Dietary High Salt Intake Exacerbates SGK1-Mediated T Cell Pathogenicity in L-NAME/High Salt-Induced Hypertension.

Sodium chloride (NaCl) activates Th17 and dendritic cells in hypertension by stimulating serum/glucocorticoid kinase 1 (SGK1), a sodium sensor. Memory T cells also play a role in hypertension by infiltrating target organs and releasing proinflammatory cytokines. We tested the hypothesis that the role of T cell SGK1 extends to memory T cells. We employed mice with a T cell deletion of SGK1, SGK1fl/fl × tgCD4cre mice, and used SGK1fl/fl mice as controls. We treated the mice with L-NAME (0.5 mg/mL) for 2 weeks and allowed a 2-week washout interval, followed by a 3-week high-salt (HS) diet (4% NaCl). L-NAME/HS significantly increased blood pressure and memory T cell accumulation in the kidneys and bone marrow of SGK1fl/fl mice compared to knockout mice on L-NAME/HS or groups on a normal diet (ND). SGK1fl/fl mice exhibited increased albuminuria, renal fibrosis, and interferon-γ levels after L-NAME/HS treatment. Myography demonstrated endothelial dysfunction in the mesenteric arterioles of SGK1fl/fl mice. Bone marrow memory T cells were adoptively transferred from either mouse strain after L-NAME/HS administration to recipient CD45.1 mice fed the HS diet for 3 weeks. Only the mice that received cells from SGK1fl/fl donors exhibited increased blood pressure and renal memory T cell infiltration. Our data suggest a new therapeutic target for decreasing hypertension-specific memory T cells and protecting against hypertension.

Low-quality protein modulates inflammatory markers and the response to lipopolysaccharide insult: the case of lysine.

The relationship between non-communicable diseases and eating behaviour has long been attributed to a surplus of food and energy. However, the increase in the prevalence of non-communicable disease and their underlying low-grade inflammatory milieu among people of low socio-economic status has highlighted the existence of a confounding factor. In this work, we aim to study the effect of lysine deficiency on some inflammatory markers in the absence or presence of an inflammatory insult (lipopolysaccharide (LPS)). For this purpose, thirty-two 5-week-old male Sprague Dawley rats were randomly distributed into four groups: (1) control diet, (2) control diet+LPS, (3) lysine-deficient diet and (4) lysine-deficient diet + LPS. Groups were only allowed their experimental diets for 4 weeks, during which LPS (50 µg/kg) or saline injections were administered intraperitoneally three times per week. The study showed that lysine deficiency blunted growth and body compartments development, decreased albumin production and elevated liver C-reactive protein (CRP) expression, independently of IL-6 and IL-1ß, the main precursors of CRP. Also, the insufficient levels of lysine in the diet increased hyperactivity and triggered an anxiety-like behaviour, exacerbated with LPS. This work presents evidence that various physiological changes are associated with the absence of a sufficient amount of lysine in the diet and can potentially increase the risk factor for diseases. Thus, the increment in non-communicable disease among the low socio-economic status populations, who heavily rely on cereals as a main source of protein, can be, at least partially, blamed on low lysine availability in diets.

A test to measure oral iron absorption and glucose tolerance simultaneously in 18 to 55 year old premenopausal women.

BACKGROUND & AIMS: Several methods are available to measure iron absorption (IA). The oral iron absorption test (OIAT) measures IA based on a change in serum iron (ΔSeFe) concentration after an oral iron dose. The objective of this study was to validate the OIAT by comparing it to the reference method of fractional iron absorption (FIA) using red blood cell incorporation of stable iron isotopes from a labeled iron dose. A second objective was to assess whether the OIAT could be done simultaneously with an oral glucose tolerance test (OGTT), since iron deficiency and glucose intolerance may coexist, especially among overweight individuals with low-grade inflammation. METHODS: In this prospective experimental study, 116 women were enrolled and IA was measured using two different approaches 1) FIA from a labeled test meal containing 6 mg of 57Fe and 2) the OIAT assessing ΔSeFe at 2 h after the intake of 100 mg oral iron, done simultaneously with an OGTT. Markers of iron status, glycaemia and inflammation, and serum hepcidin, were measured. RESULTS: Prevalence of anemia and iron deficiency (defined as low serum ferritin) were 21% and 14%, respectively. ΔSeFe during the OIAT-OGTT was positively associated with FIA (r = 0.578, p < 0.001). ΔSeFe was not significantly correlated with markers of glucose and insulin metabolism during the OIAT-OGTT. CONCLUSIONS: The combined OIAT and OGTT method described here correlates well with FIA measured by stable iron isotopes, and could provide information on both IA and glucose tolerance in a single 2-h test, decreasing the burden on patients. clinicaltrials.gov (NCT03642223).

