European Journal of Nutrition (v.50, #8)

Oxidized fats are known to induce oxidative stress resulting in the up-regulation of antioxidant enzymes, with the underlying mechanism being unclear. It is known, however, that the response of tissues to oxidative stress is mediated by redox-sensitive transcription factors such as NF-κB and Nrf2. The aim of this study, therefore, was to test the hypothesis that ingestion of an oxidized fat causes activation of these transcription factors in the small intestinal mucosa.Female mice were randomly assigned to 2 groups of 12 mice each and administered orally by gavage either oxidized or fresh fat once per day.After 6 days of treatment, mice were killed, intestinal mucosa was isolated, and nuclear concentration of NF-κB and Nrf2 and expression of NF-κB- and Nrf2-regulated oxidative stress-responsive genes were determined. Oxidized fat markedly increased nuclear concentration of NF-κB and Nrf2 and transcript levels of oxidative stress-responsive genes, like aldo–keto reductase 1B8, vanin-1, glutathione peroxidase 1, and superoxide dismutase-1. In addition, oxidized fat increased the concentrations of PPAR-regulated genes.The activation of oxidative stress-sensitive pathways likely reflects an adaptive response of the intestinal mucosa to prevent oxidative damage to the intestinal mucosa.
Keywords: Oxidized fat; Mucosa; Nrf2; NF-κB; Mouse

Effects of pre- and early postnatal exposure to maternal high-protein diets are not well understood. Transcription profiling was performed in male mouse offspring exposed to maternal high-protein diet during pregnancy and/or lactation to identify affected hepatic molecular pathways.Dams were fed isoenergetic diets with control (20% w/w) or high protein levels (40%). The hepatic expression profiles were evaluated by differential microarray analysis 3 days (d3) and 3 weeks (d21) after birth. Offspring from three different high-protein dietary groups, HP (d3, high-protein diet during pregnancy), HPHP (d21, high-protein diet during pregnancy and lactation) and CHP (d21, control diet during pregnancy and high-protein diet during lactation), were compared with age-matched offspring from dams fed control diet.Offspring body and liver mass of all high-protein groups were decreased. Prenatal high-protein diet affected hepatic expression of genes mapping to the acute response/complement system and the GH/JAK/STAT/IGF signalling pathways. Maternal exposure to high-protein diet during lactation affected hepatic gene expression of the same pathways but additionally affected genes mapping to protein, fatty acid, hexose and pyruvate metabolism.(1) Genes of the acute response/complement system and GH/JAK/STAT/IGF pathways were down-regulated in offspring of dams exposed to high-protein diets during pregnancy and/or lactation. (2) Genes related to nutrient and energy metabolism, however, were only affected when high-protein diet was administered during lactation. (3) Modulation of the GH/JAK/STAT/IGF pathway might be responsible for reduced body and liver masses by maternal high-protein diet.
Keywords: Diet; Early nutrition; Gene expression profiling; High-protein; Lactation; Microarray analysis; Mouse; Neonate; Pregnancy

Erythrocyte membrane phospholipid polyunsaturated fatty acids are related to plasma C-reactive protein and adiponectin in middle-aged German women and men by Cornelia Enzenbach; Janine Kröger; Vera Zietemann; Eugène H. J. M. Jansen; Andreas Fritsche; Frank Döring; Heiner Boeing; Matthias B. Schulze (625-636).
Modulation of circulating inflammatory markers and adiponectin may link PUFA to risk of diabetes and cardiovascular diseases. We investigated erythrocyte n-6 and n-3 PUFA in relation to plasma C-reactive protein (CRP) and adiponectin, and whether the Pro12Ala polymorphism in the PPARγ2 gene (PPARG2) modified these associations.We conducted a cross-sectional analysis among 1,222 women and 758 men participating in the EPIC-Potsdam study.Most notably, in both sexes, higher linoleic acid (LA) was related to lower CRP (geometric mean outcome [mg/L], quintile 1, quintile 5, p for trend ≤ 0.01 unless otherwise stated: 0.95, 0.61 [women], 0.67, 0.51 [men]) and higher adiponectin (7.9, 9.1 [women], 5.3, 6.1 [men]), whereas higher γ-linolenic acid (GLA) and dihomo-γ-linolenic acid (DGLA) were related to higher CRP (GLA: 0.63, 0.92 [women], 0.55, 0.70, p = 0.08 [men], DGLA: 0.55, 1.07 [women], 0.52, 0.76 [men]) and lower adiponectin (GLA: 8.6, 8.0 [women], 5.8, 5.4, p = 0.08 [men], DGLA: 9.2, 7.9 [women], 5.9, 5.4, p = 0.08 [men]) adjusting for age and lifestyle. The associations mostly did neither strongly nor significantly vary by PPARG2 genotype. In women, Pro12Ala appeared to interact with arachidonic acid on CRP (p = 0.04), as well as with docosatetraenoic acid on CRP (p = 0.08) and adiponectin (p = 0.02).Our findings suggest that erythrocyte PUFA, particularly LA and n-6 higher unsaturated fatty acids, are related to circulating CRP and adiponectin. They do not indicate that PUFA strongly interact with the PPARG2 Pro12Ala variant on these risk markers.
Keywords: Adiponectin; C-reactive protein; Dihomo-gamma-linolenic acid; Fatty acids; Molecular epidemiology

