Gastrectomy (GX) induces osteopenia in rats. The present study examined the skeletal effects of vitamin K₂ in GX rats. Thirty male Sprague-Dawley rats (12 wk old) were randomized by the stratified weight method into the following three groups of 10 animals each: sham operation (control) group; GX group; and GX+oral vitamin K₂ (menatetrenone, 30 mg/kg, 5 d/wk) group. Treatment was initiated at 1 wk after surgery. After 6 wk of treatment, the bone mineral content (BMC), bone mineral density (BMD), and mechanical strength of the femoral diaphysis and distal metaphysis were determined by peripheral quantitative computed tomography and mechanical strength tests, respectively. GX induced decreases in the BMC, BMD, and ultimate force of the femoral diaphysis and distal metaphysis. Vitamin K₂ did not significantly influence the BMC or BMD of the femoral diaphysis or distal metaphysis in GX rats, but attenuated the decrease in the ultimate force and increased the stiffness of the femoral diaphysis. The present study showed that administration of vitamin K₂ to GX rats improved the bone strength of the femoral diaphysis without altering the BMC or BMD, suggesting effects of vitamin K₂ on the cortical bone quality.

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Retinol and its derivative, retinoic acid, have pleiotropic functions including vision, immunity, hematopoiesis, reproduction, cell differentiation/growth, and development. Non-alcoholic fatty liver disease (NAFLD) is one of the most common diseases in developed countries and encompasses a broad spectrum of forms, ranging from steatosis to steatohepatitis, which develops further to cirrhosis. Retinol status has an important role in liver homeostasis. The purpose of this study was to evaluate the retinol status and expression of retinol-related proteins, including enzymes and binding proteins, in methionine-choline deficient (MCD) rats as a model of NAFLD. We examined retinol levels in the plasma and liver and gene expression for β-carotene 15,15′-monooxygenase (BCMO), lecithIn: retinol acyltransferase (LRAT), aldehyde dehydrogenase 1A1 (ALDH1A1), ALDH1A2, and cellular retinol binding protein (CRBP)-I in MCD rats. The plasma retinol levels in MCD rats were lower than those in the controls, whereas hepatic retinol levels in MCD rats were higher. BCMO expression in the intestine and liver in MCD rats was lower, whereas that in the testes and the kidneys was higher than in control rats. Expression of LRAT, CRBP-I, ALDH1A1, and ALDH1A2 in the liver of MCD rats was also higher. Altered expression of retinol-related proteins may affect retinol status in NAFLD.

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Two compounds are known as the vitamin niacIn: nicotinic acid (NiA) and nicotinamide (Nam). The physiological functions and metabolic fates of NiA and Nam are identical, but differ when pharmacological doses are administered. Our study aimed to investigate the metabolic interactions between NiA and Nam when their pharmacological doses were administered together. We measured seven major niacin catabolites, including NiA, Nam, N¹-methylnicotinamide (MNA), N¹-methyl-2-pyridone-5-carboxamide (2-Py), N¹-methyl-4-pyridone-3-carboxamide (4-Py), Nam N-oxide, and nicotinuric acid (NuA). Under physiological conditions, niacin is chiefly catabolized to 4-Py via MNA. However, this was not the primary pathway when rats were fed a diet containing excess niacin. When rats were fed a diet containing excess NiA, NuA was the major catabolite, and on being fed a diet containing excess Nam, MNA was the major catabolite. When rats were fed a diet containing an excess of both NiA and Nam, MNA and NuA were the major catabolites. The metabolic fates of excess NiA and Nam did not mutually interfere. Therefore, the administration of NiA and Nam together may be better than the administration of NiA or Nam alone because different pharmacological effects are expected.

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It has been reported that the enzymic activity of fatty acid synthase (Fas) in rat liver increases during suckling-weaning transition. In this study, we investigated whether induction of the gene (Fasn) in the rat liver during the suckling-weaning transition is regulated by histone acetylation, and the nuclear transcription factors carbohydrate response element-binding protein (ChREBP) and sterol regulatory element-binding protein 1 (SREBP1). We observed that levels of Fas and Fasn increased during suckling-weaning transition. Binding levels of ChREBP and SREBP1 to upstream regions of Fasn increased during the suckling-weaning transition. Acetylation of histones H3 and H4 around Fasn increased during the transient period. Our results suggest that induction of liver Fasn during the suckling-weaning transition is closely associated with increased levels of ChREBP and SREBP1 binding, and acetylation of histones H3 and H4 around the gene.

