Date Published: July 10, 2017
Publisher: Public Library of Science
Author(s): Chu-Lin Chou, Heng Lin, Jin-Shuen Chen, Te-Chao Fang, Michael Bader.
Renin–angiotensin system in visceral fat plays a crucial role in the pathogenesis of metabolic syndrome in fructose-fed rats. However, the effects of renin inhibition on visceral adiposity in metabolic syndrome are not fully investigated. We investigated the effects of renin inhibition on visceral adiposity in fructose-fed rats. Male Wistar–Kyoto rats were divided into 4 groups for 8-week experiments: Group Con (standard chow diet), Group Fru (high-fructose diet; 60% fructose), Group FruA (high-fructose diet and concurrent aliskiren treatment; 100 mg/kg body weight [BW] per day), and Group FruB (high-fructose diet and subsequent, i.e. 4 weeks after initiating high-fructose feeding, aliskiren treatment; 100 mg/kg BW per day). The high-fructose diet induced metabolic syndrome, increased visceral fat weights and adipocyte sizes, and augmented angiotensin II (Ang II), NADPH oxidase (NOX) isoforms expressions, oxidative stress, and dysregulated production of adipocytokines from visceral adipose tissues. Concurrent and subsequent aliskiren administration ameliorated metabolic syndrome, dysregulated adipocytokines, and visceral adiposity in high fructose-fed hypertensive rats, and was associated with reducing Ang II levels, NOX isoforms expressions and oxidative stress in visceral fat tissues. Therefore, this study demonstrates renin inhibition could improve metabolic syndrome, and reduce Ang II levels and oxidative stress in visceral fat tissue in fructose-fed rats, and suggests that visceral adipose Ang II plays a crucial role in the pathogenesis of metabolic syndrome in fructose-fed rats.
The prevalence of metabolic syndrome has increased worldwide, and this increase has been linked to the increased intake of high-fructose corn syrup . Metabolic syndrome, a cluster of conditions including increased blood pressure, elevated blood sugar levels, excess body fat around the waistline, and abnormal cholesterol status, which increases a risk of cardiovascular disease, stroke and diabetes . A high-fructose diet (60% fructose) in rodents has also been reported to cause metabolic disturbances, including elevated blood pressure, glucose intolerance, and hyperlipidemia, as well as a dysregulation of the renin–angiotensin system (RAS) [3, 4].
In this study, our major findings are as follows: First, high-fructose feeding caused systolic hypertension and increased serum glucose, insulin, triglycerides, and total cholesterol levels, consistent with the findings of other [27, 28] and our previous reports [6, 7]. Second, compared with control rats, high-fructose feeding significantly reduced serum and visceral adipose adiponectin levels; increased serum and visceral adipose leptin, resistin, and visfatin levels; increased the visceral fat pad weight and adipocyte size; elevated Ang II and NOX isoforms expressions; and caused oxidative stress (reduced adipose SOD activity and increased adipose lipid peroxide). Third, concurrent and subsequent aliskiren treatments ameliorated SBP, hyperglycemia, and dyslipidemia, as well as increased adipose SOD activity and reduced adipose lipid peroxide and visceral adipose NOX isoforms expressions, and improved dysregulated adipocytokines and adipose hypertrophy. All these data suggest that renin-inhibited pathways have the benefits on improving adipocyte oxidative stress and adiposity with regard to the increased worldwide uptake of high-fructose corn syrup.
Our data suggest that fructose-fed rats exhibit the significant increases in SBP, serum glucose levels, triglyceride levels and total cholesterol levels, visceral adipose Ang II expression, NOX isoforms expressions, oxidative stress, dysregulated adipocytokines, and visceral adiposity. Treatment with the direct renin inhibitor, aliskiren, significantly reduces the increases in SBP, serum glucose levels, triglyceride levels and total cholesterol levels, dysregulated adipocytokines, and visceral adiposity in high fructose-fed hypertensive rats, and is associated with reducing angiotensin II levels, NOX isoforms expressions and oxidative stress in visceral fat tissues.