health University School of Medical Sciences, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake 470-1192, Japan.
Department of Preventive Medical Sciences, Fujita Health University School of Medical Sciences, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake 470-1192, Japan.
Nutrients. 2023 Apr 28;15(9):2122. doi: 10.3390/nu15092122.
We previously reported that maternal fructose consumption increases blood corticosterone levels in rat offspring. However, the underlying mechanism of action remains unclear. In the present study, we aimed to elucidate the molecular mechanism by which maternal high-fructose corn syrup (HFCS) intake increases circulating GC levels in rat offspring (GC; corticosterone in rodents and cortisol in humans). Female Sprague Dawley rats received HFCS solution during gestation and lactation. The male offspring were fed distilled water from weaning to 60 days of age. We investigated the activities of GC-metabolizing enzymes (11β-Hsd1 and 11β-Hsd2) in various tissues (i.e., liver, kidney, adrenal glands, muscle, and white adipose tissue) and epigenetic modification. 11β-Hsd2 activity decreased in the kidney of the HFCS-fed dams. Moreover, the epigenetic analysis suggested that miR-27a reduced mRNA expression in the kidney of offspring. Maternal HFCS-induced elevation of circulating GC levels in offspring may be explained by a decrease in 11β-Hsd2 activity via renal miR-27a expression. The present study may allow us to determine one of the mechanisms of GC elevation in rat offspring that is often observed in the developmental origins of the health and disease (DOHaD) phenomenon.
我们之前曾报道，母体果糖摄入会增加大鼠后代的血液皮质酮水平。然而，其作用机制仍不清楚。在本研究中，我们旨在阐明母体高果糖玉米糖浆（HFCS）摄入如何增加大鼠后代（GC；啮齿动物中的皮质酮和人类中的皮质醇）循环 GC 水平的分子机制。雌性 Sprague Dawley 大鼠在妊娠期和哺乳期接受 HFCS 溶液喂养。雄性后代从断奶到 60 日龄期间喂食蒸馏水。我们研究了 GC 代谢酶（11β-Hsd1 和 11β-Hsd2）在各种组织（即肝脏、肾脏、肾上腺、肌肉和白色脂肪组织）中的活性以及表观遗传修饰。HFCS 喂养的母鼠肾脏中的 11β-Hsd2 活性降低。此外，表观遗传分析表明，miR-27a 降低了后代肾脏中 mRNA 的表达。母体 HFCS 诱导的后代循环 GC 水平升高，可能是通过肾脏中 miR-27a 表达降低 11β-Hsd2 活性来解释的。本研究可能使我们能够确定在发育起源健康与疾病（DOHaD）现象中经常观察到的大鼠后代 GC 升高的机制之一。