Effect of dietary protein on heme iron uptake by Caco-2 cells by Pía Villarroel; Sebastián Flores; Fernando Pizarro; Daniel López de Romaña; Miguel Arredondo (637-643).
To study heme iron bioavailability and the role of dietary protein (animal and vegetable) on iron uptake using an in vitro model (Caco-2 cell line).Caco-2 cells were seeded in bicameral chambers with different animal (beef, chicken or fish) or vegetable (peas, lentils, and soybeans) proteins or with pure animal (collagen and casein) or vegetable (gliadin, zein, and glutein) protein extracts. The effect of each protein over heme iron absorption was assessed.Intact heme uptake was higher than either heme plus albumin or digested heme plus albumin, but lower than digested heme. White meal exerted the highest inhibitory effect on hemin uptake. Heme iron uptake decreased in the presence of all legume extracts, but was not significantly different among them (one-way ANOVA, NS). Pure animal (collagen and casein) and vegetable (zein and glutelin) proteins increased heme iron uptake, except for gliadin.Animal and vegetable protein in general decreased heme iron uptake. However, purified animal and vegetable protein induce an increase in heme iron uptake.
Keywords: Heme absorption; Bioavailability; Uptake; Transport; Caco-2 cells

A role for suppressed bone formation favoring catch-up fat in the pathophysiology of catch-up growth after food restriction by Xiangfei Guo; Weihong Yang; Jiaxiang Ni; Mingwei He; Liqiang Yang (645-655).
Catch-up growth is always companied with later development of obesity and osteoporosis that are two interrelated clinical entities. However, the potential mechanism of the link between them during catch-up growth is unknown.Rats were divided into two groups. Rats of the normal control (NC) group were offered ad libitum access to food, while rats of CUGFR group were food restricted for 4 weeks, and then were allowed full access to food for 0, 2, 4 weeks, respectively. The fat percentage and distribution, bone mineral density, biochemical and histological indexes of bone were detected. Moreover, the expression of adipogenic or osteoblastic differentiation-related genes of mesenchymal stem cells (MSCs) was also determined.Catch-up growth led to a rapid visceral fat accumulation. Although there was no difference in the histological indexes of bone between NC group and CUGFR group, the bone turnover marker, serum Bone Gla-protein (s-BGP), decreased in CUGFR group. The adipogenic differentiation-related gene of MSCs, PPAR-gamma, was significantly higher than that of NC group especially when catch-up growth for 4 weeks. Nevertheless, the osteoblastic differentiation-related gene of MSCs, Runx2, was increased but failed to reach the levels of the controls eventually. Both protein and mRNA of TAZ, a main transcriptional modulator of MSCs differentiation, failed to catch up even after being allowed full access to food for 4 weeks.CUGFR induces the differential differentiation of MSCs, potentially suppressing bone formation and favoring catch-up fat, which might be responsible for the increased risk of osteoporosis and obesity during CUGFR.
Keywords: Catch-up growth; Obesity; Osteoporosis; Mesenchymal stem cells

Hypovolemic state: age-related influence of water restriction on cardiac nitric oxide synthase in rats by Andrea Lorena Fellet; Patricia Raquel Arza; Myriam Nuñez; Cristina Teresa Arranz; Ana María Balaszczuk (657-664).
We have assessed the influence of water restriction stress on the nitric oxide (NO) synthase in heart and aorta tissues in young 2-month-old and middle-aged 12-month-old rats.Animals were divided into control and 24- and 72-h water-deprived groups. We evaluated systolic blood pressure (SBP), biochemical parameters, nitrate and nitrite urinary excretion (UNOx), NADPH-diaphorase activity, and protein levels of NOS in the right atria, left ventricle, and thoracic aorta tissues.Water restriction during 72 h increased SBP (16%) in 2-month-old rats but decreased it after 24 and 72 h (9 and 15%, respectively) in 12-month-old rats. Atria, aorta endothelium, and smooth muscle NOS activity increased (32, 63, and 88%, respectively) only after 72 h of water restriction in 2-month-old rats. It also increased not only after 72 h but also after 24 h in atria (27 and 18%, respectively) and in ventricle (39 and 67%, respectively) in 12-month-old rats. Meanwhile, in this group’s aorta smooth muscle, the enzyme activity decreased (16 and 7%, respectively). A major difference seen between ages was the changes in UNOx excretion, which decreased in the younger in 24 and 72 h (47 and 81%, respectively) and increased in the middle-aged rats (193 and 389%, respectively). Water restriction did not change cardiovascular endothelial and neuronal NOS protein levels in any group.NO pathways could contribute to the development of age-related cardiovascular adaptation to volume depletion induced by water restriction.
Keywords: Heart; Aorta; Nitric oxide synthases; Water restriction; Age