Urinary minerals excretion among primary schoolchildren in Dubai-United Arab Emirates.

INTRODUCTION: Urinary excretion of calcium (Ca), magnesium (Mg), phosphorus (P), iodine and fluoride is used to assess their statuses and/or the existence of metabolic abnormalities. In the United Arab Emirates (UAE), the urinary concentration of these minerals among children have not been documented. MATERIALS AND METHODS: A cross-sectional study, including 593 subjects (232 boys and 361 girls), was conducted among healthy 6 to 11-year-old Emirati children living in Dubai. Non-fasting morning urine samples and anthropometrical measurements were collected and analyzed. Results were expressed as per mg of creatinine (Cr). RESULTS: On average, estimated Cr excretion was 17.88±3.12 mg/kg/d. Mean urinary Ca/Cr, Mg/Cr and P/Cr excretions were 0.08±0.07 mg/mg, 0.09±0.04 mg/mg, and 0.57±0.26 mg/mg respectively. Urinary excretion of Ca, Mg and P were found to decrease as age increased. Urinary excretion and predicted intake of fluoride were lower than 0.05 mg/kg body weight per day. Surprisingly, more than 50% of the children were found to have urinary iodine excretion level above adequate. CONCLUSION: The Emirati schoolchildren had comparable levels of urinary Ca, Mg and P excretion to other countries. The 95% percentile allows the use of the current data as a reference value for the detection of mineral abnormalities. Fluoride excretion implies that Emirati children are at low risk of fluorosis. The level of urinary iodine excretion is slightly higher than recommended and requires close monitoring of the process of salt iodization to avoid the harmful impact of iodine overconsumption.

Iron Fortification and Supplementation: Fighting Anemia of Chronic Diseases or Fueling Obesity?

The significant worldwide increase in obesity has become a major health problem. Excess adiposity has been extensively linked to inflammation. Recently, studies have shown that dietary intake and microbiota dysbiosis can affect the health of the gut and lead to low-grade systemic inflammation, worsening the state of obesity and further exacerbating inflammation. The latter is shown to decrease iron status and potentially increase the risk of anemia by inhibiting iron absorption. Hence, anemia of obesity is independent of iron intake and does not properly respond to increased iron ingestion. Therefore, countries with a high rate of obesity should assess the health impact of fortification and supplementation with iron due to their potential drawbacks. This review tries to elucidate the relation between inflammation and iron status to better understand the etiology of anemia of obesity and chronic diseases and wisely design any dietary or medical interventions for the management of anemia and/or obesity.

Obesity and adiposity: the culprit of dietary protein efficacy.

Obesity and increased body adiposity have been alarmingly increasing over the past decades and have been linked to a rise in food intake. Many dietary restrictive approaches aiming at reducing weight have resulted in contradictory results. Additionally, some policies to reduce sugar or fat intake were not able to decrease the surge of obesity. This suggests that food intake is controlled by a physiological mechanism and that any behavioural change only leads to a short-term success. Several hypotheses have been postulated, and many of them have been rejected due to some limitations and exceptions. The present review aims at presenting a new theory behind the regulation of energy intake, therefore providing an eye-opening field for energy balance and a potential strategy for obesity management.

The effect of central obesity on inflammation, hepcidin, and iron metabolism in young women.

