Obesity has emerged as one of the major health threats worldwide. Moreover, an excessive body fat accumulation, which defines this disease, could lead to several associated clinical manifestations such as cardiovascular events, type 2 diabetes, inflammation, and some types of cancer. The appearance of these co-morbidities has been often related to an unbalanced oxidative stress. Therefore, antioxidant-based treatments could be considered as interesting approaches to possibly counteract obesity fat accumulation complications. In this context, it has been observed that vitamin C intake (ascorbic acid) is negatively associated with the occurrence of several conditions such as hypertension, gallbladder disease, stroke, cancers, and atherosclerosis, and also with the onset of obesity in humans and animals. Among the possible beneficial effects of ascorbic acid on obesity-related mechanisms, it has been suggested that this vitamin may: (a) modulate adipocyte lipolysis; (b) regulate the glucocorticoid release from adrenal glands; (c) inhibit glucose metabolism and leptin secretion on isolated adipocytes; (d) lead to an improvement in hyperglycemia and decrease glycosylation in obese-diabetic models; and (e) reduce the inflammatory response. Possibly, all these features could be related with the outstanding antioxidant characteristics of this vitamin. Thus, the present article reviews the up-to-date evidence regarding in vitro and in vivo effects of vitamin C in obesity and its co-morbidities.
Vitamin E plays a critical role as an antioxidant in several pathological conditions, including diabetes, cancer, cardiovascular diseases, and neurodegenerative disorders. Diabetes is a metabolic disorder of glucose due to the lack of adequate insulin production (type 1) or peripheral insulin resistance (type 2). Oxidative stress plays a major role in the pathogenesis of diabetes and its complications. The purpose of the present study was to determine α-tocopherol status and the expression of α-tocopherol-related proteins, including binding proteins and metabolizing enzymes, under streptozotocin (STZ)-induced type 1 diabetes in rat models. In STZ rats, plasma α-tocopherol levels decreased compared to the control rats, whereas hepatic α-tocopherol levels in the STZ rats were significantly increased. CuZn-superoxide dismutase (SOD) gene expression in the liver of STZ rats was markedly decreased, whereas Mn-SOD gene expression remained unaltered. Accelerated lipid peroxidation in the liver of STZ rats was observed and the hepatic expression of α-tocopherol transfer protein (α-TTP) in STZ rats decreased compared to that in the controls. The hepatic expression of cytochrome P450 4F2 (CYP4F2) and CYP3A2 genes in STZ rats also decreased. The reduced expression of hepatic α-TTP and CYP4F2 genes probably leads to decreased plasma α-tocopherol levels and elevated α-tocopherol levels in the liver of STZ rats. The altered expression of hepatic α-tocopherol-related proteins might regulate α-tocopherol status in type 1 diabetes. Determining the mechanism of modulating α-tocopherol status may be helpful in promoting antioxidant therapy in diabetes.
No study has documented Japanese children’s food portion sizes. Since this information is essential to establish valid measurement tools and effective education methods for dietary intake, we measured them using one-day, semi-weighed diet records (DRs) for 489 Japanese children aged 3–6 y. Each food’s frequency of appearance on the DRs was counted. If a child consumed a certain food more than once per day, an average weight for that food was calculated and used in the portion size calculation as that child’s representative value. In total, 67 food items were consumed by twenty or more children. We calculated the mean, standard deviation, median, minimum, and maximum portion size values for these food items. In addition to these 67 items, Chinese noodles and water were included in the analysis. The most frequently consumed food was well-milled rice (mean portion size for rice=79 g), which was consumed by 350 children, followed by soy sauce (4 g), eggs (26 g), and carrots (9 g). Among the five most frequently consumed foods, portion sizes of rice and pork but not milk, eggs, or carrots significantly increased with age, height, and weight. In multivariate linear regression analysis, however, the significant relationships between rice portion size and age were not observed. Regarding pork, only the relationship with height was significant. A sex difference was detected in the rice and milk portion sizes. Most of portion sizes observed here were apparently smaller than those reported among United Kingdom children. This study provides important basic information for the implementation of quantitative nutritional research and educational efforts for Japanese preschool children.
