Chronic stress affects brain areas involved in learning and emotional responses through modulation of neurotropic factors or neurotransmitters. Therefore, we investigated the role of exercise and thiamine supplementation on spatial memory and on brain-derived neurotrophic factor (BDNF) and acetylcholine (Ach) content in the hippocampus of the stressed animals. Male Wistar rats were randomly assigned to 4 groups (8 rats/group): control group; stress group; swimming and stress group; and thiamine and stress group. All animals were assessed by a T maze for spatial memory or open field test for locomotion and anxiety. BDNF and Ach were estimated in the hippocampus. Chronic immobilization stress resulted in a significant decrease in BDNF and Ach levels in the hippocampus and impairment in spatial memory functions and decreased basal activity. However, either swimming training or thiamine intake for 30 d was proved to induce a significant increase both in BDNF and Ach in conjunction with improved performance in the T maze, marked anxiolytic effect and enhanced ambulation in the open field test, as compared to the stress group. Interestingly, swimming-exercised rats showed significantly higher levels of BDNF versus thiamine-receiving rats, while thiamine-receiving rats showed higher locomotor activity and less freezing behavior in the open field test compared to the swimming group. It was concluded that decreased BDNF and Ach after stress exposure could be a mechanism for the deleterious actions of stress on memory function; swimming exercise or vitamin B1 supplementation for 30 d was a protective tool to improve coping with chronic stress by modulating BDNF and Ach content along with enhancement of memory functions and motor activities.
Formylcobalamin (formyl-Cbl), a C1-unit carrying corrinoid, and propionylcobalamin (propionyl-Cbl) were synthesized for the first time, and their properties were compared with those of acetylcobalamin (acetyl-Cbl). Formyl-Cbl, acetyl-Cbl, and propionyl-Cbl were decomposed by a NH2OH treatment, forming formo-, aceto-, and propionohydroxamic acids, respectively, which offers a proof for the presence of “activated” acyl groups and for their structures of Co-acyl-Cbls. These results, together with chromatographic, electrophoretic, and spectroscopic properties, indicate that the acyl-Cbls synthesized are actually formyl-Cbl, acetyl-Cbl, and propionyl-Cbl. Spectroscopic and electrophoretic properties were consistent with the σ-donor strength or trans-effect increasing in the order: formyl<acetyl<propionyl. All acyl-Cbls underwent the Co-C bond cleavage upon photo-irradiation with a tungsten light bulb as well as upon treatment with alkali, forming aquacobalamin (aqCbl) and hydroxocobalamin (OH-Cbl), respectively, under air. Formyl-Cbl was thermally unstable and decomposed to aqCbl, and the thermal stability in neutral solution was much lower than in diluted HCl. In contrast, acetyl-Cbl and propionyl-Cbl were heat-stable under these conditions. Formyl-Cbl was essentially unsusceptible to unbufferized KCN solution, although acetyl-Cbl and propionyl-Cbl were rapidly converted to dicyanocobalamin under the same conditions. Such abnormal behaviors of formyl-Cbl suggest that it mainly exists in a hydrated form as formaldehyde.
In Japan, the incidence of type 2 diabetes mellitus (T2DM) is increasing for several reasons, including increased consumption of sugar-sweetened beverages (SSBs). However, whether SSBs cause T2DM by excess of energy production resulting in obesity remains unclear. Therefore, the present study was designed to evaluate the effects of SSB intake on the development of T2DM in subjects with impaired glucose tolerance (IGT). Ninety-three subjects (30 males and 63 females) with IGT aged 40-69 y and residing in the Mihama district (southern Mie Prefecture, Japan) were included in the study. The mean observational period was 3.6 y. All subjects underwent the 75-g oral glucose tolerance test (OGTT) and completed a lifestyle questionnaire survey related to SSB intake. OGTT results and SSB intake were evaluated before and after the observational period. In addition, the correlation between SSB intake and development of T2DM was investigated. Of the 93 subjects, 20 (21.5%) developed T2DM (T2DM group) and demonstrated a significantly high SSB intake compared with the group that did not develop the disease (non-T2DM group). The odds ratio for the incidence of T2DM based on SSB intake was 3.26 (95% confidence interval, 1.17-9.06). The body mass index (BMI; kg/m2) and the homeostasis model assessment for insulin resistance (HOMA-R) values was significantly higher in the T2DM group than in the non-T2DM group, while the insulinogenic indices were significantly lower in the former than in the latter group. The sum of insulin secretion levels during OGTT was not significantly different between groups. SSB intake correlated with the predisposition for developing T2DM, possibly by influencing body weight, insulin resistance, and the ability of the pancreatic beta cells to effectively compensate for the insulin resistance.