Glucocorticoid treatment, immobility, and constipation are associated with nutritional risk by Jean-Pierre Gutzwiller; Josef Aschwanden; Samuel Iff; Michèle Leuenberger; Martin Perrig; Zeno Stanga (665-671).
The hypothesis of this clinical study was to determine whether glucocorticoid use and immobility were associated with in-hospital nutritional risk.One hundred and one patients consecutively admitted to the medical wards were enrolled. Current medical conditions, symptoms, medical history, eating and drinking habits, diagnosis, laboratory findings, medications, and anthropometrics were recorded. The Nutrition Risk Score 2002 (NRS-2002) was used as a screening instrument to identify nutritional risk.The results confirmed that glucocorticoid use and immobility are independently associated with nutritional risk determined by the NRS-2002. Constipation could be determined as an additional cofactor independently associated with nutritional risk.Glucocorticoid treatment, immobility, and constipation are associated with nutritional risk in a mixed hospitalized population. The presence of long-time glucocorticoid use, immobility, or constipation should alert the clinician to check for nutritional status, which is an important factor in mortality and morbidity.
Keywords: Malnutrition; Nutritional risk screening; Glucocorticoid treatment; Immobility; Constipation

Lack of effect of oral administration of resveratrol in LPS-induced systemic inflammation by M. Larrosa; M. Azorín-Ortuño; M. J. Yañez-Gascón; M. T. García-Conesa; F. Tomás-Barberán; J. C. Espín (673-680).
The high mortality index due to sepsis and the lack of an effective treatment requires the search for new compounds that can serve as therapy for this disease. Resveratrol, a well-known anti-inflammatory natural compound, might be a good candidate for the treatment of sepsis. The aim of this work was to study the effects of oral administration of resveratrol, before and after sepsis initiation, on inflammation markers in a murine model of endotoxin-induced sepsis.Sprague–Dawley male rats were treated with resveratrol the 3 days prior to LPS administration and 45 min later. Hematological parameters, TNF-α, IL-1β and CINC-1, FRAP and TBARS levels were determined. Resveratrol and resveratrol-derived metabolites profile in plasma was compared after oral and intraperitoneal administration.Oral treatment with resveratrol had no apparent systemic protective effects. However, resveratrol reduced the levels of lipid peroxidation in the small intestine and colon. Importantly, the administration of LPS caused a decrease in resveratrol absorption. When resveratrol bioavailability after i.p. administration was compared to that observed after oral administration, a different profile of resveratrol metabolites was found in plasma.These results highlight the importance of studying the bioavailability of the assayed compounds in the experimental models used to be able to choose the best route of administration depending on the target organ and to determine which compounds or derived metabolites are effective treating the studied disease.
Keywords: Polyphenol; Lipopolysaccharide endotoxin; Sepsis; Cytokines; Bioavailability

Evaluation of the antioxidant properties of fruit and flavoured black teas by Anna Pękal; Paulina Dróżdż; Magdalena Biesaga; Krystyna Pyrzynska (681-688).
Antioxidant properties of the water extracts of the commercial bagged fruit and flavoured black teas were evaluated and compared with typical black teas of C. sinensis. Folin–Ciocalteu (FC) assay, cupric ion reducing antioxidant capacity (CUPRAC) and DPPH radical method were used for these purposes. The content of selected flavonoids and phenolic acids was also determined by high-performance liquid chromatography with tandem mass spectrometry in the negative electrospray ionization mode.Flavoured black teas contain significantly higher level of catechins, quercetin, and rutin, while the content of chlorogenic and caffeic acids as well as naringin and hesperidin was higher in fruit teas. Supplementation with these flavonoids could reduce blood glucose. In FC and DPPH assays, the antioxidant properties of studied tea infusion increases in the order: fruit tea < flavoured black tea > premium black tea, while in CUPRAC method, some aromatized teas exhibit the highest antioxidant properties. Tea infusions with nice smell of fruits would also support the human diet with some source of antioxidants.
Keywords: Fruit and flavoured teas; Antioxidant properties; Polyphenol content; CUPRAC; DPPH

