European Journal of Nutrition (v.55, #7)

The connection between iron and excessive adiposity has received much research interest. Although children and adolescents have unique developmental phases and nutritional demands, to date, reviews of iron in the overweight (OW) and obese (OB) have combined studies of children and adults or have focussed on adults. The aim of this review was to critically evaluate studies of the relationship between iron and OW and obesity in children and adolescents, with emphasis on iron status, oral iron response, dietary intake and systemic inflammatory markers.A PubMed search was conducted to identify relevant articles published up to December 2015. Combinations of the following keywords were used: iron, OW, OB, children, adolescents, diet, hepcidin, inflammation, fortification, supplementation, weight loss, trace elements, obesity, iron deficiency (ID), minerals.A higher prevalence of ID, or risk of ID, among OW and OB children and adolescents has been consistently observed. Chronic inflammation caused by excessive adiposity offers a plausible explanation for this finding, rather than dietary factors. However, future studies must employ screening for the presence of both acute and chronic infections and inflammatory conditions and report other factors such as pubertal status. Intervention studies, although few, indicate that OW and OB children and adolescents have reduced response to oral iron. Further trials are needed to explore the connection between body fat mass, inflammatory proteins and iron absorption, together with the effect of weight loss on iron status in iron-deficient OW and OB children and adolescents.
Keywords: Iron; Overweight; Children; Inflammation; High-income; Middle-income

Fatty acid composition in breastfeeding and school performance in children aged 12 years by Geertje W. Dalmeijer; Alet H. Wijga; Ulrike Gehring; Carry M. Renders; Gerard H. Koppelman; Henriette A. Smit; Lenie van Rossem (2199-2207).
Breastfeeding has been associated with improved cognition. It remains unclear whether long-chain polyunsaturated fatty acids (LC-PUFAs) play a role in this association. We assessed the association between LC-PUFA concentrations in infant feeding and school performance at age 12.Within a population-based birth cohort, we compared school performance of 277 non-breastfed children and 157 children who had fatty acid composition of their mothers’ breast milk measured. Two indicators of school performance were: (1) the score on a standardized achievement test and (2) the teacher’s advice regarding a child’s potential performance level in secondary education. Linear regression and multinomial logistic regression analyses were performed to assess the independent association between LC-PUFA content of breast milk and school performance.Girls, who received breast milk with a relative high content (above the median) of docosahexaenoic acid (DHA), had a higher Cito-test score (β = 2.96 points, 95 % CI 0.24; 5.69) than non-breastfed girls. Among the breastfed girls, each percentage point of higher content of total n-3 LC-PUFA (β = 4.55, 95 % CI 0.43; 8.66) and DHA (β = 7.09, 95 % CI 0.9; 13.3) was associated with a higher Cito-test score. The association between LC-PUFA content and teacher school advice showed a similar pattern. There was no association between LC-PUFA content and school performance in boys.Although a large part of the association between infant milk feeding and cognition seems to be explained by sociodemographic and lifestyle-related factors, a relative high content of n-3 PUFAs, especially DHA, in breast milk is associated with better school performance in 12-year-old girls but not in boys.
Keywords: Breastfeeding; Fatty acid composition; School performance; Birth cohort

