Fructooligosaccharides suppress high-fat diet-induced fat accumulation in C57BL/6J mice.

Two experiments were performed to examine the effects of fructooligosaccharides (FOS) on the development of obesity. In the first experiment, Wistar rats were orally administered a 2.5 g/kg body weight lipid emulsion containing FOS, and the subsequent elevation of plasma triglycerides was significantly suppressed compared with that in rats receiving lipid emulsion alone. In the second experiment, C57BL/6J male mice were fed a high-fat "western" diet with or without 2.5% FOS supplementation (n = 10/group) ad libitum for 12 weeks. Body weight and percent body fat were lower in mice fed FOS than in controls. Furthermore, the weight of the visceral adipose tissue, and the weight and triglyceride content of the liver were significantly lower in the high-fat + FOS group. Fecal excretion of lipids was markedly enhanced by FOS consumption. These results indicate that dietary FOS suppress high-fat diet-induced body fat accumulation, and inhibit intestinal absorption of dietary fat.

Comparison of different sources and degrees of hydrolysis of dietary protein: effect on plasma amino acids, dipeptides, and insulin responses in human subjects.

The effect of protein fractionation on the bioavailability of amino acids and peptides and insulin response and whether the protein source influences these effects in humans are poorly understood. This study compared the effects of different sources and degrees of hydrolysis of dietary protein, independent of carbohydrate, on plasma amino acid and dipeptide levels and insulin responses in humans. Ten subjects were enrolled in the study, with five subjects participating in trials on either soy or whey protein and their hydrolysates. Protein hydrolysates were absorbed more rapidly as plasma amino acids compared to nonhydrolyzed protein. Whey protein also caused more rapid increases in indispensable amino acid and branched-chain amino acid concentrations than soy protein. In addition, protein hydrolysates caused significant increases in Val-Leu and Ile-Leu concentrations compared to nonhydrolyzed protein. Whey protein hydrolysates also induced significantly greater stimulation of insulin release than the other proteins. Taken together, these results demonstrate whey protein hydrolysates cause significantly greater increases in the plasma concentrations of amino acids, dipeptides, and insulin.

Possible involvement of enhanced arginase activity due to up-regulated arginases and decreased hydroxyarginine in accelerating intimal hyperplasia with hyperglycemia.

The present study was designed to investigate the roles of enhanced arginase activity due to up-regulated arginases and the decreased hydroxyarginine for accelerating intimal hyperplasia with hyperglycemia. Thirteen weeks after injection of alloxan or physiological saline, endothelial denudation of the carotid artery was performed to induce intimal hyperplasia. The intimal hyperplasia occurred on 4 weeks following denudation was significantly accelerated by hyperglycemia. The method to measure L-arginine, endogenous NOS inhibitors such as monomethylarginine and asymmetric dimethylarginine, and hydroxyarginine as an intermediate of NO production simultaneously was established with the aid of high-performance liquid chromatography. In hyperglycemia group, the impaired cyclic GMP production as an indicator of NO production in endothelial cells was accompanied by the enhanced arginase activity together with increased expression of arginase I and II proteins, accumulated endogenous NOS inhibitors, reduced concentration of hydroxyarginine, and decreased DDAH activity in endothelial cells. However, NOS activity per se remained unchanged in the hyperglycemia group. Authentic hydroxyarginine inhibited arginase activity in a concentration-dependent manner. The inhibition of arginase with hydroxyarginine at a reduced concentration with hyperglycemia became significantly lower than that for the control. These results suggest that the accelerated intimal hyperplasia with hyperglycemia is closely related to the impaired NO production in endothelial cells, which results from accumulation of endogenous NOS inhibitors and accelerated arginase activity together with up-regulation of arginase I and II proteins. Decreased DDAH activity would bring about the accumulation of endogenous NOS inhibitors. Furthermore, reduced concentration of hydroxyarginine with hyperglycemia possibly results in an enhanced arginase activity in vivo, implicating partly in the impairment of NO production.

Estrogen replacement effectively improves the accelerated intimal hyperplasia following balloon injury of carotid artery in the ovariectomized rats.

Present experiments were designed to investigate the effects of ovariectomy (OVX) and estrogen replacement (ER) on neointimal formation after balloon injury of the rat carotid artery. Young adult female rats were divided into 3 groups of sham operation (control), ovariectomy, and ovariectomy plus estrogen replacement. Estrogen replacement was initiated by implanting a sustained release pellet containing water-soluble 17beta-estradiol 1 week after the ovariectomy. Carotid arteries were harvested 2 weeks after the balloon injury for determinations. The balloon injury caused intimal hyperplasia, which was accompanied by the impaired endothelium-dependent relaxation and cyclic GMP production, and accumulation of asymmetric dimethylarginine (ADMA) as an endogenous NOS inhibitor. Bilateral ovariectomy accelerated the intimal hyperplasia. The acceleration was accompanied by the enhanced impairment of NO production, attenuated reendothelialization, and enhanced accumulation of ADMA. The estrogen replacement improved the accelerated intimal hyperplasia with concomitant improvement of the impaired NO production and accumulated asymmetric dimethylarginine, and facilitated reendothelialization. These results suggests that the enhanced impairment of NO production, which possibly results from the accumulated asymmetric dimethylarginine and lack of reendothelialization, may contribute to the acceleration of intimal hyperplasia by ovariectomy and that estrogen replacement effectively improves the intimal hyperplasia by restoring the impaired NO production through reducing endogenous NOS inhibitor and facilitating reendothelialization.

Accumulated endogenous nitric oxide synthase inhibitors, enhanced arginase activity, attenuated dimethylarginine dimethylaminohydrolase activity and intimal hyperplasia in premenopausal human uterine arteries.

The present study was designed to investigate the involvement of nitric oxide synthase (NOS), endogenous NOS inhibitors, arginase, which shares L-arginine as a common substrate with NOS, and dimethylarginine dimethylaminohydrolase (DDAH) as a metabolizing enzyme of NOS inhibitors in the occurrence of intimal hyperplasia in premenopausal human uterine arteries. Fifty-two uterine arteries were obtained from 52 patients undergoing total hysterectomy with an informed consent for the present study. All specimens were assessed histologically and the intima:media ratio (%) was evaluated as an index of intimal hyperplasia. Nineteen specimens were found to be histologically normal (intima:media ratio=16.1+/-0.8%), whereas remaining 33 specimens were categorized as intimal hyperplasia (intima:media ratio=34.4+/-1.5%). The intimal hyperplasia was associated with the impaired cyclic GMP production without change in endothelial NOS activity per se, accumulation of endogenous NOS inhibitors in endothelial cells, attenuated DDAH activity in endothelial cells and enhanced arginase activity in endothelial cells and smooth muscle layer. These findings suggest that the impaired cyclic GMP production as a marker of NO production is possibly due to the accumulated endogenous NOS inhibitors and enhanced arginase activity, which, in turn, closely relates to the occurrence of intimal hyperplasia, and that the impaired DDAH activity would result in the accumulation of endogenous NOS inhibitors in endothelial cells. Because of the enhanced arginase activity in endothelial cells and smooth muscle layer, the accelerated polyamine biosynthetic pathway may be implicated in the occurrence of intimal hyperplasia in premenopausal human uterine arteries.