NFAT5 is differentially expressed in Sprague-Dawley rat tissues in response to high salt and high fructose diets

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.

Negative Effects of Chronic High Intake of Fructose on Lung Diseases

“…Studies have demonstrated that fructose can induce the expression of AR in several tissues [ 127 , 128 , 129 ]. In rats fed a diet containing 64% fructose for eight weeks, AR expression was shown to be increased in the stomach, heart, and lungs [ 129 ].…”

“…Studies have demonstrated that fructose can induce the expression of AR in several tissues [ 127 , 128 , 129 ]. In rats fed a diet containing 64% fructose for eight weeks, AR expression was shown to be increased in the stomach, heart, and lungs [ 129 ]. Moreover, in a rat rehydration model, rehydration with 10% ( p / w ) fructose was found to promote kidney injury by activating AR [ 127 ].…”

“… The possible role of chronic intake of fructose on lung injury through regulation of AR and mTORC1: ( A ) AR is an enzyme of the polyol pathway, that is involved in lung damage by promoting immune cell infiltration, inflammation, and fibrosis [ 124 , 125 , 126 ]. Fructose induces AR expression in several tissues [ 127 , 128 , 129 ]. Chronic intake of fructose may regulate the activity of AR in the lung, inducing lung damage through the activation of the inflammation; ( B ) mTORC1 is involved in the development of lung damage; mTORC1 induces extracellular matrix deposition and inflammation in lung epithelial cells [ 136 , 137 , 138 ]; moreover, in PBMCs, mTORC1 induces corticoid resistance, which is a barrier to lung disease treatment [ 139 ].…”

A Role for Both V1a and V2 Receptors in Renal Heat Stress Injury Amplified by Rehydration with Fructose

“…Increased plasma osmolality may also augment fructose production by stimulating the nuclear translocation of NFAT5, which is the main regulator of aldose reductase expression, the limiting enzyme of the polyol pathway [21]. In turn, fructose metabolism by fructokinase overexpression results in a positive feedback upregulation of both fructokinase and aldose reductase, thus amplifying this pathway [5,22].…”