Herman Braden A, Ferguson Kaylee M, Fernandez Jared V B, Kauffman Samantha, Spicher Jason T, King Rachel J, Halterman Julia A
Department of Biology, Eastern Mennonite University, Harrisonburg, VA, USA.
Master's in Biomedicine Program, Eastern Mennonite University, Harrisonburg, VA, USA.
Genet Mol Biol. 2019 Apr-Jun;42(2):452-464. doi: 10.1590/1678-4685-gmb-2018-0120. Epub 2019 Feb 28.
Current diets contain an increasing amount of salt and high fructose corn syrup, but it remains unclear as to how dietary salt and fructose affect organ function at the molecular level. This study aimed to test the hypothesis that consumption of high salt and fructose diets would increase tissue-specific expression of two critical osmotically-regulated genes, nuclear factor of activated T-cells 5 (NFAT5) and aldose reductase (AR). Fifty Sprague-Dawley rats were placed on a control, 4% NaCl, 8% NaCl, or 64% fructose diet for eight weeks. Fourteen different tissue samples were harvested and snap-frozen, followed by RNA purification, cDNA synthesis, and NFAT5 and AR gene expression quantification by real-time PCR.Our findings demonstrate that NFAT5 and AR expression are up-regulated in the kidney medulla, liver, brain, and adipose tissue following consumption of a high salt diet. NFAT5 expression is also up-regulated in the kidney cortex following consumption of a 64% fructose diet. These findings highlight the kidney medulla, liver, brain, and adipose tissue as being "salt-responsive" tissues and reveal that a high fructose diet can lead to enhanced NFAT5 expression in the kidney cortex. Further characterization of signaling mechanisms involved could help elucidate how these diets affect organ function long term.
目前的饮食中盐和高果糖玉米糖浆的含量越来越高,但饮食中的盐和果糖如何在分子水平上影响器官功能仍不清楚。本研究旨在验证以下假设:高盐和高果糖饮食会增加两种关键的渗透压调节基因——活化T细胞核因子5(NFAT5)和醛糖还原酶(AR)——的组织特异性表达。将50只Sprague-Dawley大鼠分别置于对照饮食、4%氯化钠饮食、8%氯化钠饮食或64%果糖饮食中喂养8周。采集14种不同的组织样本并速冻,随后进行RNA纯化、cDNA合成,并通过实时PCR对NFAT5和AR基因表达进行定量分析。我们的研究结果表明,食用高盐饮食后,肾髓质、肝脏、大脑和脂肪组织中的NFAT5和AR表达上调。食用64%果糖饮食后,肾皮质中的NFAT5表达也上调。这些发现突出了肾髓质、肝脏、大脑和脂肪组织是“盐反应性”组织,并揭示了高果糖饮食可导致肾皮质中NFAT5表达增强。对相关信号机制的进一步表征有助于阐明这些饮食如何长期影响器官功能。