In animal models, Fe overload is associated with organ oxidative stress and tissue injury. In this context, luminal Fe may affect the mucosal barrier and function or generate a pathological milieu in the intestine that triggers epithelial cell stress. Here, we hypothesized that increased liver Fe levels resulting from dietary Fe overload may be associated with architectural changes in the cecal mucosa. Weanling male Wistar rats (n=7-10/group) were fed diets (modified from AIN-93G) containing adequate or supplemental Fe (approximately 10 times the recommended levels) for 4 and 12 wk. At euthanasia, the blood Hb was determined, and Fe analyses were performed in stool and liver samples using atomic absorption spectrophotometry. Cecal tissue was collected for histological and morphometric analysis. No significant differences were observed in the blood Hb or Hb Fe pool between groups in either period. Iron overload led to a higher fecal Fe excretion, whereas the liver Fe was increased only after 12 wk when compared with controls. After 4 wk, the consumption of Fe-overloaded diets resulted in changes in the mucosal architecture of the cecum, which were intensified after 12 wk. At this time, these changes were significantly correlated with the hepatic Fe content. These findings suggest that changes in the cecal mucosa may have occurred as a result of oxidative stress caused by excessive amounts of Fe in the intestinal lumen. The consequences of these effects on the intestinal absorption and its implications for liver Fe homeostasis should be considered in future studies.
-Gingerol possesses a variety of beneficial pharmacological and therapeutic properties, including anti-carcinogenic, anti-inflammatory, and anti-emetic activities. Although -gingerol is known to regulate the contraction of the intestine, its effect on intestinal ion transport is unclear. The aim of this study was to examine the role of -gingerol in the regulation of electrogenic ion transport in the rat intestine by measuring the transmural potential difference (ΔPD). -Gingerol induced significant positive ΔPD when administered to the serosal but not mucosal side of the colon, ileum, and jejunum; the highest effect was detected in the colon at a concentration of 10 μM. -Gingerol-induced increase in ΔPD was suppressed by ouabain, an inhibitor of Na+/K+-ATPase, whereas no effect was observed in response to bumetanide, an inhibitor of the Na+-K+-2Cl− co-transporter. In addition, ΔPD induction by -gingerol was greatly diminished by capsazepine, an inhibitor of the capsaicin receptor TRPV1. These results suggest that -gingerol induced the electrogenic absorption of sodium in the rat colon via TRPV1.
This study investigated the effects of the consumption of 1% or 2% (v/v) ethanol in drinking water for 12 wk on rats fed a high-fat diet. Body weight gain, food intake, and fluid intake were unaffected by ethanol intake. Adipose tissue weight, and serum glucose and lipids were unaffected. Compared to the control (no ethanol), 1% ethanol intake significantly reduced serum levels of alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and ammonia (p<0.05), whereas 2% ethanol intake did so to a lesser extent. Serum urate was significantly lower in both the 1% and 2% ethanol groups than that in the control group (p<0.05). The results suggest a low dose of ethanol has beneficial effects on liver function and serum urate in rats fed a high-fat diet.
Lactate is oxidized as an energy fuel during exercise, and it also plays a key role in the regulation of glycogen synthesis in the muscles and liver after exercise. Previous studies have suggested that lactate is converted to glycogen and stimulates glycogen synthesis. However, it remains unclear whether chronic post-exercise lactate administration can increase glycogen storage in skeletal muscle. We examined whether 3 wk of chronic post-exercise lactate administration with training can increase muscle glycogen storage and whether such changes are associated with monocarboxylate transporter 1 (MCT1) protein expression in mice. Mice were assigned to receive saline with training (SA+T group; n=6) or lactate with training (LA+T group; n=6). All mice performed 40 min of treadmill running at 25 m/min, following which they received saline or lactate (2.5 mg/g body weight), 6 d/wk for 3 wk. After 3 wk, glycogen concentration at rest was higher in the white tibialis anterior (TA; p<0.05, +34%), but not in the red TA, in the LA+T group. Protein expression of MCT1, the primary lactate transporter, was increased with chronic post-exercise lactate administration in the white TA (p<0.05, +32%), but not in the red TA. MCT1 protein expression was significantly correlated with muscle glycogen concentration in the red and white TA in both groups (p<0.05, r=0.969). These results suggest that chronic lactate administration after exercise increases MCT1 protein expression, which can be involved in the regulation of the observed increase in muscle glycogen storage after exercise training.
