This review assesses the feasibility of using glycemic index (GI) as a predictor of appetite, hunger and satiety by surveying published human intervention studies. We also discuss the relationship between GI and two appetite/satiety control hormones, leptin and ghrelin. Ingestion of high-GI food increased hunger and lowered satiety in short-term human intervention studies. This effect may be attributed to the rapid decline in blood glucose level following a hyperinsulinemic response caused by a sharp and transient increase in blood glucose level that occurs after the ingestion of high-GI food, which is defined as the glucostatic theory. However, appetite, hunger and satiety after the ingestion of foods with varying GI were inconsistent among long-term human intervention studies. From the few relevant long-term studies available, we selected two recent well-designed examples for analysis, but they failed to elicit clear differences in glycemic and insulinemic responses between high- and low-GI meals (consisting of a combination of different foods or key carbohydrate-rich foods incorporated into habitual diets). One of the reasons that these studies could not predict glycemic response to mixed meals is presumably that the GI of each particular food was not reflected in that of the mixed meals as a whole. Thus, it is difficult to conclude that the GI values of foods or mixed meals are a valid long-term predictor for appetite, hunger and satiety. Both insulin and insulin-mediated glucose uptake and metabolism in adipose tissue affect blood leptin concentration and its diurnal pattern. Circulating ghrelin level is suppressed by carbohydrate-rich meals, presumably via glycemia and insulinemia. Accordingly, low-GI foods may not necessarily increase satiety or suppress appetite and/or hunger because of the lack of insulin-mediated leptin stimulation and ghrelin suppression. However, insulin-mediated leptin stimulation and ghrelin suppression per se is not consistent among studies; thus we were not able to identify a clear relationship among GI, satietogenic leptin, and appetitic ghrelin.

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Mild or marginal vitamin A deficiency (MVAD) is still a serious and widespread public health problem in pregnant women and children in developing countries. This study investigated rat lung maturation from prenatal to adult stage during pregnancy and postnatal MVAD and the recovery after postnatal vitamin A supplementation (VAS). Adult female rats and their offspring were randomized into three groups. 1. Control: the mothers and offspring received a normal diet.2. MVAD: The mothers and offspring received a MVAD diet.3. VAS: the mothers received MVAD diet till parturition, and then received the normal diet. The offspring of the VAS group were given low-dose vitamin A from postnatal day 1 to day 7 and received the normal diet after weaning. The lung development, structure, and collagen and elastic fiber of offspring were monitored by morphometric analysis at age 1 d, 2 and 8 wk, respectively. Lower body weight, lung weight, reduced numbers of alveoli and total alveolar surface area as well as increased alveoli septa thickness was observed in MVAD compared to that in the control animals. Increased collagen deposits and decreasing elastic fiber were found in MVAD rats. However, all of these were significantly improved in VAS-treated animals. These data suggest that the rat lung is sensitive to MVAD during the developing stage. Early postnatal vitamin A supplementation can partially restore the normal lung structure.

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Diabetes mellitus is a major endocrine disorder and a growing health problem in most countries which can be ameliorated by numerous bio-molecules such as 1α,25 dihydroxyvitamin D3 [1α,25(OH)2VD3]. With this in mind, the current study investigated the therapeutic and preventive effects of 1α,25(OH)2VD3 on diabetes and its side effects: toxicity in liver, pancreas and kidneys. Our results show that administration of 1α,25(OH)2VD3 in diabetic rats increased the plasmatic insulin level, favored the normal blood glucose levels and normalized the hepatic glycogen concentration. In addition, 1α,25(OH)2VD3 enhanced superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) (by 207, 52 and 72%, respectively) compared to diabetic rats. It also reduced lipid peroxidation and the indices of toxicity in liver and kidneys by significantly decreasing alkaline phosphatases (PAL), aspartate and lactate transaminase (AST and ALT) activities, total and direct bilirubin, triglycerides (TG), cholesterol, creatinine, urea and iron levels in diabetic rats. Moreover, the plasmatic non-enzymatic antioxidant level of HDL-cholesterol, magnesium (Mg), calcium (Ca) and copper (Cu) increased after 1α,25(OH)2VD3 administration. The administration of 1α,25(OH)2VD3 in diabetic rats protects against alloxan-induced histological changes in pancreas. Conclusion: from these data, it is concluded that 1α,25(OH)2VD3 might be useful for the therapy and prevention of diabetes and the numerous side effects especially toxicity in liver, pancreas and kidneys and this protective effect is more obvious in our preventive experiment.

