Aki Shinoki

Marginal Zinc Deficiency Exacerbates Experimental Colitis Induced by Dextran Sulfate Sodium in Rats

We investigated the impact of Zn status on the maintenance of mucosal homeostasis. Rats were fed diets containing different amounts of Zn (30, 10, 5, <1 mg Zn/kg diet) for 21 d. Serum Zn concentrations were lower in rats fed marginally Zn-deficient (MZD; 5 mg Zn/kg diet) and severely Zn-deficient (<1 mg/kg) diets but not in those fed the marginally Zn-adequate diet (10 mg/kg) or the Zn-adequate (ZA; 30 mg/kg) group (P < 0.05). However, organ weights, colonic epithelial cell proliferation, and crypt fission did not differ between the MZD and ZA groups. We then evaluated whether MZD modulated dextran sulfate sodium (DSS)-induced colonic inflammation by administering 2% DSS to the MZD and ZA groups for 7 d. Myeloperoxidase activity and TNFα production increased in response to DSS in the MZD group (P < 0.03). Colonic permeability in the 2 groups did not differ after DSS administration. In a culture experiment using isolated mesenteric leukocytes, TNFα production was higher (P < 0.05) and TNF receptor type I (TNFR1) expression was detected in culture medium containing 20 and 30 μmol/L of Zn compared with culture medium lacking Zn supplementation. These results suggest that MZD exacerbated colitis by modulating the immune response through the impairment of TNFα production and TNFR1 expression rather than through the impairment of epithelial barrier function.

Nondigestible Saccharides Suppress the Bacterial Degradation of Quercetin Aglycone in the Large Intestine and Enhance the Bioavailability of Quercetin Glucoside in Rats

Contribution of intestinal bacterial degradation of quercetin aglycone to the promotive effects of fructooligosaccharides and di-D-fructose anhydride III (DFAIII) on quercetin-3-O-beta-glucoside (Q3G) bioavailability was examined. Male Sprague-Dawley rats were fed 0.68% Q3G diets with or without 1.5% or 3% oligosaccharides for 2 weeks. Blood levels and urinary excretion of quercetin and methylquercetin conjugates, measured by methanol extraction and LC-MS analyses, were dose-dependently and adaptively increased by the oligosaccharide supplementation with increasing cecal fermentation (Experiment 1). Degradation of Q3G and quercetin aglycone by cecal bacteria in oligosaccharide-fed rats was much lower than that in the control rats using an anaerobic culture system (Experiment 2). Using the ligated intestinal sacs of anesthetized rats, we found that the cecum possessed high absorptive capacity for quercetin derivatives (Experiment 3). These results demonstrate that feeding of the oligosaccharides strongly suppresses the bacterial degradation of quercetin aglycone in the cecum, thus largely contributing to the increased bioavailability of Q3G.

Ingestion of epilactose, a non-digestible disaccharide, improves postgastrectomy osteopenia and anemia in rats through the promotion of intestinal calcium and iron absorption.

Gastrectomy often results in osteopenia and anemia because of calcium (Ca) and iron (Fe) malabsorption. Here, we investigated the effects of feeding epilactose, a non-digestible disaccharide, on gastrectomy-induced osteopenia, anemia, and Ca and Fe malabsorption in male Sprague-Dawley rats. Totally gastrectomized or sham-operated rats were fed the control or epilactose (50 g/kg) diets for 30 days. Gastrectomy severely decreased intestinal Ca and Fe absorption, femoral bone strength, Ca content, hemoglobin concentration, and hematocrit. These decreases were partly or totally restored by feeding epilactose. Feeding epilactose increased the cecal tissue weight and the soluble Ca concentration and short-chain fatty acid pools of the cecal contents. Collectively, the increases in cecal mucosal area and/or soluble Ca concentration of the cecal contents, resulting from short-chain fatty acid production by intestinal microbes, are thought to be responsible for the epilactose-mediated promotion of Ca and Fe absorption in the gastrectomized rats.