Evidence for the role of α1A-adrenoceptor subtype in the control of renal haemodynamics in fructose-fed Sprague–Dawley rat by Mohammed H. Abdulla; Munavvar A. Sattar; Edward J. Johns; Nor A. Abdullah; Md. Abdul Hye Khan (689-697).
To explore the hypothesis that high fructose intake results in a higher functional contribution of α1A-adrenoceptors and blunts the adrenergically and angiotensin II (Ang II)-induced renal vasoconstriction.Twelve Sprague–Dawley rats received either 20% fructose solution [FFR] or tap water [C] to drink ad libitum for 8 weeks. The renal vasoconstrictor response to noradrenaline (NA), phenylephrine (PE), methoxamine (ME) and Ang II was determined in the presence and absence of 5-methylurapidil (5-MU) (α1A-adrenoceptor antagonist) in a three-phase experiment (pre-drug, low- and high-dose 5-MU). Data, mean ± SEM were analysed by ANOVA or Student’s unpaired t-test with significance at P < 0.05.FFR exhibited insulin resistance (HOMA index), hypertension and significant increases in plasma levels of glucose and insulin. All agonists caused dose-related reductions in cortical blood perfusion that were larger in C than in FFR while the magnitudes of the responses were progressively reduced with increasing doses of 5-MU in both C and FFR. The degree of 5-MU attenuation of the renal cortical vasoconstriction due to NA, ME and Ang II was significantly greater in the FFR compared to C.Fructose intake for 8 weeks results in smaller vascular response to adrenergic agonists and Ang II. The α1A-adrenoceptor subtype is the functional subtype that mediates renal cortical vasoconstriction in control rats, and this contribution becomes higher due to fructose feeding.
Keywords: Renal vasoconstriction; Noradrenaline; 5-methylurapidil, fructose, α1A-adrenoceptors

Duodenal cytochrome b (Cybrd 1) and HIF-2α expression during acute hypoxic exposure in mice by Gladys O. Latunde-Dada; Lan Xiang; Robert J. Simpson; Andrew T. McKie (699-704).
Recent evidence suggests that the duodenum can regulate iron absorption independently of hepcidin via the transcription factor Hif-2α acting directly on the transcription of the proteins involved in the iron transport. The current study investigates the temporal relationship between Dcytb and Hif-2α during early hypoxic stimulus in the enterocyte in vivo.Duodenal Dcytb and Hif-2α protein expression was analysed by Western blot technique while gene regulation was determined by quantitative PCR.Both Dcytb and Hif-2α protein expression were increased during the first hours of hypoxic duration. A change in hepcidin expression however, was significant only at 72 h hypoxia. Increased iron absorption reported in early hypoxia could be accounted for in part by the enhancement of Dcytb expression by Hif-2α in the duodenum.Modulation of Hif-2α predominates over hepcidin in the regulation of intestinal iron absorption during short hypoxic duration. The intestine exerts regulatory mechanisms in the dietary absorption of iron into systemic circulation.
Keywords: Iron; Hypoxia; Dcytb; Hif-2α

Anthocyanins in the diet of infants and toddlers: intake, sources and trends by Claudia Drossard; Ute Alexy; Katja Bolzenius; Clemens Kunz; Mathilde Kersting (705-711).
Anthocyanins, a colourful group of flavonoids in many fruits and vegetables, are proposed to provide positive impact on human health. However, intake estimations have almost exclusively been conducted in adult populations. As infants and toddlers are a promising age group for health promotion, we examined their anthocyanin intake (as anthocyanidins), food sources and trends of age and time in anthocyanidin density.Anthocyanidin content values from the USDA Database were assigned to foods consumed in 4,617 3-day weighed dietary records from 1990 to 2009 by 942 3–36-month-old subjects of the DONALD Study. As we assume that anthocyanidins found in bananas do not originate from anthocyanins, the anthocyanidin value for bananas was excluded from our analysis. To investigate age and time trends in anthocyanidin density, polynomial mixed regression models were used.Median anthocyanidin intake was zero in young infants and around 4 mg/day in older infants and toddlers, strawberries and pomaceous fruit representing the main sources. Anthocyanidin density increased from 6 to 18 months of age, followed by a slight decrease till 36 months of age. During the 20-year study period, a decrease in density in infants was observed, but a slight increase in toddlers.Anthocyanidin density in the diet seems to increase notably from infancy to toddlerhood and to have decreased in the youngest over the last 20 years. These first observations in a German population of infants and toddlers need to be extended by further studies examining anthocyanin intake in these age groups in other countries.
Keywords: Anthocyanin intake; Infants; Toddlers; Age and time trends; Banana