The fructose-fed rats are an animal model of metabolic syndrome. Recently, role of oxidative stress from adipose tissues has been reported to contribute to fructose-induced hypertension via renin-angiotensin system; however, little is known that the effect of inhibited renin activity on visceral adipose tissues, oxidative stress and aortic vessel of fructose-fed hypertensive rats. This three-year project is to examine the effects of direct renin inhibitor (DRI), on insulin resistance, plasma adipocytokines (adiponectin, leptin, visfatin and resistin), visceral adipose-tissue oxidative stress (peri-kidney fat, omental fat, epididymal fat), and aortic vascular function and remodeling in rats with fructose-induced metabolic syndrome. Male Wistar-Kyoto rats weighing 200 to 230 g will be divided into 4 groups (n=7 for each groups) and conducted for the 8-week course. Group CON: rats will be fed standard chow diet and will be served as the control group; Group Fru: rats will be fed high-fructose diet (60% fructose); Group FruAlis: rats will be fed high-fructose and will be coinfused with aliskiren (100 mg/kg per day) via a subcutaneous osmotic minipump, and Group Fru-Alis: rats will be treated as Group Fru, but aliskiren (100 mg/kg per day) will be administered 4 weeks later. For the first year, the DRI will be demonstrated to prevent and improve insulin resistance, bad adipocytokines, and oxidative stress of visceral adipose tissue. For the second year, the DRI will be proved to prevent and ameliorate oxdative aortic dysfunction and remodeling. For the third year, the DRI will be conducted to investigate how to restore adipose-mediated oxdative stress directly or indirectly via NADPH oxidase activity, nuclear factor kB (NF-kB) and mitogen-activated protein kinase- extracellular signals regulated kinases (MAPK-ERK1/2). The effects of DRI on adipose-mediated oxidative stress will be assessed by serum adipocytokines, serum inflammation cytokines, and the lipid peroxide contents of serum and visceral adipose tissues. Finally, this project will establish the role of inhibited renin activity on visceral adipose tissues, oxidative stress and aortic vascular remodeling in rats with fructose-induced metabolic syndrome.
|Effective start/end date||8/1/14 → 7/31/15|
- adipose tissue
- direct renin inhibitor
- insulin resistance
- metabolic syndrome
- oxidative stress
- vascular remodeling
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