Although iron is an essential trace metal, its presence in excess causes oxidative stress in the human body. Recent studies have indicated that iron storage is a risk factor for type 2 diabetes mellitus. Dietary iron restriction or iron chelation ameliorates symptoms of type 2 diabetes in mouse models. However, whether iron content in the body changes with the development of diabetes is unknown. Here, we investigated the dynamics of iron accumulation and changes in iron absorption-related genes in mice that developed obesity and diabetes by consuming a high-fat diet (HFD-fed mice). HFD-fed mice (18-20 wk) were compared with control mice for hematologic features, serum ferritin levels, and iron contents in the gastrocnemius muscle, heart, epididymal fat, testis, liver, duodenum, and spleen. In addition, the spleen was examined histologically. Iron absorption-related gene expression in the liver and duodenum was also examined. Hemoglobin and serum ferritin levels were increased in HFD-fed mice. The HFD-fed mice showed iron accumulation in the spleen, but not in the heart or liver. Increased percentages of the splenic red pulp and macrophages were observed in HFD-fed mice and iron accumulation in the spleen was found mainly in the splenic red pulp. The HFD-fed mice also showed decreased iron content in the duodenum. The mRNA expression of divalent metal transporter-1 (DMT-1), an iron absorption-related gene, was elevated in the duodenum of HFD-fed mice. These results indicate that iron accumulation (specifically accumulation in the spleen) is enhanced by the development of type 2 diabetes induced by HFD.
It is known that insulin resistance in skeletal muscle induces subsequent metabolic diseases such as metabolic syndrome (MetS). However, which genes are altered in the skeletal muscle by development of insulin resistance in animal models has not been examined. In this study, we performed microarray and subsequent real-time RT-PCR analyses using total RNA extracted from the gastrocnemius muscle of the MetS model, spontaneously hypertensive corpulent congenic (SHR/NDmc-cp) rats, and control Wistar Kyoto (WKY) rats. SHR/NDmc-cp rats displayed overt insulin resistance relative to WKY rats. The expression of many genes related to fatty acid oxidation was higher in SHR/NDmc-cp rats than in WKY rats. Among 18 upregulated genes, putative peroxisome proliferator responsive elements were found in the upstream region of 15 genes. The protein expression of ACOX2, an upregulated gene, and peroxisome proliferator-activated receptor (PPAR) G1, but not of PPARG2, PPARA or PPARD, was higher in the gastrocnemius muscle of SHR/NDmc-cp rats than that in WKY rats. These results suggest that insulin resistance in the MetS model, SHR/NDmc-cp rats, is positively associated with the expression of fatty acid oxidation-related genes, which are presumably PPARs’ targets, in skeletal muscle.