BACKGROUND/OBJECTIVES: In overweight and obesity (OW/OB), greater total body fat predicts higher serum hepcidin (SHep) which can impair iron homeostasis and increase risk for iron deficiency (ID). However, the effect of body fat distribution on SHep and iron homeostasis is unclear. In central obesity, interleukin (IL)-6 released from visceral adipose tissue into portal blood could strongly stimulate hepatic hepcidin synthesis. Thus, our hypothesis was that higher amounts of android fat, rather than gynoid fat, would predict impaired iron metabolism in OW/OB. SUBJECTS/METHODS: In this cross-sectional study, we enrolled 117 otherwise-healthy women into two groups: normal weight; BMI < 25 (n = 36) and OW/OB; BMI ≥ 25 (n = 81); we then subdivided the OW/OB using DEXA into tertiles based on the ratio of android fat/total body fat (AF/TBF). We measured inflammation and iron status, and assessed iron absorption in two ways: by measuring erythrocyte isotope incorporation from a labeled test meal containing 6 mg 57Fe (representing dietary iron); and by measuring change in serum iron (ΔSeFe) after a 100 mg oral iron challenge (representing supplemental iron). RESULTS: Greater AF/TBF correlated with higher CRP, AGP, SHep, and TIBC, and lower transferrin saturation and SeFe/SHep ratio (for all, p < 0.05). Greater AF/TBF correlated with lower supplemental iron absorption (ΔSeFe) (p = 0.08) but not lower dietary iron absorption. In multiple regressions, AF/TBF positively predicted CRP (p < 0.001) and SHep (p < 0.05); a model including AF/TBF and serum ferritin as covariates explained 65% of the variance in SHep. AF/TBF negatively predicted TSAT (p < 0.05) and iron absorption (ΔSeFe) (p = 0.07). In contrast, the ratio of gynoid fat/total body fat was not significantly associated with these variables. CONCLUSION: Body fat distribution affects iron metabolism: women with greater central adiposity have higher SHep, greater impairments in iron homeostasis, and reduced iron absorption from a supplemental iron dose.

The Effect of the Temperature of Plain or Sweetened Water on Body Composition in Rats.

INTRODUCTION: Humans are known to adapt to external temperature variations by altering energy intake, expenditure, and body fat storage for insulation [1, 2]. However, it is not clear whether the temperature of ingested water would induce such effects. Similarly, the involvement of the temperature of the ingested beverage has not been addressed in terms of body weight changes [3]. OBJECTIVES: This study was to investigate the effect of the ingestion of plain or sweetened water with varied temperatures on growth measures of rats. METHODS: Approval was obtained from the Institutional Animal Care and Use Committee of the American University of Beirut. After a 1-week adaptation period, 5- to 6-week-old male Sprague-Dawley rats were randomly divided into their respective experimental groups, housed individually (22 ± 1°C, reverse light cycle 12:12 h dark/light, light off at 10:00 a.m.) with free access to food and beverage for 8 weeks. Experiment 1 (Plain Water): Two groups of rats (n = 9) consumed room-temperature [∼22°C] (NW) or cold [∼5°C] (CW) water. Experiment 2 (Sweetened Water): Four groups of rats were offered sweetened water for 12 h, followed by plain water; (1) 10% sucrose + cold temperature (CS, n = 7), (2) 10% sucrose + room temperature (NS, n = 8), (3) 0.05% acesulfame K + cold temperature (CA, n = 7), and 4) 0.05% acesulfame K + room temperature (NA, n = 8). Food and beverage intake, body weight, and body composition were monitored using NMR minispec (LF110 Body Composition Analyzer, Bruker, USA) and energy expenditure was calculated based on the equation developed by Ravussin et al. [4]. Significance was set at a p value <0.05. RESULTS: Experiment 1: Body weight changes were similar between groups (Fig. 1-Exp 1a). In the CW group, lean body mass (%) was significantly higher, while body fat (%) was lower than the NW (Fig. 1-Exp 1b, c). These changes may relate to the calculated total energy expenditure [NW: 66.73 ± 4.49 kcal/day and CW: 73.75 ± 3.92 kcal/day) (p value = 0.003) since energy intake (NW: 89.97 ± 7.63 kcal/day vs. CW: 93.29 ± 6.26 kcal/day, p value = 0.329) was similar between groups. Experiment 2: Body weight of the CA group was higher than that of the other groups (Fig. 1-Exp 2a). Lean body mass (%) of the sucrose-sweetened water groups (Fig. 1-Exp 2b, c) was significantly higher, while body fat (%) was lower than that of the non-caloric sweetened water groups; these were not affected by the temperature of the beverage. Those variations are mostly explained by the differences in energy expenditure (p value temperature × sweetener = 0.015), as energy intake was not significantly different between groups. CONCLUSION: Cold plain water decreased body fat and increased lean body mass with no effect on total body weight. Sucrose-sweetened water had a better impact on body composition irrespective of the temperature of the beverage. The beneficial effects are mainly due to increased energy expenditure rather than variations in energy intake. Thus, the energy cost of warming the water seems to have been derived from an increase in fat oxidation.