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Reperfusion arrhythmia (RA) is one of the main complications which are also an important cause of sudden cardiac death. The aim of this study was to clarify whether grape seed proanthocyanidins extracts (GSPE) were therapeutic agents against RA. The models of cardiac ischemic reperfusion injury were established in rabbits. GSPE (100 mg/kg, and 250 mg/kg body weight/d, respectively) were administered for 3 wk. The incidence rates of arrhythmias before and after reperfusion of each group were recorded, cardiac infarction area and microstructures of cardiac cells of each rabbit were observed, and the expression of connexin 43 (Cx43) was detected by immunohistochemistry. Data were analyzed using the Leica Qwin V3 image analysis system. Reperfusion induced arrhythmia. Ventricular fibrillation (VF) occurred during the early phase of reperfusion after ischemia. Our results showed that GSPE treatment significantly reduced the incidence of VF and the infarction size compared with the model control group. Moreover, the intercalated disks in the model control group showed collapse, displacement and even the formation of cisterns. After being treated by GSPE, the intercalated disks were improved and there were less collapse and displacement. The expression of Cx43 was improved by GSPE treatment, and high dose of GSPE resulted in significant improvement. The study suggests that GSPE has a protective effect on myocardial ischemic reperfusion arrhythmias, which may be mediated by inhibiting the degradation of Cx43 and enhancing gap junctional conductance.

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We investigated the association between nutrient biomarkers and dietary intake estimated using a brief self-administered dietary history questionnaire (BDHQ) for Japanese children and adolescents. Blood samples were collected from 398 subjects (5th graders of elementary school aged 10-11 y, and 2nd graders of secondary schools aged 13-14 y) randomly selected from among students in Shunan City, Japan, who were then required to answer two questionnaires. Spearman correlations were calculated between dietary intake and the corresponding biomarkers (serum carotenoids, tocopherols, and erythrocyte fatty acids). Correlations with β-carotene and β-cryptoxanthin were significant in the 13- and 14-y age group (r=0.220-0.333, p<0.030) and the 10- and 11-y age subgroup who answered the questionnaire with assistance (r=0.295-0.299, respectively, p=0.006). Consumption of green-yellow vegetables and fruits was significantly correlated with β-carotene and β-cryptoxanthin levels (r=0.205-0.341, p<0.047). In the 13- and 14-y age group, correlations with eicosapentaenoic and docosahexaenoic acids were between 0.215 and 0.473 (p<0.040). Total seafood intake was significantly correlated with marine n-3 polyunsaturated fatty acids (PUFAs; r=0.239-0.420, p<0.023). In the 10- and 11-y age subgroup who completed the questionnaire with assistance, seafood intake was significantly correlated with marine n-3 PUFAs (r=0.239-0.243, p<0.032). In conclusion, dietary intake assessed using the BDHQ reflects the corresponding biomarkers for 13- and 14-y-olds; however, when used for elementary school children, caution is necessary in interpreting the results.

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Mannitol is a six-carbon sugar alcohol that is widely distributed in plants. Sugar alcohols are widely used in various food products because of their numerous beneficial health effects. The present study investigated the effects of mannitol consumption on digestion, large gut fermentation and nutrient metabolism in normal and cecectomized male Wistar rats. After 28 d of feeding with three kinds of diet containing 0, 4 or 8% mannitol, mannitol consumption dose-dependently lowered the digestibilities of crude fat and crude protein, the ratio of body fat accumulation to energy absorbed and the hepatic and serum triglyceride levels in normal rats. After 24 d of feeding with three kinds of diet comprising a control diet, a 5% mannitol-containing diet and a 5% fructooligosaccharides (FOS)-containing diet, mannitol lowered the digestibility of fat and the ratio of body fat accumulation to energy consumed and absorbed in cecectomized rats. On the other hand, FOS consumption had no effect on the accumulation of body fat, but lowered the digestibility of fat. FOS consumption greatly improved the accumulation of body ash in cecectomized rats. These results suggest that mannitol has a lowering effect on body fat accumulation, and further indicate that the cecum is not essential for the appearance of effects of mannitol on digestion, absorption and metabolism.

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Dietary soy protein isolate (SPI) and its undigested high molecular fraction (HMF) exhaustively digested with proteases, compared with casein (CAS), significantly reduced serum and liver cholesterol concentration in rats. Biliary excretion of cholesterol was significantly higher in rats fed SPI and HMF than in those fed CAS. Hepatic expression of ATP-binding cassette transporter G5 (ABCG5) and ATP-binding cassette transporter G8 (ABCG8) mRNA was significantly higher in rats fed SPI and HMF than in those fed CAS. These observations suggest that increased biliary excretion of cholesterol in SPI and HMF groups is caused by the enhanced expression of Abcg5/Abcg8.

