title: Sesamin prevents decline in exercise capacity and impairment of skeletal muscle mitochondrial function in mice with high-fat diet-induced diabetes.
abstract: RESULTS
  What is the central question of this study? Our aim was to examine whether sesamin can prevent a decline in exercise capacity in high-fat diet-induced diabetic mice. Our hypothesis was that maintenance of mitochondrial function and attenuation of oxidative stress in the skeletal muscle would contribute to this result. What is the main finding and its importance? The new findings are that sesamin prevents the diabetes-induced decrease in exercise capacity and impairment of mitochondrial function through the inhibition of NAD(P)H oxidase-dependent oxidative stress in the skeletal muscle. Sesamin may be useful as a novel agent for the treatment of diabetes mellitus.
  We previously reported that exercise capacity and skeletal muscle mitochondrial function in diabetic mice were impaired, in association with the activation of NAD(P)H oxidase. It has been reported that sesamin inhibits NAD(P)H oxidase-induced superoxide production. Therefore, we examined whether the antioxidant sesamin could prevent a decline in exercise capacity in mice with high-fat diet (HFD)-induced diabetes. C57BL/6J mice were fed a normal diet (ND) or HFD, then treated or not with sesamin (0.2%) to yield the following four groups: ND, ND+Sesamin, HFD and HFD+Sesamin (n = 10 each). After 8 weeks, body weight, fat weight, blood glucose, insulin, triglyceride, total cholesterol and fatty acid were significantly increased in HFD compared with ND mice. Sesamin prevented the increases in blood insulin and lipid levels in HFD-fed mice, but did not affect the plasma glucose. Exercise capacity determined by treadmill tests was significantly reduced in HFD mice, but almost completely recovered in HFD+Sesamin mice. Citrate synthase activity was significantly decreased in the skeletal muscle of HFD mice, and these decreases were also inhibited by sesamin. Superoxide anion and NAD(P)H oxidase activity were significantly increased in HFD mice compared with the ND mice and were ameliorated by sesamin. Sesamin prevented the decline in exercise capacity in HFD-induced diabetic mice via maintenance of mitochondrial function, fat oxidation and attenuation of oxidative stress in the skeletal muscle. Our data suggest that sesamin may be useful as a novel agent for the treatment of diabetes mellitus.
authors: Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors: Shingo
authors: S
authors: Takada
authors: Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors: Shintaro
authors: S
authors: Kinugawa
authors: Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors: Shouji
authors: S
authors: Matsushima
authors: Institute for Health Care Science, Suntory Wellness Ltd, Osaka, Japan.
authors: Daisuke
authors: D
authors: Takemoto
authors: Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors: Takaaki
authors: T
authors: Furihata
authors: Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors: Wataru
authors: W
authors: Mizushima
authors: Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors: Arata
authors: A
authors: Fukushima
authors: Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors: Takashi
authors: T
authors: Yokota
authors: Institute for Health Care Science, Suntory Wellness Ltd, Osaka, Japan.
authors: Yoshiko
authors: Y
authors: Ono
authors: Institute for Health Care Science, Suntory Wellness Ltd, Osaka, Japan.
authors: Hiroshi
authors: H
authors: Shibata
authors: Department of Sport Education, Hokusho University, Ebetsu, Japan.
authors: Koichi
authors: K
authors: Okita
authors: Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors: Hiroyuki
authors: H
authors: Tsutsui
mesh_terms: D000818:Animals; D001835:Body Weight; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology*; D059305:Diet, High-Fat; D004149:Dioxoles / Q000494:pharmacology*; D017079:Exercise Tolerance; D017705:Lignans / Q000494:pharmacology*; D008297:Male; D008810:Mice, Inbred C57BL; D008931:Mitochondria, Muscle / Q000473:pathology*; D018482:Muscle, Skeletal / Q000503:physiopathology*; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress; D010805:Physical Conditioning, Animal; D013481:Superoxides / Q000378:metabolism
chemical_list: D004149:Dioxoles; D017705:Lignans; D013481:Superoxides; D019255:NADPH Oxidases; C054125:sesamin