Concomitant lysine and phosphorus addition to a wheat gluten protein diet highly amplified growth measures of rats.

OBJECTIVE: In humans, the effects of lysine-fortified wheat on growth measures was much lower than that of animal experimentations that used phosphorus-containing mineral mix. It is known that wheat contains a limited amount of available phosphorus, which is believed to support growth. The aim of this study was to determine the involvement of phosphorus in growth measures of rats maintained on a lysine-supplemented wheat gluten diet. METHODS: Forty male Sprague-Dawley (6 wk old) rats were randomly divided into four equal groups and fed wheat gluten protein (10%)-based diets with added lysine (0.6%), phosphorus (0.3%), or both (0.6% lysine and 0.3% phosphorus), ad libitum for 9 wk. Rats were monitored for changes in food intake, body weight, body and liver compositions, plasma urea nitrogen, and albumin. RESULTS: The addition of lysine or phosphorus to wheat gluten-based diets increased energy intake modestly (∼15%), whereas their combination caused a higher increase (∼45%). Similarly, the magnitude of improvement in weight gain and energy efficiency by the addition of lysine or phosphorus (∼1g/d and 2.7g/MJ, respectively) was much lower than that of the combination (∼4g/d and 8.7g/MJ). In the phosphorus-containing groups, plasma urea nitrogen was significantly reduced and this was associated with higher body protein (%) and hepatic fat (%); whereas plasma albumin was significantly increased in the lysine-containing groups. CONCLUSION: When using gluten protein, concomitant lysine and phosphorus availability is required to support growth measures, although phosphorus seems to have an independent effect on protein metabolism. Thus, human interventions should consider the improvement of the amino acid profile and phosphorus availability.

Phosphorus ingestion with a high-carbohydrate meal increased the postprandial energy expenditure of obese and lean individuals.

OBJECTIVES: Phosphorus ingestion with glucose was reported to stimulate the postprandial peripheral uptake of both phosphorus and glucose, a process that favors energy production. The aim of this study was to determine whether phosphorus ingestion with a meal can affect energy metabolism. METHODS: Overnight fasted men (eight lean and seven obese) consumed a high-carbohydrate meal (648 kcal) with either placebo or phosphorus (500 mg) tablets in a random order. Energy expenditure and substrate oxidation were monitored for 240 min using ventilated hood indirect calorimetry. RESULTS: Phosphorus ingestion with a meal increased the postprandial energy expenditure of both lean and obese individuals (P < 0.001), although in different patterns. Alterations in postprandial substrate oxidation was highly noticeable from time 120 min onward, where phosphorus-treated lean participants exhibited a significant decrease in respiratory quotient. CONCLUSION: Phosphorus ingestion with a high-carbohydrate meal alters postprandial energy metabolism mainly by enhancing postprandial energy expenditure that may ultimatly favor weight loss.

Metabolic syndrome among adolescents in Dubai, United Arab Emirates, is attributable to the high prevalence of low HDL levels: a cross-sectional study.

