Long-term effects of dietary glycemic index on adiposity, energy metabolism, and physical activity in mice

A high-glycemic index (GI) diet has been shown to increase adiposity in rodents; however, the long-term metabolic effects of a low- and high-GI diet have not been examined. In this study, a total of 48 male 129SvPas mice were fed diets high in either rapidly absorbed carbohydrate (RAC; high GI) or slowly absorbed carbohydrate (SAC; low GI) for up to 40 wk. Diets were controlled for macronutrient and micronutrient content, differing only in starch type. Body composition and insulin sensitivity were measured longitudinally by DEXA scan and oral glucose tolerance test, respectively. Food intake, respiratory quotient, physical activity, and energy expenditure were assessed using metabolic cages. Despite having similar mean body weights, mice fed the RAC diet had 40% greater body fat by the end of the study and a mean 2.2-fold greater insulin resistance compared with mice fed the SAC diet. Respiratory quotient was higher in the RAC group, indicating comparatively less fat oxidation. Although no differences in energy expenditure were observed throughout the study, total physical activity was 45% higher for the SAC-fed mice after 38 wk of feeding. We conclude that, in this animal model, 1) the effect of GI on body composition is mediated by changes in substrate oxidation, not energy intake; 2) a high-GI diet causes insulin resistance; and 3) dietary composition can affect physical activity level.     

Effects of polymorphisms in nucleotide-binding oligomerization domains 1 and 2 on biomarkers of the metabolic syndrome and type II diabetes

The innate immune receptor toll-like receptor 4 (TLR4) has been implicated in mediating some of the effects of dietary lipids on inflammation and type 2 diabetes (T2D). Similar to TLR4, the nucleotide-binding oligomerization domains (Nods) 1 and 2 are also proteins of innate immunity, which can respond to lipids and initiate pro-inflammatory signalling that plays a role in the aetiology of T2D. The objective was to determine the effect of Nod1 (Glu266Lys) and Nod2 (Ser268Pro) genotypes on factors associated with the metabolic syndrome (MetS), and whether they modify the association between dietary lipids and biomarkers of the MetS. Men and women (n = 998) between the ages of 20–29 years were genotyped for both polymorphisms, completed a one-month, semiquantitative food frequency questionnaire and provided a fasting blood sample. The Glu266Lys polymorphism in Nod1 was not associated with any of the biomarkers of the MetS, but modified the association between dietary saturated fat (SFA) and insulin sensitivity, as measured by HOMA-IR (p for interaction = 0.04). Individuals with the Glu/Glu or Glu/Lys genotype showed no significant relationship between dietary SFA and HOMA-IR (β = −0.002 ± 0.006, p = 0.77; and β = −0.003 ± 0.006, p = 0.61), while those with the Lys/Lys genotype showed a positive association (β = 0.033 ± 0.02, p = 0.03). The Nod2 Ser268Pro polymorphism was not associated with components of the MetS and did not modify the relationship between dietary lipid intake and the biomarkers of MetS. In summary, the Nod1 Glu266Lys polymorphism modifies the relationship between dietary SFA intake and HOMA-IR, suggesting that Nod1 may act as an intracellular lipid sensor affecting insulin sensitivity.     

PTGS1, PTGS2, ALOX5, ALOX12, ALOX15, and FLAP SNPs: interaction with fatty acids in colon cancer and rectal cancer

Dietary polyunsaturated fatty acids (PUFAs) can be converted to prostaglandins and leukotrienes. Oxygenation of omega-6 PUFAs generally results in the production of pro-inflammatory mediators, whereas oxygenated products of omega-3 (n-3) PUFAs generally have lower inflammatory activity. We hypothesize that elevated n-3 PUFA intakes from fish are associated with lower risk of colorectal cancer among those with genetic variants that result in higher levels of pro-inflammatory mediators. In population-based case–control studies of colon (case n = 1,574) and rectal cancer (case n = 791) and disease-free controls (n = 2,969), we investigated interactions between dietary fatty acid intake and 107 candidate polymorphisms and tagSNPs in PTGS1, PTGS2, ALOX12, ALOX5, ALOX15, and FLAP. The two studies used an identical genotyping protocol. We observed interactions and statistically significant increases in colon cancer risk for low docosahexaenoic acid intake among those with the PTGS1 rs10306110 (−1,053 A > G) variant genotypes (OR = 1.6, 95 % confidence interval = 1.1–2.3, adj. p = 0.06) and rectal cancer risk for low total fat intake among those with the variant PTGS1 rs10306122 (7,135 A > G) (OR_vs.wt = 1.80, 1.02–2.99; adj. p = 0.08). The ALOX15 rs11568131 (10,339 C > T) wild type in combination with a high inflammation score (low EPA intake, high AA intake, no regular NSAID use, high BMI, smoking) was associated with increased colon cancer risk (OR = 2.28, 1.7–3.07). Rectal cancer risk was inversely associated with a low inflammation score among PTGS2 rs4648276 (3,934 T > C) variant allele carriers (OR = 0.49, 0.25–0.75). Overall, these data provide some modest evidence for interactions between dietary fat intake and genetic variation in genes involved in eicosanoid metabolism and colorectal cancer risk.