Maternal vitamin D deficiency causes pregnancy complications and delayed skeletal development in offspring. This study aimed at identifying demographic and lifestyle factors associated with vitamin D status in pregnant Japanese women. A total of 284 healthy pregnant women in the second trimester were recruited at a university hospital in Tokyo, between June 2010 and July 2011. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were measured using chemiluminescent immunoassay. We assessed vitamin D intake using a self-administered diet history questionnaire and asked participants about lifestyle variables, including daily duration of sunlight exposure and supplement use. The mean (SD) serum 25(OH)D concentration was 9.8 (4.7) ng/mL. Almost 60% of the participants had severe vitamin D deficiency (measured as 25(OH)D<10 ng/mL). Multiple regression analysis showed that multigravidity, pre-pregnancy non-underweight status, higher energy-adjusted vitamin D intake, and use of vitamin D supplements were correlated with higher serum 25(OH)D concentrations (β=0.245, β=−0.119, β=0.226, and β=0.197, respectively). In the summer investigation, women with longer durations of sunlight exposure had significantly higher serum 25(OH)D concentrations (β=0.201) that were unrelated to the factors outlined previously. In the winter investigation, women with a high education level had higher serum 25(OH)D concentrations than others (β=0.330). Our results would be useful for identifying pregnant women at a high risk of low vitamin D status, such as primigravidae and those with pre-pregnancy underweight status, low education level, low vitamin D intake, and short durations of sunlight exposure.
This study investigated the PKA-dependent inhibitory effect of pycnogenol (Pyc) on lipolysis using ob/ob mice and primary mouse adipocytes. Supplementation of Pyc at 30 mg/kg significantly reduced body weight gain and visceral fat mass. The serum and hepatic triglyceride (TG) and total cholesterol (TC) levels were reduced by Pyc supplementation, and high density lipoprotein (HDL)-cholesterol level significantly increased. In addition, hormone sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) mRNA levels increased with Pyc supplementation in adipose tissue of ob/ob mice. The treatment of primary cultured adipocytes with Pyc at 100 μg/mL significantly increased glycerol release, cAMP level by reduction of phosphodiestersae-3B (PDE3B), and HSL levels, but decreased protein levels of perilipin A and fatty acid synthetase (FAS). The PKA inhibitor (H89) clearly blocked the cellular levels of perilipin A and HSL, suggesting that Pyc promotes lipolysis of adipocytes through activation of cAMP-dependent PKA, resulting in induction of HSL and reduction of perilipin A. Therefore, this study may elucidate the possible mechanism of Pyc, which is a candidate for weight loss through stimulation of lipolysis.
We investigated the effects of dietary soybean peptides, particularly low-molecular-weight peptides, on serum and hepatic concentrations of lipids in rats. Soybean protein isolate (SPI) was digested with protease to produce low-molecular-weight peptides (LD) or a mixture of high- and low-molecular-weight peptides (HLD). Rats were fed diets containing 20% casein, SPI, LD or HLD as a nitrogen source, with or without 0.5% cholesterol, for 2 wk. Next, rats were fed cholesterol-free diets containing 0%, 5%, 10%, or 20% LD at the expense of casein for 2 wk. Serum triglyceride levels were the lowest in the LD group, and liver triglyceride levels were significantly lower in rats fed SPI and LD/HLD diets than in those fed casein diets, both in the presence and absence of dietary cholesterol. In addition, dietary LD significantly lowered serum and liver triglyceride levels in a dose-dependent manner. These results suggest that low-molecular-weight soybean peptides have a potent hypotriglyceridemic effect and may be beneficial for improving lipid metabolism.