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The interaction between causative genes and diet is known to influence the onset of obesity and diabetes in humans, although it has remained difficult to identify diabetogenic gene(s) because humans are genetically and environmentally heterogeneous. Mouse SMXA recombinant inbred (RI) strains are established from parental inbred strains (SM/J and A/J) and have been shown to be beneficial tools for analyzing polygenic traits. We previously mapped a significant quantitative trait locus (QTL, T2dm1sa) on Chromosome (Chr.) 10 and suggestive QTLs on Chr. 2, 6, and 18 for diabetes-related traits by using SMXA RI strains fed a high-carbohydrate diet. As a first step in identifying the responsible gene among QTLs for glucose tolerance mapped on Chr. 10 and 18, we established new strains of A.SM-T2dm1sa and SM.A-D18Mit19-D18Mit7 congenic mice. Each congenic strain bears the diabetogenic allele of an introgressed chromosomal region on a genetic background strain carrying the non-diabetogenic allele. The diabetogenic effect of T2dm1sa mapped on Chr. 10 was not supported by studies of A.SM-T2dm1sa congenic mice when the mice were fed a high-carbohydrate or high-fat diet. SM.A-D18Mit19-D18Mit7 congenic mice showed impaired glucose tolerance not only when they were fed a high-carbohydrate diet, but also when they were fed a high-fat diet. Thus, it appears that gene(s) affecting diabetes-related traits under either dietary condition may be present on Chr. 18.

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It is well known that the collagenolytic cathepsins play an important role in the degradation of bone matrix. Therefore, the purpose of this study was to clarify the prevention effect of bone resorption by milk components. Using double-layer reverse zymography, we found a 20 kDa protein in milk which inhibited cysteine proteases. This inhibitory protein was identified as β-lactoglobulin B. The inhibitory activity of β-lactoglobulin B against cathepsin K was stronger than that of β-lactoglobulin A. β-Lactoglobulin B specifically inhibited papain type cysteine proteases such as cathepsins K and L, but not serine proteases, aspartic proteases or metallo proteases. β-Lactoglobulin B inhibited cathepsin K non-competitively and the Ki value was 10⁻⁵ M. The formation of osteoclastic pits in the culture system was effectively inhibited by 10⁻⁴-10⁻⁵ M β-lactoglobulin B in vitro. Furthermore, we demonstrated that β-lactoglobulin B inhibited degradation of type I-collagen by collagenolytic cathepsins. Using the everted-sac method in rat small intestines, it was found that β-lactoglobulin was more easily absorbed from the intestines of young rats (5 wk-old) than from those of older rats (more than 20 wk-old). The digested products of β-lactoglobulin B with lysyl-endopeptidase showed a similar inhibitory activity against cathepsin K to the intact β-lactoglobulin B did. Therefore, peroral intake of β-lactoglobulin in milk and its digested peptides are expected to help protect osteoclastic bone resorption via inhibition of collagenolytic cathepsins K and L.

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We investigated the suppressive effect of lactic acid bacteria (LAB) isolated from traditional South Asian fermented milk `dahi' on the development of atopic dermatitis (AD) using NC/Nga AD model mice. In the initial evaluation, we confirmed the effect of LAB on serum total IgE using ovalbumin (OVA)-induced type 1 allergy model mice. Forty-one bacterial strains isolated from dahi were evaluated for their ability to induce interleukin (IL)-12 production and suppress IL-4 production in splenocytes obtained from OVA-sensitized mice. Of the 41 strains tested, Lactobacillus delbrueckii subsp. lactis R-037 exhibited the greatest IL-12 induction, suggesting that it is a potent Th1 inducer. Oral administration of heat-treated R-037 significantly suppressed the elevation of serum total IgE in OVA-induced type 1 allergy model mice. In NC/Nga AD model mice, oral administration of heat-treated R-037 reduced inflammatory auricular thickness and alleviated the AD clinical score although the effect on serum total IgE level was unclear. Histopathological findings showed a tendency toward improvement of inflammation. Hyperkeratosis in particular showed improvement in dermatitis skin lesions. These results suggest that oral administration of R-037 may alleviate AD.

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The sum of the urinary excretion of nicotinamide and its catabolites, which are metabolites of NAD and NADP, were observed to have clear diurnal variations in human urine. Then, we examined whether NAD and NADP in blood also showed the diurnal variation. All subjects were housed in the same facility and given the same diet during the experiment. In addition, we examined whether diurnal variations were affected by the intakes of dietary nicotinamide or not. As a result, neither the NAD nor the NADP content of the blood shows the diurnal variation regardless of the administered amount of nicotinamide. The concentrations of NAD and NADP did not increase according to the intake of nicotinamide. The existence of a mechanism by which NAD and the NADP levels of the blood are constantly maintained by the adjustment of the amount of excretion to the urinary bladder, was suggested.