Splanchnic tissues respond differently when piglets are offered a diet 30 % deficient in total sulfur amino acid for 10 days by José Alberto Conde-Aguilera; Nathalie Le Floc’h; Isabelle Le Huërou-Luron; Yves Mercier; Sophie Tesseraud; Louis Lefaucheur; Jaap van Milgen (2209-2219).
A deficient total sulfur amino acid (TSAA) supply has been reported to differently affect the amino acid composition of tissues, but limited information is available about its effects on the morphology and metabolic properties of splanchnic tissues.The amino acid composition, protein metabolism, glutathione concentration of the liver, proximal and distal jejunum, ileum and kidneys, and intestinal architecture were compared in 42-day-old piglets pair-fed either a diet deficient (TSAA−; 28 % deficiency) or sufficient (TSAA+) in TSAA for 10 days.The supply of TSAA had no effect on tissue weights, but influenced the amino acid composition in a tissue-dependent manner. Compared with animals receiving diet TSAA+, the concentrations of Met and Ser were higher in liver protein of TSAA− animals while the Cys concentration in protein was lower in the liver but higher in the distal jejunum. The TSAA supply had no effect on protein synthesis and proteolytic activities of tissues. Villus width and surface, and crypt surface were lower in the proximal jejunum of TSAA− versus TSAA+ pigs. Crypt surface in the ileum of TSAA− pigs was higher. Pigs receiving diet TSAA− had lower GSH and GSSG concentrations in the liver and proximal jejunum, but the GSH/GSSG ratio was decreased only in the liver.A greater nutritional priority appears to be given to splanchnic tissues so that its growth and protein metabolism can be maintained when the TSAA supply is limiting. The amino acid composition, glutathione status, and intestinal mucosa architecture are affected in a tissue-dependent manner.
Keywords: Tissue amino acid composition; Methionine + cysteine; Small intestine morphology; Protein synthesis; Glutathione; Proteolytic enzymes; Small intestine; Liver; Kidneys

Epidemiological evidence suggests that coffee consumption is associated with a lower risk of type 2 diabetes. Coffee contains caffeine and several other components that may modulate glucose regulation. The chlorogenic acids (CGA) in coffee have been indicated as constituents that may help to normalize the acute glucose response after a carbohydrate challenge. The aim of this study was to investigate whether two coffee beverages that differ in CGA content due to different roasting degrees will differentially affect glucose regulation.In a controlled crossover trial, 11 healthy fasted volunteers consumed 300 mL of either light (LIR) or dark (DAR) roasted coffee, or water, followed 30 min later by a 75-g oral glucose tolerance test (OGTT). Blood samples were drawn at baseline, 30, 60, and 120 min. Differences in glucose and insulin responses and insulin sensitivity index (ISI) were analyzed. The CGA and caffeine contents in the coffees were analyzed using UPLC-MS/MS.No differences in glucose area under the curve (AUC) were found between treatments. Glucose concentrations were higher at 60 min after ingestion of DAR compared with water, while ingestion of LIR showed similar glucose concentrations as ingestion of water. Insulin AUC was higher after ingestion of DAR compared with water, and both coffees raised insulin concentrations and reduced ISI compared with water, with no difference between the two coffees.Two coffees with different CGA contents did not differentially affect glucose or insulin responses during an OGTT, but both increased the insulin response compared with water.
Keywords: Coffee; Chlorogenic acids; Glucose tolerance; Insulin; Human intervention; Coffee roasting

Green tea extract activates AMPK and ameliorates white adipose tissue metabolic dysfunction induced by obesity by Andréa Rocha; Anaysa Paola Bolin; Claudia Andrea Lima Cardoso; Rosemari Otton (2231-2244).
Beneficial effects of green tea (GT) polyphenols against obesity have been reported. However, until this moment the molecular mechanisms of how green tea can modulate obesity and regulates fat metabolism, particularly in adipose tissue, remain poorly understood. The aim of this study was to evaluate the role of GT extract in the adipose tissue of obese animals and its effect on weight gain, metabolism and function (de novo lipogenesis and lipolysis), and the involvement of AMP-activated protein kinase (AMPK).Male Wistar rats were treated with GT by gavage (12 weeks/5 days/week; 500 mg/kg of body weight), and obesity was induced by cafeteria diet (8 weeks). Here, we show that obese rats treated with GT showed a significant reduction in indicators of obesity such as hyperlipidemia, fat synthesis, body weight, and fat depots as compared to those treated with standard control diet. AMPK was induced in adipose tissue in rats that were treated with GT and likely restored insulin sensitivity, increased mRNA expression of GLUT4, reducing the concentrations of plasma and liver lipid content, also stimulating fatty acid oxidation in the same tissue. Importantly, repression of de novo lipogenesis in the adipose tissue, reduced lipid droplets in the liver, and the development of insulin resistance in diet-induced obese rats were accompanied by AMPK activation.Our study identified that metabolic changes caused by GT intake induced AMPK activation and modulate the expression of genes involved in metabolism, particularly in adipose tissue, thus offering a therapeutic strategy to combat insulin resistance, dyslipidemia, and obesity in rats.
Keywords: Obesity; Flavonoids; Metabolism; Gene expression; Polyphenols