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Intake of the antioxidant lycopene has been reported to decrease oxidative stress and have beneficial effects on bone health. However, few in vivo studies have addressed these beneficial effects in growing female rodents or young women. The aim of this study was to investigate the effect of lycopene intake on bone metabolism through circulating oxidative stress in growing female rats. Six-week-old Sprague-Dawley female rats were randomly divided into 3 groups according to the lycopene content in their diet: 0, 50, and 100 ppm. The bone mineral density (BMD) of the lumbar spine and the tibial proximal metaphysis increased with lycopene content in a dose-dependent manner; the BMD in 100 ppm group was significantly higher than in the 0 ppm group. The urine deoxypyridinoline concentrations were significantly lower in the 50 and 100 ppm groups than in the 0 ppm group, and the serum bone-type alkaline phosphatase activity was significantly higher in 100 ppm group than in the 0 ppm group. No difference in systemic oxidative stress level was observed; however, the oxidative stress level inversely correlated with the tibial BMD. Our findings suggested that lycopene intake facilitates bone formation and inhibits bone resorption, leading to an increase of BMD in growing female rats.

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Poor growth in utero has been suggested to be associated with adverse levels of serum cholesterol concentrations in later life. In Asia, there have only been a limited number of studies examining the relationship between fetal status and serum lipids, especially in adolescents. The objective of this study was to examine the relationships between birth weight and serum high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol levels; adjusting for current physical status including percent body fat, physical activity and nutrient intake in healthy Japanese late adolescents. The data of 573 late adolescents with an average age of 17.6 (287 boys and 286 girls) who underwent physical examinations which included blood sampling and who had all the required data, were analyzed. Birth weight was obtained from their maternal and child health handbook. Multiple regression analysis showed that birth weight was positively associated with serum HDL in girls, independently of percent body fat or fat intake, when adjusted for current body height and weight. There were no associations between birth weight and serum HDL in boys, or serum LDL in either sex.

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Energy metabolism and substrate oxidation during sleep correlate with sleep stage, suggesting that energy metabolism affects sleep architecture or vice versa. The aim of the present study was to examine whether changes in energy metabolism during sleep, induced by a high-carbohydrate or high-fat meal for dinner, affect sleep architecture. Ten healthy males participated in this study, sleeping 3 nonconsecutive nights in a whole-room calorimeter. The first night was scheduled as an adaptation to the experimental environment. The other 2 nights were experimental calorimetry in a balanced cross-over design with intrasubject comparisons. In each session, subjects comsumed a high carbohydrate (HCD: PFC=10 : 10 : 80) or high fat (HFD: PFC=10 : 78 : 12) meal at 2000 h and slept with a polysomnographic recording in a metabolic chamber for indirect calorimetry (0000 h to 0800 h). Slow wave sleep was decreased during the first sleep cycle and not changed during the second or third sleep cycle under HCD conditions compared with those of HFD. Energy expenditure was not affected by dietary condition but substrate oxidation reflected differences in dietary composition of the dinner during the first and second sleep cycle. The present study suggested the possibility that substrate availability during sleep affects substrate oxidation during sleep, and affects sleep architecture during the first sleep cycle.