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The acute effects of dihydrocapsaicin (DHC) and capsaicin (CAP) on the number of white blood cells (WBCs), neutrophils, eosinophils, basophils, monocytes, lymphocytes, T lymphocytes, B lymphocytes and NK cells, and serum corticosterone levels were studied in rats. Male 7-wk-old SD rats were divided into DHC (3.0 mg/kg BW), CAP (3.0 mg/kg BW) and control (CON) groups. The number of total WBCs was 1.30-1.42 times significantly higher in the DHC group than in the CON group at 6-12 h. The number of neutrophils was 1.62 times significantly higher in the DHC group than in the CON group at 12 h. The number of total WBCs and neutrophils, however, showed no significant changes between the CAP and CON groups. The number of lymphocytes was 0.61 and 0.70 times significantly lower in the DHC and CAP groups than in the CON group at 3 h. The number of T lymphocytes and B lymphocytes was 0.74 and 0.54 times lower in the DHC group than in the CON group, respectively. CAP, however, did not significantly change the number of T lymphocytes or B lymphocytes. No significant changes in the number of NK cells were observed among the three groups. CAP and DHC did not change the number of monocytes, eosinophils or basophils. No significant changes of the serum corticosterone levels were observed among the three groups. In conclusion, capsaicinoids decreased the number of acquired immunity cells, and increased the number of total WBCs and neutrophils without changing the number of monocytes, eosinophils or basophils. The magnitidue of these effects was relatively higher in DHC than in CAP.

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The present study was conducted to examine alterations in plasma free amino acid concentrations induced by squat exercise and branched-chain amino acid (BCAA) supplementation in young, untrained female subjects. In the morning on the exercise session day, participants ingested drinks containing either BCAA (isoleucine : leucine : valine=1 : 2.3 : 1.2) or dextrin (placebo) at 0.1 g/kg body weight 15 min before a squat exercise session, which consisted of 7 sets of 20 squats, with 3 min intervals between sets. In the placebo trial, plasma BCAA concentrations were decreased subsequent to exercise, whereas they were significantly increased in the BCAA trial until 2 h after exercise. Marked changes in other free amino acids in response to squat exercise and BCAA supplementation were observed. In particular, plasma concentrations of methionine and aromatic amino acids were temporarily decreased in the BCAA trial, being significantly lower than those in the placebo trial. These results suggest that BCAA intake before exercise affects methionine and aromatic amino acid metabolism.

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A method for the determination of γ-aminobutyric acid (GABA) in foodstuffs has been developed by combination of its dinitrophenylation and high-performance liquid chromatography (HPLC) using norleucine as an internal standard. GABA was converted to its stable derivative with 1-fluoro-2,4-dinitrobenzene and the derivative was extracted with ether. After evaporation of the extract, the residue was dissolved in 0.1 M NaOH and the solution was subjected to reversed-phase HPLC with an elution system of a linear gradient of methanol in 10 mM Tris-HCl buffer (pH 6.0) and a detection system monitoring the absorbance of the effluent at 400 nm. The present method was shown to be utilized as a satisfactory method for the determination of γ-aminobutyric acid in foodstuffs.

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Fresh cheese was prepared from caprine milk by isoelectric precipitation as a model experiment for reducing the allergenicity of milk. After acidic precipitation of casein, the β-lactoglobulin content in curd was determined by ELISA using monoclonal antibody (MAb-β209). The β-lactoglobulin content was very high in the fresh cheese obtained from heat-treated (85^oC) bovine or caprine milk, while that obtained from untreated milk contained none of this protein. Taking it into account that caprine milk has only a small amount of α_s1-casein, one of the major bovine milk allergens, the caprine fresh cheese sterilized after processing by precipitation may be useful as a protein source of low allergenicity.

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A previously developed current swimming pool for mice has been used to evaluate many food components that enhance endurance exercise performance. In this article, to improve reproducibility, reliability and sensitivity of this assay system, we improved the spout part to generate a uniform current and divided the pool into six lanes to avoid physical interference between swimming mice. The stability of the current flow was assessed by measuring the surface current speed and water volume from the spout part. Maximum swimming times of ddY and BALB/c mice were measured to assess the reproducibility of the maximum swimming time. The improvement in sensitivity compared to the original equipment was estimated under three physiological conditions: low carbohydrate diet feeding, low blood hemoglobin level, and carbohydrate supplementation during exercise. The new spout part improved uniformity and quick adjustment of surface current, yielding an increase of workload in a stepwise manner during swimming. Exercise workload was increased in proportion to surface current speed, as evidenced by cadence of kicks and serum lactic acid levels. The improved swimming pool showed higher reproducibility of swimming time until fatigue (p<0.0001). Correspondence between blood hemoglobin concentration and swimming time was improved in the swimming pool. The improved swimming pool yielded higher sensitivity for low carbohydrate diet feeding (p<0.0001) and carbohydrate supplementation during exercise (p<0.01) compared to the original swimming pool. The improvement of the swimming pool achieved higher sensitivity and reproducibility in assessing various diet and food components compared to the original swimming pool.

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