High-fat diet induces cardiomyocyte apoptosis via the inhibition of autophagy by Hsiu-Ching Hsu; Ching-Yi Chen; Bai-Chin Lee; Ming-Fong Chen (2245-2254).
Excessive fat intake induces obesity and causes cardiac injury. Intracellular degradation process involving destruction of long-lived proteins and organelles maintains homeostasis for cells under stress. The purpose of this study was to explore the relation of high-fat diet (HFD)-induced cardiac injury and intracellular degradation process with regard to autophagy and ER stress.HFD feeding for 24 weeks induced hyperglycemia, hyperlipidemia, and cardiac hypertrophy in adult male C57BL/6 mice. In the heart, PARP cleavage, an indicator of apoptosis, levels of LC3-II and p62, indicators of autophagy, and CHOP, indicator of ER stress, were increased. A palmitate-treated cardiomyoblast (H9C2) cell culture was examined to explore how HFD induced myocardial injury. Excessive palmitate (400 μM) treatment induced apoptosis and increased the number of autophagosomes and acid vacuoles of H9C2 cells. Besides, it elevated the expression of LC3-II, p62, and PARP cleavage. Induction of autophagy by rapamycin ameliorated palmitate-induced apoptosis, while inhibition of autophagy by 3-methyladenine or LC3 siRNA exacerbated palmitate-induced apoptosis. Palmitate treatment also induced CHOP expression which is associated with ER stress.HFD can cause cardiac injury by induction of apoptosis which is associated with autophagy dysregulation and ER stress. In addition, autophagy deficiency augments cardiac apoptosis, suggesting that autophagy serves as a pro-survival role in lipotoxic condition.
Keywords: High-fat diet; Cardiac hypertrophy; Autophagy; Apoptosis; Palmitate

The objective of this study was to determine the effect of feeding a maternal diet supplemented with docosahexaenoic acid (DHA) while also containing adequate amounts of arachidonic acid on immune system development and function in suckled offspring and lactating rats.Sprague–Dawley dams were randomized to one of the two nutritionally adequate experimental diets 24–48 h prior to parturition: control diet (N = 12, 0 % DHA) or high DHA diet (N = 8, 0.9 % DHA of total fatty acids). Diets were fed throughout the lactating/suckling period (21 days), and then, dams and pups were terminated, and immune cell phenotypes and cytokine production by mitogen- or ovalbumin-stimulated splenocytes were measured.Feeding dams a high DHA diet resulted in a higher proportion of 18:3n-3, 22:5n-3 and 22:6n-3 found in pup’s stomach content (breast milk; P < 0.01). Feeding the high DHA diet had no impact on growth parameters or the ex vivo cytokine production by mitogen-stimulated splenocytes in both dams and pups. There was a higher proportion of OX12+CD80+ cells and a lower production of TGF-β by splenocytes after ovalbumin stimulation in pups from dams fed the DHA diet (both P < 0.05) while maintaining a similar IL-2 production. LPS-stimulated splenocytes from dams fed the high DHA diet produced more TNF-α versus control diet (P < 0.05).Overall, our results suggest that DHA supplementation in the maternal diet does not change the immune response to mitogens but positively affects the activation of B cells as well as the response to a potential food antigen upon challenge in suckled offspring.
Keywords: Immune system; Lactation; Spleen; Offspring; Development