Curcumin is a major constituent of the spice turmeric and has various biological activities, including anticancer, antioxidant, and anti-inflammatory properties, as well as alcohol detoxification. However, because of its poor absorption efficiency, it is difficult for orally administered curcumin to reach blood levels sufficient to exert its bioactivities. To overcome this problem, several curcumin preparations with a drug-delivery system (DDS) have been developed to increase the bioavailability of curcumin after oral administration, and tested as functional foods and potential medical agents in humans. We have also produced capsules containing Theracurmin, curcumin dispersed with colloidal submicron-particles. To evaluate the absorption efficiency of three types of DDS curcumin, we performed a double-blind, 3-way crossover study. We compared plasma curcumin levels after the administration of Theracurmin and 2 other capsule types of curcumin with DDS, BCM-95 (micronized curcumin with turmeric essential oils) and Meriva (curcumin-phospholipid). Nine healthy subjects (male/female=5/4, age: 24-32 y old) were administered these 3 preparations of DDS curcumin, at commonly used dosages. Six capsules of Theracurmin, 1 capsule of BCM-95, and 2 capsules of Meriva contain 182.4±1.0, 279.3±10.7, and 152.5±20.3 mg of curcumin, respectively. The maximal plasma curcumin concentration (0-24 h) of Theracurmin was 10.7 to 5.6 times higher than those of BCM-95 and Meriva, respectively. Moreover, the area under the blood concentration-time curve at 0-24 h was found to be 11.0- and 4.6-fold higher with Theracurmin than BCM-95 and Meriva, respectively. These data indicate that Theracurmin exhibits a much higher absorption efficiency than other curcumin DDS preparations.
Jasmin BENSER, Jara VALTUEÑA, Jonatan R. RUIZ, Juan MIELGO-AYUSO, Christina BREIDENASSEL, German VICENTE-RODRIGUEZ, Marika FERRARI, Kurt WIDHALM, Yannis MANIOS, Michael SJÖSTRÖM, Denes MOLNAR, Sonia GÓMEZ-MARTÍNEZ, Antony KAFATOS, Gonzalo PALACIOS, Luis A. MORENO, Manuel J. CASTILLO, Peter STEHLE, Marcela GONZÁLEZ-GROSS, on behalf of the HELENA Study Group
We examined the association of physical activity (PA), cardiovascular fitness (CVF) and fatness with total homocysteine (tHcy) concentrations in European adolescents. The present study comprised 713 European adolescents aged 14.8±1.2 y (females 55.3%) from the multicenter HELENA cross-sectional study. PA was assessed through accelerometry, CVF by the 20-m shuttle run test, and body fat by skinfold thicknesses with the Slaughter equation. Plasma folate, cobalamin, and tHcy concentrations were measured. To examine the association of tHcy with PA, CVF, and fatness after controlling for a set of confounders including age, maturity, folate, cobalamin, creatinine, smoking, supplement use, and methylenetetrahydrofolate reductase 677 genotype (CC 47%, CT 43%, TT 10%), bivariate correlations followed by multiple regression models were performed. In the bivariate correlation analysis, tHcy concentrations were slightly negatively correlated (p<0.05) with CVF in females (measured both by stages: r=−0.118 and by VO2max: r=−0.102) and positively with body mass index (r=0.100). However, daily time spent with moderate and vigorous PA showed a weak positive association with tHcy in females (p<0.05). tHcy concentrations showed a tendency to decrease with increasing CVF and increase with increasing BMI in female European adolescents. However, tHcy concentrations were positively associated with moderate and vigorous PA in female European adolescents.
“Shushoku,” “Shusai,” and “Hukusai” are staple food, main dish, and side dish, respectively. The recommended meal in Japan is a combination of “Shushoku,” “Shusai,” and “Hukusai”; however, it remains unclear whether there is an association between the frequency of these meals and intake of nutrients and food groups. This cross-sectional study examined the association between the frequency of meals combining “Shushoku, Shusai, and Hukusai” and intake of nutrients and food groups among 664 Japanese young adults aged 18-24 y. The dietary habits of the subjects during the preceding month were assessed using a validated brief-type self-administered diet history questionnaire. The frequency of meals combining “Shushoku, Shusai, and Hukusai” was self-reported according to four categories: “less than 1 d or 1 d/wk,” “2 or 3 d/wk,” “4 or 5 d/wk,” and “every day.” In both women and men, there was an association between the higher frequency of these meals and higher intake of the following food groups: pulses, green and yellow vegetables, other vegetables, mushrooms, seaweeds, fish and shellfish, and eggs. Moreover, there was an association with higher intake of protein, polyunsaturated fat, n-6 and n-3 polyunsaturated fat, total dietary fiber, soluble and insoluble dietary fiber, β-carotene, α-tocopherol, vitamin K, thiamin, riboflavin, folate, pantothenic acid, vitamin C, potassium, calcium, magnesium, iron, and copper, and lower intake of carbohydrate in both women and men. Our findings support the hypothesis that the meals combining “Shushoku, Shusai, and Hukusai” may be associated with intake of many food groups and nutrients among Japanese young adults.