Vitamin E is localized in membranes and functions as an efficient inhibitor of lipid peroxidation in biological systems. In this study, we measured the second-order rate constants (ks) for the reaction of tocotrienol homologues (α-, β-, γ-, and δ-Toc-3Hs) with the aroxyl radical (ArO•) used as a model for lipid peroxyl radicals (LOO•) in the membranes of egg yolk phosphatidylcholine (EYPC) vesicles by stopped-flow spectrophotometry, and compared them to those of tocopherol homologues (α-, β-, γ-, and δ-TocHs). The relative rate constants of Toc-3H homologues to α-Toc-3H in membranes (α/β/γ/δ=100/83.7/63.2/20.2) were not much different to those of TocH homologues to α-TocH (α/β/γ/δ=100/88.4/83.8/17.3). Each ks value of Toc-3H homologues in membranes was 60-80% of that of the corresponding TocH homologues except for the almost identical ks values of δ-homologues, but there was no difference in EtOH solution between each ks value of the corresponding homologues of Toc-3H and TocH. These results indicate that the difference of the alkyl-side chain structure of vitamin E causes a change in the mobility of vitamin E molecules and/or the location of their antioxidant OH-groups in membranes, resulting in lowered radical-trapping rates of Toc-3Hs. By use of the ratio of the kinh value of α-TocH with LOO• (3.20×106 M−1s−1) to the ks value of α-TocH with ArO• (8.05×104 M−1s−1) in chlorobenzene (that is, 39.8), the kinh value for the reaction of α-TocH with LOO• in membrane was estimated to be 1.03×105 M−1s−1.
Serum and tissue iodine concentration was measured in rats fed a diet supplemented with powdered kombu (Saccharina sculpera) or potassium iodide to evaluate the absorption of iodine from kombu. Eighteen male 5-wk-old Wistar rats were divided into three groups and fed a basal AIN93G diet (iodine content, 0.2 mg/kg) or the basal diet supplemented with iodine (183 mg/kg) either in the form of kombu powder or potassium iodine (KI) for 4 wk. There were no differences in weight gain or serum biochemistry tests (alanine aminotransferase and aspartate aminotransferase activity, and total serum cholesterol and triglyceride concentration) after iodine supplementation. In addition, serum levels of the thyroid hormones thyroxine and triiodothyronine, as well as thyroid-stimulating hormone, were not affected. On the other hand, serum and tissue (thyroid, liver and kidney) iodine concentrations were markedly elevated after iodine supplementation. There was no difference in thyroid iodine concentration between KI and kombu supplementation. However, there was a significant difference observed in the iodine concentrations of serum, liver and kidney between the two iodine sources; rats fed KI had iodine concentrations in these tissues 1.8 to 1.9 times higher than those in rats fed kombu powder. These results suggest that the absorption of iodine from kombu is reduced compared to that from potassium iodide.
Obesity is increasingly becoming associated with increased risk of atherosclerosis. Serum levels of the bile acid deoxycholic acid (DCA) are elevated in mice with obesity induced by a high-fat (HF) diet. Therefore, we investigated the influence of DCA on the functions of vascular smooth muscle cells (VSMCs) because the initiation and progression of atherosclerosis are associated with VSMC proliferation and migration. DCA induced c-jun N-terminal kinase (JNK) activation whereas a JNK inhibitor prevented DCA-induced VSMC proliferation and migration. Based on these findings, we examined whether DCA promotes the expression of platelet-derived growth factor β-receptor (PDGFRβ) that has a c-Jun binding site in its promoter region. The mRNA and protein expression levels of PDGFRβ were upregulated in VSMCs after a 24- and 48-h incubation with DCA, respectively. The effects of PDGF such as proliferation and migration of VSMCs were promoted after a 48-h incubation with DCA despite the absence of DCA during PDGF stimulation. These findings suggest that elevated serum concentrations of DCA are involved in the pathogenesis of atherosclerosis in HF-induced obesity.