Abstract
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.
Highlights
Cardiovascular disease is the number one cause of death in the United States, and over 35% of Americans have some form of cardiovascular disease, such as hypertension, atherosclerosis, coronary artery disease, heart attack, or stroke (Lloyd-Jones et al, 2010)
We observed no change in Nuclear factor of activated T-cells 5 (NFAT5) or aldose reductase (AR) expression in the small intestine, pancreas, blood, aorta, and skin following all dietary treatments (Figure 3)
We characterize the kidney medulla, liver, brain, and adipose tissue as being “salt-responsive” tissues exhibiting upregulated NFAT5 and AR expression and uncover that a high fructose diet can lead to enhanced NFAT5 expression in the kidney cortex
Summary
Cardiovascular disease is the number one cause of death in the United States, and over 35% of Americans have some form of cardiovascular disease, such as hypertension, atherosclerosis, coronary artery disease, heart attack, or stroke (Lloyd-Jones et al, 2010). In the current climate of strong debate over the role of salt in affecting one’s risk for developing hypertension, and the lack of information regarding how increased fructose consumption can affect the body, we sought to examine how a high salt and high fructose diet can alter gene expression. Nuclear factor of activated T-cells 5 (NFAT5) and aldose reductase (AR) gene expression have been extensively studied under high salt concentrations in vitro; it is unknown how high dietary salt consumption alters tissue-specific expression of NFAT5 and AR in vivo. It is unknown how high dietary consumption of fructose affects NFAT5 and AR gene expression in vivo. We present the first tissue-wide characterization of NFAT5 and AR gene expression patterns following consumption of increased salt and/or fructose diets
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