The aim of this study was to investigate the interaction between psychological stress (PS) and drinking status in relation to diet among middle-aged Japanese men and women in a large-scale cross-sectional study. The study population included 5,587 middle-aged Japanese men and 2,718 middle-aged Japanese women who underwent annual health checkups. The subjects were divided into 2 groups (non-drinkers and drinkers) and classified as having low, moderate, or high self-reported PS levels. Energy-adjusted food and nutrient consumption was assessed with a validated food frequency questionnaire. Using a general linear model, food and nutrient consumption was estimated for each self-reported PS level in the 2 groups (non-drinkers and drinkers) and the interactions between self-reported PS levels and drinking status were calculated. In men, pork and beef; squid, octopus, shrimp, and clams; eggs; mushrooms; Japanese-style sweets; ice cream; bread; Chinese noodles; coffee; and soda as foods and protein, animal protein, fat, animal fat, carbohydrate, monounsaturated fatty acid, polyunsaturated fatty acid (PUFA), n-3 PUFA, n-6 PUFA, cholesterol, vitamin D, vitamin B2, vitamin B6, vitamin B12, niacin, pantothenic acid, magnesium, phosphorus, and zinc as nutrients significantly interacted with self-reported PS levels and drinking status (p for interaction <0.05 for all). No specific interactions were found in women. These findings suggest interactions between PS levels and drinking status with consumption of some foods and nutrients, especially macronutrient intake, in men but not in women.
Recent evidence suggests that immune cells play an important role in differentiation of inflammatory macrophages in adipose tissue, which contributes to systemic chronic inflammation. Dietary ribonucleic acid (RNA) has been shown to modulate immune function. We hypothesized that RNA affects immune cell function in adipose tissue and then improves inflammatory response in adipose tissue. C57/BL6 mice and recombination activating gene-1 (RAG-1) knockout mice on a C57BL/6 mice background were fed a high-fat diet containing 1% RNA for 12 wk. An oral glucose tolerance test was performed. Supplementation of dietary RNA in C57BL/6 mice fed a high-fat diet resulted in a smaller area under the curve (AUC) after oral glucose administration than that for control mice. The mRNA expression levels of inflammation-related cytokines in adipose tissue and serum interleukin-6 levels were reduced by dietary RNA supplementation. Interestingly, reduction of the AUC value by RNA supplementation was abolished in T and B cell-deficient RAG-1 knockout mice. These results indicate that RNA improves inflammation in adipose tissue and reduces the AUC value following oral glucose administration in a T and B cell-dependent manner.
Kaempferia parviflora extract (KP) has been reported to have a preventive effect on obesity in mice, probably by increasing energy expenditure (EE). The aims of the current study were to examine the acute effects of KP ingestion on whole-body EE in humans and to analyze its relation to the activity of brown adipose tissue (BAT), a site of non-shivering thermogenesis. After an oral ingestion of an ethanol extract of KP, EE increased significantly, showing a maximal increase of 229±69 kJ/d at 60 min, while it did not change after placebo ingestion. To evaluate BAT activity, the subjects underwent fluorodeoxyglucose-positron emission tomography, and divided into two groups with high- and low-BAT activities. A similar and greater response of EE to KP ingestion was observed in the high-BAT group (351±50 kJ/d at 60 min), but not in the low activity group. Placebo ingestion did not cause any significant EE change in either group. These results indicate that a single oral ingestion of the KP extract can potentially increase whole-body EE probably through the activation of BAT in healthy men, and may be useful as an anti-obesity regimen.