Electronic supplementary material

The online version of this article (doi:10.1007/s12263-012-0302-x) contains supplementary material, which is available to authorized users.     

Genetic predisposition to type 2 diabetes is associated with impaired insulin secretion but does not modify insulin resistance or secretion in response to an intervention to lower dietary saturated fat

Genome-wide association studies have identified SNPs reproducibly associated with type 2 diabetes (T2D). We examined the effect of genetic predisposition to T2D on insulin sensitivity and secretion using detailed phenotyping in overweight individuals with no diagnosis of T2D. Furthermore, we investigated whether this genetic predisposition modifies the responses in beta-cell function and insulin sensitivity to a 24-week dietary intervention. We genotyped 25 T2D-associated SNPs in 377 white participants from the RISCK study. Participants underwent an IVGTT prior to and following a dietary intervention that aimed to lower saturated fat intake by replacement with monounsaturated fat or carbohydrate. We composed a genetic predisposition score (T2D-GPS) by summing the T2D risk-increasing alleles of the 25 SNPs and tested for association with insulin secretion and sensitivity at baseline, and with the change in response to the dietary intervention. At baseline, a higher T2D-GPS was associated with lower acute insulin secretion (AIRg 4% lower/risk allele, P = 0.006) and lower insulin secretion for a given level of insulin sensitivity, assessed by the disposition index (DI 5% lower/risk allele, P = 0.002), but not with insulin sensitivity (Si). T2D-GPS did not modify changes in insulin secretion, insulin sensitivity or the disposition index in response to the dietary interventions to lower saturated fat. Participants genetically predisposed to T2D have an impaired ability to compensate for peripheral insulin resistance with insulin secretion at baseline, but this does not modify the response to a reduction in dietary saturated fat through iso-energetic replacement with carbohydrate or monounsaturated fat.

Electronic supplementary material

The online version of this article (doi:10.1007/s12263-012-0284-8) contains supplementary material, which is available to authorized users.     

Impact of tannic acid on blood pressure,oxidative stress and urinary parameters in L-NNA-induced hypertensive rats

Hypertension is a major health problem with increasing prevalence around the world. Tannic acid is water-soluble polyphenol that is present in tea, green tea, coffee, red wine, nuts, fruits and many plant foods. It has been reported to serve as an antioxidant or a pro-oxidant depending on the type of cells and its concentration. The purpose of our study was to evaluate the effect of tannic acid on systolic blood pressure, oxidative stress and some urinary parameters in the rat model of essential hypertension. Blood pressures of all rats were measured using the tail-cuff method. The nitric oxide synthase inhibitor N (omega)-nitro-L-arginine was administered orally at a dose of 0.5 g/l/day for 15 days to rats in order to create an animal model of hypertension. Tannic acid was intraperitoneally injected at a dose of 50 mg/kg for 15 days. Superoxide dismutase, catalase activity and the concentration of malondialdehyde (MDA) were determined in blood plasma and homogenates of heart, liver and kidney. In order to evaluate renal functions, urine pH, urine volume, urine creatine, uric acid, and urea nitrogen values were measured. Compared with the hypertension group, a decrease in MDA concentrations of heart tissue (p < 0.01), urea nitrogen values (p < 0.01) and urine volumes (p < 0.001) were established in hypertension + tannic acid group. There was also a decrease in blood pressure values (20th and 30th days) of this group, but there was no a statistical difference according to hypertension group. The findings of our research show the effect of tannic acid in lowering blood pressure in hypertensive rats.     