A novel mechanism for the promotion of quercetin glycoside absorption by megalo α-1,6-glucosaccharide in the rat small intestine

The presence of an α-1,6-glucosaccharide enhances absorption of water-soluble quercetin glycosides, a mixture of quercetin-3-O-β-d-glucoside (Q3G, 31.8%), mono (23.3%), di (20.3%) and more d-glucose adducts with α-1,4-linkage to a d-glucose moiety of Q3G, in a ligated small intestinal loop of anesthetized rats. We prepared α-1,6-glucosaccharides with different degrees of polymerization (DP) enzymatically and separated them into a megalo-isomaltosaccharide-containing fraction (M-IM, average DP=11.0) and an oligo-isomaltosaccharide-containing fraction (O-IM, average DP=3.6). Luminal injection of either saccharide fraction promoted the absorption of total quercetin-derivatives from the small intestinal segment and this effect was greater for M-IM than O-IM addition. M-IM also increased Q3G, but not the quercetin aglycone, concentration in the water-phase of the luminal contents more strongly than O-IM. The enhancement of Q3G solubilization in the luminal contents may be responsible for the increases in the quercetin glucoside absorption promoted by α-1,6-glucosaccharides, especially that by M-IM. These results suggest that the ingestion of α-1,6-glucosaccharides promotes Q3G bioavailability.

The Delay in the Development of Experimental Colitis from Isomaltosyloligosaccharides in Rats Is Dependent on the Degree of Polymerization

Background Isomaltosyloligosaccharides (IMO) and dextran (Dex) are hardly digestible in the small intestine and thus influence the luminal environment and affect the maintenance of health. There is wide variation in the degree of polymerization (DP) in Dex and IMO (short-sized IMO, S-IMO; long-sized IMO, L-IMO), and the physiological influence of these compounds may be dependent on their DP. Methodology/Principal Findings Five-week-old male Wistar rats were given a semi-purified diet with or without 30 g/kg diet of the S-IMO (DP = 3.3), L-IMO (DP = 8.4), or Dex (DP = 1230) for two weeks. Dextran sulfate sodium (DSS) was administered to the rats for one week to induce experimental colitis. We evaluated the clinical symptoms during the DSS treatment period by scoring the body weight loss, stool consistency, and rectal bleeding. The development of colitis induced by DSS was delayed in the rats fed S-IMO and Dex diets. The DSS treatment promoted an accumulation of neutrophils in the colonic mucosa in the rats fed the control, S-IMO, and L-IMO diets, as assessed by a measurement of myeloperoxidase (MPO) activity. In contrast, no increase in MPO activity was observed in the Dex-diet-fed rats even with DSS treatment. Immune cell populations in peripheral blood were also modified by the DP of ingested saccharides. Dietary S-IMO increased the concentration of n-butyric acid in the cecal contents and the levels of glucagon-like peptide-2 in the colonic mucosa. Conclusion/Significance Our study provided evidence that the physiological effects of α-glucosaccharides on colitis depend on their DP, linkage type, and digestibility.

Calcium deficiency in the early stages after weaning is associated with the enhancement of a low level of adrenaline-stimulated lipolysis and reduction of adiponectin release in isolated rat mesenteric adipocytes.

Dysregulation of visceral adipocytes increases the incidence of metabolic syndrome. Higher production of nonesterified fatty acid and changes in adipocytokine release may trigger insulin resistance. Many studies have suggested that calcium (Ca) deficiency is associated with insulin resistance; however, the mechanisms are poorly understood. We examined the effects of Ca deficiency on adrenaline-induced lipolysis and adipocytokine release in the early stages after weaning using freshly isolated adipocytes from mesenteric fat tissue of 3-week-old male Sprague-Dawley rats fed a normal-Ca (5 g/kg diet) or low-Ca (1 g/kg diet) diet for 4 weeks. The release rate of nonesterified fatty acid in the mesenteric adipocytes after stimulation with a low level of adrenaline (0.2 microg/mL) was much higher in the Ca-deficient group than in the control group. In contrast, adiponectin release in the mesenteric fat cells was lower in Ca-deficient rats. Leptin and tumor necrosis factor-alpha secretion showed a similar tendency without significant intergroup differences, and monocyte chemoattractant protein-1 release was not affected by Ca deficiency. We found that Ca deficiency reduced the average size of fat cells through a large increase in the number of cells slightly smaller than the average size, which may be associated with the changes in the properties of the mesenteric adipose tissue. Our present results suggest that a low intake of Ca in the early stages after weaning is associated with changes in the properties of mesenteric adipocytes, which may be linked to insulin resistance in the future.

Adrenaline-Induced Lipolysis in Isolated Rat Mesenteric Adipocytes Is Higher in the Large Intestine Than in the Small Intestine

We determined adrenaline-induced lipolysis in mesenteric adipocytes separated from the small and large intestinal parts, because there are large differences in absorbed nutrients and substances between these two intestinal segments. The adrenaline sensitivity was much higher in the mesenteric adipocytes associated with the large intestine without any significant difference in lipolytic capacity. Intestinal bacteria or their metabolites possibly contributed to this phenomenon.