Developmental changes in polyunsaturated fetal plasma phospholipids and feto-maternal plasma phospholipid ratios and their association with bronchopulmonary dysplasia by Wolfgang Bernhard; Marco Raith; Vera Koch; Christoph Maas; Harald Abele; Christian F. Poets; Axel R. Franz (2265-2274).
Docosahexaenoic (C22:6) and arachidonic acid (C20:4) are long-chain polyunsaturated fatty acids (LC-PUFA), essential to fetal development, and preferentially transported by plasma phospholipids.To characterize fetal and maternal plasma phospholipid changes during gestation, and to investigate whether LC-PUFA phospholipid profiles are associated with bronchopulmonary dysplasia (BPD).Cord plasma and parturient serum from N = 108 pregnancies [24–42 week postmenstrual age (PMA)] were collected. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were analyzed with tandem mass spectrometry. PMA-associated changes were quantified, and break point analyses served to describe nonlinear changes during gestation.PC and PE were lower in cord than in parturient samples. In parturients, PC decreased until 33 week PMA, but then re-increased, whereas in cord plasma, concentrations linearly decreased. Fetal PC and PC sub-group values correlated with maternal values. C20:4-PC was twofold higher in cord than in maternal samples throughout gestation. C22:6-PC values, however, exceeded maternal values only beyond 33 week PMA. Consequently, early preterm C20:4-PC-to-C22:6-PC ratio largely exceeded term infant values. In infants born before 28 week PMA, a low C20:4-PC-to-C22:6-PC ratio was associated with BPD severity.Fetal plasma LC-PUFA–PC composition correlates with maternal values. Fetal C20:4-PC exceeds maternal values throughout gestation, whereas C22:6-PC exceeds maternal values only beyond 33 week PMA, resulting in a low fetal C20:4-PC/C22:6-PC ratio only toward end gestation. A low C20:4-PC/C22:6-PC ratio before 28 week PMA is associated with BPD severity. These data point to a concept of PMA-adjusted ARA and DHA supplementation and, potentially, cord plasma phospholipid analysis for BPD prediction.
Keywords: Arachidonic acid; Docosahexaenoic acid; LC-PUFA; Linoleic acid; Plasma phospholipids; Phosphatidylcholine; Phosphatidylethanolamine; Tandem mass spectrometry; Fetal development

Reduction of postprandial blood glucose in healthy subjects by buns and flatbreads incorporated with fenugreek seed powder by Sathyasurya Daniel Robert; Aziz Al-safi Ismail; Wan Ishak Wan Rosli (2275-2280).
This study aimed to determine whether fenugreek seed powder could reduce the glycemic response and glycemic index (GI) when added to buns and flatbreads.In a randomised, controlled crossover trial, ten healthy human subjects (five men, five women) were given 50 g glucose (reference food, twice); buns (0 and 10 % fenugreek seed powder); and flatbreads (0 and 10 % fenugreek seed powder) on six different occasions. Finger prick capillary blood samples were collected at 0, 15, 30, 45, 60, 90 and 120 min after the start of the meal. The palatability of the test meals was scored using Likert scales.The incremental areas under the glucose curve value of buns and flatbreads with 10 % fenugreek (138 ± 17 mmol × min/L; 121 ± 16 mmol × min/L) were significantly lower than those of 0 % fenugreek bun and flatbreads (227 ± 15 mmol × min/L; 174 ± 14 mmol × min/L, P = <0.01). Adding 10 % fenugreek seed powder reduced the GI of buns from 82 ± 5 to 51 ± 7 (P < 0.01) and to the GI of flatbread from 63 ± 4 to 43 ± 5 (P < 0.01).These results suggest that replacing 10 % of refined wheat flour with fenugreek seed powder significantly reduces the glycemic response and the GI of buns and flatbreads. Thus, fenugreek powder may be a useful functional ingredient to reduce postprandial glycemia.
Keywords: Carbohydrate; Fenugreek; Food; Glycemic response

