Aliskiren prevents and ameliorates metabolic syndrome in fructose-fed rats

Abstract

IntroductionThe renin-angiotensin system plays a major role in the pathogenesis of metabolic syndrome. The objective of this study was to examine the effects of aliskiren, a direct renin inhibitor, on the metabolic syndrome of fructose-fed rats.Material and methodsMale Sprague-Dawley rats were divided into 4 groups (n = 6 for each group). Group Con: rats were fed a standard chow diet for 8 weeks, group Fru: rats were fed a high fructose diet (60% fructose) for 8 weeks, group FruA: rats were fed a high fructose diet and were co-infused with aliskiren (100 mg/kg/day), and group FruB: rats were treated as group Fru, but aliskiren was administered 4 weeks later. Systolic blood pressure (SBP), homeostasis model assessment-insulin resistance (HOMA-IR), and blood profiles were measured.ResultsBy the end of week 4 and 8 of a high fructose diet, SBP had increased significantly from 111 ±5 to 142 ±4 and 139 ±5 mmHg (p < 0.05), respectively. A high fructose diet significantly increased HOMA-IR from baseline (6.15 ±1.59) to 21.25 ±2.08 and 21.28 ±3.1 (p < 0.05) at week 4 and 8, respectively, and significantly induced metabolic syndrome. Concurrent aliskiren treatment prevented the development of hypertension and metabolic syndrome in fructose-fed rats. When fructose-induced hypertension was established, subsequent aliskiren treatment for 4 weeks reversed the elevated SBP and ameliorated metabolic syndrome. There were no significant differences in food, water intake, urine flow or body weight gain among groups.ConclusionsAliskiren not only prevents but also ameliorates metabolic syndrome in fructose-fed rats.

Transient Decrease in Circulatory Testosterone and Homocysteine Precedes the Development of Metabolic Syndrome Features in Fructose-Fed Sprague Dawley Rats

“…Although some of the studies reported role of visceral obesity in fructose-induced insulin resistance, in our study, as we have not observed visceral obesity, contribution of it to the observed insulin resistance in our study might be negligible. Korandji et al [27] reported feeding of 60–65% fructose diet increases fasting plasma glucose after one week, whereas Padiya et al [28] and Chou et al [31] reported the similar observation after 4 to 8 weeks of fructose-feeding. Masterjohn et al [26] and Leibowitz et al [32] reported no effect of fructose-feeding on glucose levels after 5 to 9 weeks of feeding.…”

“…A recent meta-analysis of human studies reported that fructose intake is positively correlated with total cholesterol levels when the daily intake of fructose is more than 100 g per day but not when the intake is less than that, suggesting the critical role of fructose quantity in regulating plasma cholesterol levels [34]. Majority of the studies on SD rats reported no change in plasma total cholesterol levels after fructose-feeding [26, 28], whereas Chou et al showed increased levels after four weeks of fructose-feeding [31]. In contrast to this report, we have not observed any increased total cholesterol after 4 weeks of fructose-feeding, but we observed a small increase in plasma total cholesterol levels at 12 weeks of fructose-feeding but they reached normal levels after 24 weeks.…”

“…In line with observations of Masterjohn et al and Leibowitz et al, we have not observed any change in fasting plasma glucose levels even after 24 weeks of fructose-feeding. Leibowitz et al [32] reported no change in fasting plasma insulin levels after fructose-feeding for 5 weeks, whereas Chou et al [31] reported increased plasma insulin after 4 weeks of fructose-feeding. In support to observations of Leibowitz et al [32], in our study, we have not observed increase in fasting plasma insulin level or insulin AUC after 4 weeks of fructose-feeding but we observed elevated fasting insulin and insulin AUC at 12 weeks of fructose-feeding which worsened after 24 weeks.…”

“…However, in the present study, we did not observe increase in adiposity by fructose-feeding which could be possibly due to strain variation. Majority of studies on fructose-induced MS in SD rats reported no effect of fructose on body weight and visceral obesity [28, 31, 32]. In support to these studies, we have not observed increase in visceral fat by fructose-feeding for 12 and 24 weeks; instead, we observed a transient decrease in visceral fat depots at earlier phase (4 weeks) which was also reported by Masterjohn et al [26] and Korandji et al [27].…”

Aliskiren, the first direct renin inhibitor: assessing a role in pediatric hypertension and kidney diseases

“…This provides the rationale for the use of renin inhibitors for the treatment of hypertension, cardiovascular and kidney diseases. Animal studies revealed that aliskiren has favorable metabolic profile in patient with metabolic syndrome by improving glucose tolerance and insulin sensitivity [29, 30]. …”