BACKGROUND: Metabolic syndrome (MetS) describes a combination of risk factors that increase the risk of developing chronic diseases. The prevalences of MetS and its risk factors are increasing, especially in the Arab region. A cross-sectional study was carried out to assess the prevalences of MetS and its associated risk factors among adolescents in the United Arab Emirates (UAE). METHODS: A total of 596 students (308 boys and 288 girls) aged 10 to 15.9 years old were recruited from 14 public secondary schools in Dubai, UAE. Anthropometric and biochemical data were measured. RESULTS: According to the International Diabetes Federation (IDF) criteria, the prevalence of MetS was 3.7%, and it was more common among boys than girls (12 boys versus 10 girls). MetS was also more likely to be found in students who were obese or overweight than those with normal weight. The most prevalent and significant MetS risk factor was low high-density lipoprotein (HDL) cholesterol levels. CONCLUSIONS: This study indicates the importance of carrying out further investigations about the constituents of HDL and their atherogenic effects. Additionally, these results strongly recommend setting a consensus for HDL measurement, since small variations in methodologies may lead to substantial deviations in results.

Impact of Pre-Processed Chickpea Flour Incorporation into "Mankoushe" on Appetite Hormones and Scores.

Recently, there has been an increasing interest in integrating pulse flours into pastries and baked products to improve their nutritional and health benefits. "Mankoushe," a popular Lebanese pastry made up of refined wheat flour was enriched with chickpea flour that is of better nutritional value, and its postprandial glycemia, insulinemia, lipidemia and appetite measures were monitored. A randomized cross-over study was performed on sixteen healthy Lebanese females, age (years): 22.90 ± 3.00, and BMI (kg/m²): 22.70 ± 2.65. Over-night fasted females were asked to consume two iso-energetic meals (201 g; 681 kcal) on two separate days, three days apart. One meal was the "Regular Mankoushe" (RM) made with white flour 100%, and the second meal was the "Chickpeas Mankoushe" (CM) made with a mixture of wheat/chickpea flour (70/30). Blood samples were collected 15 min before meal ingest and at 30, 90, 150 and 210 min postprandial. Glucose, insulin, triglycerides (TG), ghrelin, and glucagon-like peptide 1 (GLP-1) plasma levels were measured. Subjective appetite rating and food intake were also assessed. Incorporation of pre-processed chickpea flour into "Mankoushe" as 30% of the dough was associated with a modest reduction in both glucose and insulin levels, and TG was minimally affected. At the level of appetite hormones, changes in GLP-1 were similar, whereas the reduction in ghrelin was significantly lower after the RM meal and thus favored a higher satiating effect compared to CM. This was not paralleled by a similar change in subjective appetite scores and subsequent energy intake. In conclusion, findings suggest that pre-processed chickpea flour could be a promising functional ingredient of traditional pastries to improve their nutritional quality. Nevertheless, further investigations are warranted regarding its satiating effect.

Elevated urinary Na/K ratio among Lebanese elementary school children is attributable to low K intake.

PURPOSE: To estimate total sodium (Na) and potassium (K) intake using non-fasting morning urine specimens among Lebanese elementary (6-10 year old) schoolchildren. METHOD: A national cross-sectional study was conducted. A multistage cluster sampling procedure was used to select a representative sample of 1403 healthy children from the eight districts of Lebanon. Age, anthropometric measurements, and urine samples were collected and analyzed for Na, K, and creatinine (Cr). RESULTS: The ratios of Na and K to Cr were 23.93 ± 15.54 mM/mM (4.86 ± 3.16 mg/mg) and 11.48 ± 5.82 mM/mM (3.97 ± 2.01 mg/mg), respectively, and showed differences (P value <0.001) between age groups. No differences were found between boys and girls in all the measured Na and K parameters. The estimated mean Na intake was 96.57 ± 61.67 mM/day (2.220 ± 1.418 g/day or 5.69 ± 3.64 g NaCl/day) and exceeded the upper limit of intake in half the children. Estimated K intake was 46.6 ± 23.02 mM/day (1.822 ± 0.900 g/day), and almost all children failed to meet the recommended daily K intake. The high Na/K ratio (2.361 ± 1.67 mM/mM or 1.39 ± 0.98 mg/mg) resulted from a combination of high Na and low K intake but was mostly affected by K intake. CONCLUSIONS: About 50 % of children exceeded the recommended daily upper intake for Na, while the majority was below K adequate intake. This unfavorable Na/K ratio is indicative of potentially negative health effects at later stages in life. Interventions aimed at reducing salt intake and increasing consumption of fruits and vegetables are warranted.