Nut-enriched bread is an effective and acceptable vehicle to improve regular nut consumption by Asika Devi; Alexandra Chisholm; Andrew Gray; Siew Ling Tey; Destynee Williamson-Poutama; Sonya L. Cameron; Rachel C. Brown (2281-2293).
Consuming 30 g of nuts/day is recommended to reduce chronic disease. However, nut consumption appears far from ideal among several populations. A potential strategy to increase consumption is to add nuts to a staple, for example, bread. Whether the health benefits and acceptability of nuts persist in this form is currently unknown. Thus, we examined the effects of consuming three nut-enriched breads on postprandial glycaemia, satiety, gastrointestinal tolerance, dietary intakes, and acceptance.In this controlled, crossover study, 32 participants were randomly allocated to receive one of four breads for 8 days each. Three breads contained either 30 g of finely sliced hazelnuts, 30 g semi-defatted hazelnut flour, or 15 g of each (amounts per 120 g bread) and were compared with a control nut-free bread. Blood glucose response was measured over 120 min, along with ratings of gastrointestinal discomfort. Appetite ratings and diet diaries were completed during each treatment period. Area under the blood glucose curve was significantly lower for the nut breads compared to the control bread (all P < 0.001), with no significant differences between the nut breads (all P ≥ 0.130). There were no significant differences in satiety (all P ≥ 0.135) or gastrointestinal symptoms (all P ≥ 0.102) between the breads. Acceptance was highest for the finely sliced hazelnut bread. Furthermore, consuming hazelnut-enriched bread improved diet quality, increasing monounsaturated fat, vitamin E, and dietary fibre intakes.Bread appears to be an effective and acceptable vehicle for increasing nut consumption, resulting in improved postprandial glycaemia and diet profiles. Long-term studies are now required.
Keywords: Postprandial glycaemic response; Nuts; Satiety; Appetite; Gastrointestinal tolerance; Acceptance

A multifunctional diet (MFD) was previously shown to reduce blood lipids, CRP and blood pressure in a 4-week intervention under weight-maintenance conditions. Here, MFD effects were evaluated in an 8-week intervention with no restriction for weight changes.Healthy subjects consumed MFD (23 subjects) or a control diet (CD) devoid of the functional components (24 subjects) in a “free-living” randomized controlled experiment. MFD included several functional concepts: low-glycemic-impact meals, antioxidant-rich foods, oily fish, viscous dietary fibers, soybean and whole barley kernel products, almonds and plant stanols. Measured outcomes were fasting blood values of lipids, glucose, insulin, GGT, CRP, HbA1c, PAI-1, GLP-1, GLP-2, body weight, blood pressure and breath hydrogen.At baseline, participants were 51–72 years old, with BMI between 25 and 34 and fasting glycemia  ≤ 6.1 mmol/L. Consumption of both diets resulted in similar weight loss after 8 weeks (−4 %; P  <  0.001). Compared to baseline, consumption of MFD reduced total serum cholesterol (−26 %; P  <  0.0001), LDL cholesterol (−35 %; P  <  0.0001), triglycerides (−16 %; P  < 0.05), LDL/HDL (−27 %; P  <  0.0001) and ApoB/ApoA1 (−15 %; P  <  0.0001). There were important net differences between diets, which remained significant after adjustment for body weight. Reduced systolic blood pressure, circulating GGT, HbA1c and insulin concentrations were observed with both MFD and CD with no difference between diets. The Reynolds cardiovascular risk score was decreased by 36 % (P  <  0.0001) with MFD. MFD increased breath hydrogen levels (120 %; P  <  0.05).Consumption of MFD decreased blood lipids and improved several other aspects of the cardiometabolic risk profile. This effect was not dependent on weight loss.
Keywords: Cardiometabolic diseases; Cardiovascular risk; Dietary prevention; Functional foods; Metabolic syndrome; Randomized controlled trial