Antithrombotic effects of water-extractive components (extracts) from heshiko and narezushi, traditional fermented aquatic products in Japan, were investigated in terms of blood coagulation and fibrinolysis by means of animal experiments. Blood clot formation was suppressed by administration of heshiko and narezushi extracts to both groups of Wistar rats fed artificial and high-fat experimental diets. Prothrombin time and activated partial thromboplastin time of plasma prepared from the rats, as indices of blood coagulation, were not prolonged by administration of heshiko or narezushi extracts. In contrast, the activities of plasmin and tissue plasminogen activator (tPA), key enzymes in the fibrinolytic system, were significantly increased by administration of heshiko and narezushi extracts. These results suggest that the anticoagulating effects of heshiko and narezushi extracts are associated with the promotion of the fibrinolytic system via enhancement of plasmin and tPA activities.
Persimmon is widely eaten in Asia and the nutritional components of young and mature persimmons differ. Although raw young persimmon has a strong bitter taste and is difficult to eat, the beneficial health effects of young persimmon powder have attracted attention in recent years. Young persimmon has been suggested to have hypolipidemic activity as well as other biological effects. However, there has been little investigation of the beneficial effects of young persimmon. In the present study, we investigated the antioxidative effects of persimmon in an animal study and compared the effects of young persimmon and mature persimmon. Six-week-old male F344 rats were divided into three groups and fed a standard diet, young persimmon diet, or mature persimmon diet for 4 wk. The young persimmon and mature persimmon groups were fed a diet containing 5% (w/w) freeze-dried young or mature persimmon. We analyzed phosphatidylcholine hydroperoxide (PCOOH) levels in the rats as a biomarker of membrane lipid peroxidation. Our study showed that plasma PCOOH levels were significantly lower in the young persimmon group (36.1±28.5 pmol/mL plasma) than in the control group (120±66 pmol/mL plasma). No significant difference was observed between the mature persimmon group (57.3±15.6 pmol/mL plasma) and the control group. It is possible that ascorbic acid and soluble tannin contribute to the difference in the antioxidant effects of young and mature persimmons. These results indicated that intake of young persimmon contributes to the reduction of plasma phospholipid hydroperoxide levels in rats.
Hypsyzigus marmoreus (HM), an edible mushroom, has several effects, including antitumor, antioxidant and anti-allergy properties. On the other hand, the possibly useful effect of HM in diabetic mice has not as yet been elucidated. In this study, we showed treatment with a water soluble extract from HM (EHM) to reduce fat deposits without affecting body weight loss in KK-Ay mice. EHM treatment also abolished the expressions of pro-inflammatory adipokines, such as tumor necrosis factor α and monocyte chemoattractant protein 1, as compared with vehicle treatment. The expressions of uncoupling protein 3 and peroxisome proliferator-activated receptor gamma coactivator 1α in the soleus muscles of EHM treatment groups were significantly elevated as compared to those in vehicle-treated muscle tissues. These results raise the possibility that EHM can regulate both obesity and insulin resistance.
Lysozyme (EC 22.214.171.124) is a hydrolytic enzyme that cleaves the β-(1,4)-glycosidic bond between N-acetylmuramic acid and N-acetylglucosamine in peptidoglycan, a major bacterial cell wall polymer. In the food industry, lysozyme is used as an additive mainly in the production of wine and beer. Lysozyme was found to be localized in the egg shell membrane. In this study, we found that lysozyme was easily purified from the egg shell membrane and that the enzyme also had antibacterial activity. Furthermore, we found that the antibacterial activity of purified lysozyme from the egg shell membrane was lower than that of purified lysozyme from the egg white at alkaline pH. The method for rapid purification of lysozyme developed in this study should contribute to the food industry.