title: Calorie restriction improves cardiovascular risk factors via reduction of mitochondrial reactive oxygen species in type II diabetic rats.
abstract: Uncoupling protein 2 (UCP2) is an important regulator of intracellular reactive oxygen species (ROS) production. We determined the effects of calorie restriction (CR) on the dynamic aspects of mitochondrial ROS production, UCP2, and the nitric oxide (NO)-cGMP pathway in the cardiovascular tissues of type II diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Some rats were on restricted diets (30% reduction from free intake) from age 29 to 42 weeks. Blood glucose, hemoglobin A1c, plasma levels of free fatty acid, triacylglycerol, and plasminogen activator inhibitor-1 in OLETF rats were significantly higher than those in nondiabetic control [Long-Evans Tokushima Otsuka (LETO)] rats at 29 weeks. Mitochondrial ROS production and UCP2 expression significantly increased in the heart and aorta of OLETF rats compared with those in LETO rats. A fibrogenic growth factor, transforming growth factor (TGF)-beta1 in the coronary vessels, endothelial nitric-oxide synthase, and aortic nitrotyrosine were increased in OLETF rats at 42 weeks. In contrast, an index of the NO-cGMP pathway, phosphorylated vasodilator-stimulated phosphoprotein, and superoxide dismutase activity in the aorta were significantly diminished. The relationship between UCP2 and ROS production in the cardiovascular function of diabetic rats being fed a calorie-restricted diet is unknown. These abnormalities in OLETF rats were reversed to normal levels by CR. CR significantly improved the NO-cGMP pathway via normalizing ROS generation in OLETF rats. A decrease in UCP2 expression by CR may be a compensatory mechanism to counteract decreased intracellular oxidative stress. The data suggest that CR may prevent cardiovascular tissues from oxidative stress provoked by diabetes mellitus.
authors.affiliation: Department of Anti-Aging Food Sciences, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Shikata-cho, Okayama 700-8558, Japan. yukiko-m@md.okayama-u.ac.jp
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Minamiyama
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Bito
authors.forename: Shigekazu
authors.initials: S
authors.lastname: Takemura
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Shintaro
authors.initials: S
authors.lastname: Kodai
authors.forename: Shinjiro
authors.initials: S
authors.lastname: Mizuguchi
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Nishikawa
authors.forename: Shigefumi
authors.initials: S
authors.lastname: Suehiro
authors.forename: Shigeru
authors.initials: S
authors.lastname: Okada
mesh_terms: D000818:Animals; D001835:Body Weight; D031204:Caloric Restriction; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000097:blood; D007473:Ion Channels / Q000235:genetics; D015227:Lipid Peroxidation; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009929:Organ Size; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D051381:Rats; D020318:Rats, Long-Evans; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012307:Risk Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D000071246:Uncoupling Protein 2
chemical_list: D051275:Glucose Transporter Type 4; D007473:Ion Channels; D024101:Mitochondrial Proteins; D017395:Plasminogen Activator Inhibitor 1; D017382:Reactive Oxygen Species; C495694:Slc2a4 protein, rat; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; C002744:3-nitrotyrosine; D014443:Tyrosine; D052250:Nitric Oxide Synthase Type III