Kazuharu Suzuki

Dietary calcium and phosphorus ratio regulates bone mineralization and turnover in vitamin D receptor knockout mice by affecting intestinal calcium and phosphorus absorption

The effects of the dietary Ca and P ratio, independent of any vitamin D effects, on bone mineralization and turnover was examined in 60 VDRKO mice fed different Ca/P ratio diets. High dietary Ca/P ratio promoted bone mineralization and turnover with adequate intestinal Ca and P transports in VDRKO mice.

Effects of Oral Administration of Moringa oleifera Lam on Glucose Tolerance in Goto-Kakizaki and Wistar Rats

Medicinal plants constitute an important source of potential therapeutic agents for diabetes. In the present study, we investigated the effects of Moringa oleifera (MO) Lam, Moringacea, on glucose tolerance in Wistar rats and Goto-Kakizaki (GK) rats, modeled type 2 diabetes. Major polyphenols in MO powder were quercetin glucosides, rutin, kaempferol glycosides and chlorogenic acids by HPLC analysis. As the results of glucose tolerance test, MO significantly decreased the blood glucose at 20, 30, 45and 60 min for GK rats and at 10, 30 and 45 min for Wistar rats (p<0.05) compared to the both controls after glucose administration. The area under the curve of changes in the blood glucose was significantly higher in the GK control group than in the GK plus MO group (p<0.05) in the periods 30–60 min and 60–120 min. Furthermore, MO significantly decreased stomach emptying in GK rats (p<0.05). The results indicated that MO has an ameliorating effect for glucose intolerance, and the effect might be mediated by quercetin-3-glucoside and fiber contents in MO leaf powder. The action of MO was greater in GK rats than in Wistar rats.

Dietary Hesperidin Exerts Hypoglycemic and Hypolipidemic Effects in Streptozotocin-Induced Marginal Type 1 Diabetic Rats

Citrus bioflavonoids may offer some protection against the early stage of diabetes mellitus and the development of complications. We investigated the effect of hesperidin on blood glucose levels, hepatic glucose-regulating enzyme activities, serum insulin and adiponectin levels, serum and hepatic lipid levels, and parameters of bone loss in streptozotocin (STZ)-induced marginal type 1 diabetic rats. Weanling male rats were randomly assigned to experimental 3 groups: a control (C) group, a STZ induced marginal type 1 diabetes (S) group, and a diabetes and hesperidin group, and fed their respective diets for 4 weeks. STZ injection increased blood glucose in rats, but the increase was marginal. Serum and hepatic lipids, serum adiponectin and insulin levels were significantly changed by STZ injection. Dietary hesperidin (10 g/kg diet) decreased blood glucose by altering the activity of glucose-regulating enzymes, and normalized the lipids and adiponectin levels, but did not change bone parameters in the marginal type 1 diabetic rats. Hesperidin showed both hypoglycemic and hypolipidemic effects but did not affect bone tissue and bone metabolic makers in STZ-injected marginal diabetic weanling rats without any body weight loss due to STZ injection.

Severe Iron Deficiency Decreases Both Bone Formation and Bone Resorption in Rats

The purpose of this study was to clarify the manner in which dietary iron deficiency decreased bone mineral density (BMD) in rats. Eighteen 3-wk-old male Wistar rats were divided into 3 groups of 6 rats each. The rats in 2 of the 3 groups had free access to a control diet (C group) or an iron-deficient diet (ID group) for 4 wk. The rats in the third group (PF group) were pair-fed the control diet to the mean intake of the ID group. Compared with the C and PF groups, hematocrit and hemoglobin concentrations were significantly reduced and bone mineral content and BMD of the femur were significantly lower in the ID group. Bone histomorphometric parameters showed that the bone formation rate and osteoclast surface in the lumbar vertebra were significantly reduced in the ID group compared with the C and PF groups. Furthermore, dietary iron deficiency decreased serum 1,25-dihydroxycholecalciferol, insulin-like growth factor-I, and osteocalcin concentrations and urinary excretion of deoxypyridinoline. These results suggest that severe iron deficiency decreases not only bone formation but also bone resorption.

Hypoglycemic and Hypolipidemic Effects of Hesperidin and Cyclodextrin-Clathrated Hesperetin in Goto-Kakizaki Rats with Type 2 Diabetes

We investigated the hypoglycemic and hypolipidemic effects of two hesperertin glycosides, namely, hesperidin and cyclodextrin (CD)-clathrated hesperetin, in Goto-Kakizaki (GK) weanling rats with type 2 diabetes. We demonstrated that hesperidin and CD-hesperetin normalized glucose metabolism by altering the activities of glucose-regulating enzymes and reducing the levels of lipids in the serum and liver of the GK rats. These effects of hesperidin glycosides were partly produced by altering the expression of genes encoding the peroxisome proliferator-activated receptors, 3-hydroxy-3-methyl-glutaryl coenzyme A reductase, and the low-density lipoprotein receptor.