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Resveratrol (3,4′,5-trihydroxy-trans-stilbene) is known to enhance the cytotoxicity of the anticancer drug doxorubicin. On the other hand, breast cancer MCF-7 cells acquire resistance to doxorubicin under hypoxic conditions. In this study, we investigated the effect of resveratrol on hypoxia-induced resistance to doxorubicin in MCF-7 cells. Resveratrol and its derivative 3,5-dihydroxy-4′-methoxy-trans-stilbene, but not 3,5-dimethoxy-4′-hydroxy-trans-stilbene, cancelled hypoxia-induced resistance to doxorubicin at a concentration of 10 μM. Carbonyl reductase 1 (CBR1) catalyzes the conversion of doxorubicin to its metabolite doxorubicinol, which is much less effective than doxorubicin. Hypoxia increased the expression of CBR1 at both mRNA and protein levels, and knockdown of CBR1 inhibited hypoxia-induced resistance to doxorubicin in MCF-7 cells. Knockdown of hypoxia-inducible factor (HIF)-1α repressed the hypoxia-induced expression of CBR1. Resveratrol repressed the expression of HIF-1α protein, but not HIF-1α mRNA, and decreased hypoxia-activated HIF-1 activity. Resveratrol repressed the hypoxia-induced expression of CBR1 at both mRNA and protein levels. Likewise, 3,5-dihydroxy-4′-methoxy-trans-stilbene decreased the hypoxia-induced expression of CBR1 protein, but not 3,5-dimethoxy-4′-hydroxy-trans-stilbene. Furthermore, resveratrol decreased the expression of HIF-1α protein even in the presence of the proteasome inhibitor MG132 in hypoxia. Theses results indicate that in MCF-7 cells, HIF-1α-increased CBR1 expression plays an important role in hypoxia-induced resistance to doxorubicin and that resveratrol and 3,5-dihydroxy-4′-methoxy-trans-stilbene decrease CBR1 expression by decreasing HIF-1α protein expression, perhaps through a proteasome-independent pathway, and consequently repress hypoxia-induced resistance to doxorubicin.

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Gly m Bd 28K (Gm28K), a soybean allergen, is formed as a preproprotein consisting of a predicted signal peptide, Gm28K, and the 23-kDa peptide (Gm23K). Gm28K and Gm23K are found in the protein-storage vacuoles (PSVs) of developing soybean seeds. However, the complete structure of Gm28K has not yet been identified and its processing and transport to the vacuoles has never been clarified. In the present study, we elucidated the 5′-nucleotide sequence of cDNA encoding the Gm28K precursor and identified a putative signal peptide (SP) with 24 N-terminal amino acid residues. We expressed peptides from the Gm28K precursor as fusion proteins with enhanced green fluorescent protein (EGFP) in tobacco BY2 suspension-cultured cells. BY2 cells transformed by an expression vector for SP-EGFP-Gm28-Gm23K (SP-EGFP-Gm28-Gm23K/BY2 cells) and SP-Gm28-Gm23K-EGFP/BY2 cells produced the EGFP fused-Gm28K precursor, and the EGFP-fluorescence in their vacuoles were recorded. In the experiments with SP-EGFP/BY2 and SP-EGFP-Gm28K/BY2 cells, large amounts of the EGFP segments were secreted into the medium. On the other hand, the fluorescence of EGFP in SP-EGFP-Gm23K/BY2 cells was shown to accumulate only in the endoplasmic reticulum without secretion into the medium. These findings show that the SP signals the precursor to enter the lumen of the endoplasmic reticulum and that both the Gm28K and Gm23K components may be involved in the transport from the endoplasmic reticulum (ER) lumen via the Golgi to the vacuoles in a proprotein form.

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Oral phosphorus supplementation stimulates fibroblast growth factor 23 (FGF23) secretion; however, the underlying mechanism remains unclear. The aim of this study was to investigate the involvement of parathyroid hormone (PTH) in increased plasma FGF23 levels after oral phosphorus supplementation in rats. Rats received single dose of phosphate with concomitant subcutaneous injection of saline or human PTH (1-34) after treatment with cinacalcet or its vehicle. Cinacalcet is a drug that acts as an allosteric activator of the calcium-sensing receptor and reduces PTH secretion. Plasma phosphorus and PTH levels significantly increased 1 h after oral phosphorus administration and returned to basal levels within 3 h, while plasma FGF23 levels did not change up to 2 h post-treatment, but rather significantly increased at 3 h after administration and maintained higher levels for at least 6 h compared with the 0 time point. Plasma PTH and FGF23 levels were significantly lower in the cinacalcet-treated rats than in the vehicle-treated rats. Plasma phosphorus levels were significantly higher in the cinacalcet-treated rats than in the vehicle-treated rats at 2, 3, 4, and 6 h after oral phosphorus administration. Furthermore, rats treated with cinacalcet+human PTH (1-34) showed transiently but significantly higher plasma FGF23 levels at 3 h after oral phosphorus administration compared with cinacalcet-treated rats. These results suggest that oral phosphorus supplementation secondarily increases circulating FGF23 levels at least partially by stimulation of PTH secretion.

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