Lebanese children are iodine deficient and urinary sodium and fluoride excretion are weak positive predictors of urinary iodine.

PURPOSE: To assess iodine and fluoride status among Lebanese children. METHODS: A nationally representative cross-sectional study of 6- to 10-year-old schoolchildren was conducted using multistage cluster sampling. Spot urine samples were collected from 1403 children, and urinary iodine, fluoride, creatinine and sodium levels were measured. Salt samples from markets (n = 30) were tested for iodine concentration by titration. RESULTS: Median urinary iodine concentration was 66.0 µg/l, indicating mild deficiency, and almost 75 % of Lebanese children had a urinary iodine concentration (UIC) <100 µg/l. UIC was higher among children from private schools and in areas of higher socioeconomic status. Most salt samples were fortified at levels far below the legislated requirement, and 56 % of samples contained less than 15 ppm iodine. Fluoride-to-creatinine ratio (F/Cr) was 0.250 (0.159-0.448) mg/g. There were weak positive correlations between UIC and urinary sodium (r 2 = 0.039, P value <0.001) and UIC and urinary fluoride (r 2 = 0.009, P value <0.001). CONCLUSIONS: Lebanese elementary school children are iodine deficient due to inadequately iodized salt. The weak correlation between UIC and urinary sodium suggests most dietary iodine does not come from iodized salt. The poor correlation between UIC and urinary fluoride suggests that fluoride intake is not affecting iodine metabolism. Efforts are needed in Lebanon to improve industry compliance with salt fortification through improved monitoring and enforcement of legislation.

Urinary Magnesium, Calcium, and Phosphorus to Creatinine Ratios of Healthy Elementary School Lebanese Children.

Urinary magnesium (Mg), calcium (Ca), and phosphorus (P) excretions are known to vary greatly between populations due to dietary habits, physical activity, mineral content of water, climate, genetics, and race. Thus, it is essential to determine the normal values in each population in order to assess the status as well as to diagnose any possible abnormality of metabolisms especially hypercalciuria. A study was conducted to determine urinary Mg/creatinine (Cr), Ca/Cr, and P/Cr ratios of healthy Lebanese elementary schoolchildren. Using a multi-stage cluster sampling at district, school, and class levels, a sample of 1403 children (781 boys and 622 girls), from 26 different schools, was selected. Non-fasting morning urine samples and anthropometric data were collected and analyzed. The mean Mg/Cr, Ca/Cr, and P/Cr ratios were 0.122 ± 0.075 mg/mg (0.568 ± 0.348 mM/mM), 0.084 ± 0.101 mg/mg (0.237 ± 0.286 mM/mM), and 0.692 ± 0.417 mg/mg (2.527 ± 1.524 mM/mM), respectively, with no significant difference between boys and girls (P = 0.706, 0.161, and 0.604; respectively). The 95th percentile of Mg/Cr, Ca/Cr, and P/Cr ratios fluctuated with age, showing a sharp decrease in Ca/Cr and P/Cr at the age of 10. The mean Mg/Cr, Ca/Cr, and P/Cr ratios were comparable to those of similar age groups in other populations. The 95th percentiles of Mg/Cr, Ca/Cr, and P/Cr ratios were 0.26 mg/mg (1.23 mM/mM), 0.27 mg/mg (0.76 mM/mM), and 1.48 mg/mg (5.40 mM/mM), respectively. These values can be used as cutoffs to detect abnormalities in these three minerals' metabolisms among healthy Lebanese children.