Low-carbohydrate, high-fat diets have sex-specific effects on bone health in rats by Ayse Zengin; Benedikt Kropp; Yan Chevalier; Riia Junnila; Elahu Sustarsic; Nadja Herbach; Flaminia Fanelli; Marco Mezzullo; Stefan Milz; Martin Bidlingmaier; Maximilian Bielohuby (2307-2320).
Studies in humans suggest that consumption of low-carbohydrate, high-fat diets (LC–HF) could be detrimental for growth and bone health. In young male rats, LC–HF diets negatively affect bone health by impairing the growth hormone/insulin-like growth factor axis (GH/IGF axis), while the effects in female rats remain unknown. Therefore, we investigated whether sex-specific effects of LC–HF diets on bone health exist. Twelve-week-old male and female Wistar rats were isoenergetically pair-fed either a control diet (CD), “Atkins-style” protein-matched diet (LC–HF-1), or ketogenic low-protein diet (LC–HF-2) for 4 weeks. In females, microcomputed tomography and histomorphometry analyses were performed on the distal femur. Sex hormones were analysed with liquid chromatography–tandem mass spectrometry, and endocrine parameters including GH and IGF-I were measured by immunoassay.Trabecular bone volume, serum IGF-I and the bone formation marker P1NP were lower in male rats fed both LC–HF diets versus CD. LC–HF diets did not impair bone health in female rats, with no change in trabecular or cortical bone volume nor in serum markers of bone turnover between CD versus both LC–HF diet groups. Pituitary GH secretion was lower in female rats fed LC–HF diet, with no difference in circulating IGF-I. Circulating sex hormone concentrations remained unchanged in male and female rats fed LC–HF diets.A 4-week consumption of LC–HF diets has sex-specific effects on bone health—with no effects in adult female rats yet negative effects in adult male rats. This response seems to be driven by a sex-specific effect of LC–HF diets on the GH/IGF system.
Keywords: Nutrition; Sex hormones; Bone mineral density; Growth hormone; Insulin-like growth factor-I; Ketogenic diet

Dietary patterns are found to be associated with metabolic risk factors. We explored gender difference on the association between dietary patterns and the risk of metabolic syndrome (MetS) in the general Korean population. A total of 13,410 Korean adults (aged ≥19 years, 5384 men and 8026 women) who participated in the fifth KNHANES were studied. Dietary intake was assessed by the 24-h recall method. MetS was defined by the joint interim statement of the International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute. Multivariable-adjusted logistic regression analysis was performed to identify the relationship between dietary pattern and MetS and its components by gender.Three dietary patterns were derived using factor analysis by sex: traditional, Westernized, and healthy. The traditional pattern was positively associated with hypertriglyceridemia (P for trend = 0.0098), low high-density lipoprotein cholesterol (P for trend = 0.0007), elevated blood pressure (P for trend = 0.0328), and MetS (P for trend = 0.0003) in women only after adjusting for age, body mass index, socioeconomic status, and lifestyle factors. In contrast, the healthy pattern (HP) was negatively associated with abdominal obesity (P for trend = 0.0051) in women. For men, the HP was negatively associated with hypertriglyceridemia (P for trend = 0.0025) after adjustment for potential confounders. The Westernized pattern was not associated with MetS or its components in either men or women.There may be gender differences on the relationship between dietary patterns and metabolic risk factors in Korean population.
Keywords: Gender difference; Dietary patterns; Metabolic syndrome; Korean

Waist circumference, trunk and visceral fat cutoff values for detecting hyperinsulinemia and insulin resistance in children: the Healthy Growth Study by George Moschonis; Kalliopi Karatzi; Maria Christina Polychronopoulou; Yannis Manios (2331-2334).