Dietary Iron Deficiency Decreases Serum Osteocalcin Concentration and Bone Mineral Density in Rats

We investigated the effects of dietary iron deficiency on bone metabolism by measuring markers of bone turnover in rats. Twelve 3-week-old male Wistar-strain rats were fed a control diet or an iron-deficient diet for 4 weeks. Dietary iron deficiency decreased hemoglobin concentration and increased heart weight. Serum osteocalcin concentration, bone mineral content, bone mineral density, and mechanical strength of the femur were significantly lower in the iron-deficient group than in the control group. These results suggested that dietary iron deficiency affected bone, which might have been due to a decrease in bone formation in rats.

Effects of dietary phosphorus intake on bone mineralization and calcium absorption in adult female rats.

We investigated the effects of dietary phosphorus (P) intake on the bone mineralization and calcium (Ca) absorption in adult female rats. Fifteen 16-wk-old female Wistar rats were divided into three groups, and respectively fed a low-P diet containing 0.15% P (LP), a control diet containing 0.5% P (C), and a high-P diet containing 1.5% P (HP) for 42 d. The apparent Ca absorption was significantly increased with decreasing dietary P level. The serum parathyroid hormone concentration was significantly lower in the LP group than in the C and HP groups. The serum osteocalcin concentration and urinary excretion of deoxypyridinoline were significantly higher in the HP groups than in the LP and C groups. The bone mineral density of the fifth lumbar vertebra was significantly increased with decreasing dietary P level. These results indicate that the low-P diet increased Ca absorption, this being effective for bone mineralization in adult female rats.

Induction of increased phosphatidylcholine hydroperoxide by an iron-deficient diet in rats

Abstract The effect of iron-deficiency on lipid peroxidation in male and female rats was investigated and an attempt was made to understand the underlying mechanisms based on the changes in lipid hydroperoxide formation and relevant hepatic enzymes. Forty 4-week-old male and female rats were fed either an iron-deficient diet or a control diet for 4 weeks. The amount of iron in the microsome and cytosol of liver cells decreased 84 to 55% in the iron-deficient rats, and the amount of copper increased 222 to 1206% in the subcellular fraction of the males, but it only increased 14 to 43% in the microsome and cytosol fraction in the females. Serum and liver triglycerides, phospholipid, and cholesterol increased in iron-deficient male rats, but in female, only cholesterol slightly increased. Serum and liver phosphatidylcholine hydroperoxide (PCOOH) increased 55% and 61%, respectively in the iron-deficient males, and increased less in the females (26% and 10%, respectively). Increased xanthine oxidase (XOD) activity, decreased superoxide dismutase (SOD) activity, and markedly increased glutathione peroxidase (GSH-Px) activity were observed in the liver of the males. The lower XOD and SOD activities and slightly GSH-Px in the females may explain the difference in production of PCOOH according to sex. The role of copper accumulation in the production of lipid peroxides in iron-deficient rats is discussed.

Distribution and Major Sources of Flavonoid Intakes in the Middle-Aged Japanese Women

We estimated the intake of individual flavonoids in a cross sectional study and clarified the major sources contributing to the flavonoid levels in the middle-aged Japanese women by a 24-h weighed dietary record study. The subjects included in the study were 516 free-living women. Each subject completed a 24-h weighed dietary record and received a health check-up. We used the Functional Food Factor database for estimating the intake of 5 major flavonoid intakes, i.e. flavan-3-ols, isoflavones, flavonols, flavanones and flavones. The mean intake of flavan-3-ols, isoflavones, flavonols, flavanones and flavones was 1277, 216, 58, 31 and 15 µmol/d, respectively. The richest source of flavan-3-ols was green tea. The 3 major food sources of isoflavone were the processed soy foods and those of flavonol were the onion, moroheiya (nalta jute) and Japanese radish leaves. Grapefruit and citrus fruit juices were the major sources of flavanones, and tsurumurasaki (malabar spinach), green pepper and grapefruit were the main sources of flavone. Furthermore, analysis of sub-samples from middle-aged Japanese women indicated that there may be an association between flavonoid intake and the levels of oxidized LDL, which might be related to the incidence of cardiovascular diseases.

Iron deficiency down-regulates the Akt/TSC1-TSC2/mammalian Target of Rapamycin signaling pathway in rats and in COS-1 cells

Iron deficiency (ID) is one of the most commonly known forms of nutritional deficiencies. Low body iron is thought to induce neurologic defects but may also play a protective role against cancer development by cell growth arrest. Thus, ID may affect cellular pathways controlling cell growth and proliferation, the mechanism of which is still not fully understood. The serine/threonine protein kinase Akt and its downstream target, the mammalian Target of Rapamycin (mTOR), is known to play a crucial role in the regulation of cell growth and survival. Therefore, we hypothesized that Akt/mTOR pathway could be influenced by ID. Three-week-old male Wistar-strain rats were divided into 3 groups and the 2 groups had free access to a control diet (C group) or an iron-deficient diet (D group). The third group (PF group) were pair-fed the control diet to the mean intake of the D group. After 4 weeks, rats were killed and their brains were sampled. In separate experiments, COS-1 cells were cultured with or without the iron chelator deferoxamine. Western blots of brain samples and COS-1 lysates were used to analyze the expression and phosphorylation state of Akt, TSC2, mTOR, and S6 kinase proteins implicated in the Akt/mTOR pathway. Using 2 different ID models, we show for the first time that iron deficiency depresses Akt activity in rats and in COS-1 cells, leading to a decrease in mTOR activity.