Polymorphisms in LEP and NPY genes modify the response to soluble fibre Plantago ovata husk intake on cardiovascular risk biomarkers

The satiating effect of fibre consumption has been related to gut hormones, such as peptide YY and leptin. These peptides may also influence cardiovascular (CVD) risk biomarkers. Nevertheless, there is wide interindividual variation in metabolic responses to fibre consumption. The objective was to investigate differences in the effects of soluble fibre, in the form of Plantago ovata husk (Po-husk) treatment, on CVD risk biomarkers according to selected polymorphisms in genes related to satiety. The study was a multi-centred, double-blind, placebo-controlled, parallel and randomised trial in mild–moderate hypercholesterolaemic patients (age range: 43–67 years). Eight polymorphisms in three genes related to satiety (LEP, NPY and PYY) were identified in 178 participants; 88 patients in the placebo (microcrystalline cellulose 14 g/day) group and 90 in the Po-husk (14 g/day) group, which had added to a low-saturated-fat diet for 8 weeks. The CVD biomarkers measured included the following: lipid profile, blood pressure (BP), glucose, insulin, hs-CRP, oxidised LDL and IL-6. Relative to the placebo, Po-husk consumption lowered the plasma total cholesterol concentration by 3.3 % according to rs7799039 polymorphism in the LEP gene (p < 0.05). Furthermore, the Po-husk reduced systolic BP (mean [95 % CI]) by −8 mmHg (−14.16; −1.90) and hs-CRP by 24.9 % in subjects with the AA genotype of the rs16147 polymorphism in the NPY gene (32 % of our total population; p < 0.05), which remained significant after Bonferroni correction. In conclusion, polymorphisms in the LEP and NPY genes potentiate the response to Po-husk, particularly the effects on systolic BP and the hs-CRP plasma concentration.     

Validation and Assessment of Three Methods to Estimate 24-h Urinary Sodium Excretion from Spot Urine Samples in Chinese Adults

24-h urinary sodium excretion is the gold standard for evaluating dietary sodium intake, but it is often not feasible in large epidemiological studies due to high participant burden and cost. Three methods—Kawasaki, INTERSALT, and Tanaka—have been proposed to estimate 24-h urinary sodium excretion from a spot urine sample, but these methods have not been validated in the general Chinese population. This aim of this study was to assess the validity of three methods for estimating 24-h urinary sodium excretion using spot urine samples against measured 24-h urinary sodium excretion in a Chinese sample population. Data are from a substudy of the Prospective Urban Rural Epidemiology (PURE) study that enrolled 120 participants aged 35 to 70 years and collected their morning fasting urine and 24-h urine specimens. Bias calculations (estimated values minus measured values) and Bland-Altman plots were used to assess the validity of the three estimation methods. 116 participants were included in the final analysis. Mean bias for the Kawasaki method was -740 mg/day (95% CI: -1219, 262 mg/day), and was the lowest among the three methods. Mean bias for the Tanaka method was -2305 mg/day (95% CI: -2735, 1875 mg/day). Mean bias for the INTERSALT method was -2797 mg/day (95% CI: -3245, 2349 mg/day), and was the highest of the three methods. Bland-Altman plots indicated that all three methods underestimated 24-h urinary sodium excretion. The Kawasaki, INTERSALT and Tanaka methods for estimation of 24-h urinary sodium excretion using spot urines all underestimated true 24-h urinary sodium excretion in this sample of Chinese adults. Among the three methods, the Kawasaki method was least biased, but was still relatively inaccurate. A more accurate method is needed to estimate the 24-h urinary sodium excretion from spot urine for assessment of dietary sodium intake in China.     

Effects of a dietary organic acid mixture and of dietary fibre levels on ileal and faecal nutrient apparent digestibility, bacterial nitrogen flow, microbial metabolite concentrations and rate of passage in the digestive tract of pigs

Six 34-kg barrows were fitted with a post-valve T-caecum cannula and assigned to six dietary treatments according to a 6 × 5 change-over design to study how a mixture of formic acid, sorbate, and benzoate (0 or 8.4 g/kg feed) influences apparent ileal and faecal digestibility coefficients, bacterial nitrogen (N) flow, microbial metabolite concentrations, and passage rate in pigs fed isoenergetic diets with medium, high, or very high fibre content (neutral-detergent fibre (NDF): 199, 224, and 248 g/kg dry matter, respectively). These barley and soya-bean meal based diets contained 0, 75, and 150 g/kg barley fibre (NDF: 577 g/kg) and 0, 8, and 16 g/kg rapeseed oil, respectively. The dietary organic acid mixture improved the apparent ileal digestibility of 14 of the 17 amino acids analysed (P < 0.05). Increasing levels of dietary fibre linearly decreased the apparent ileal digestibility of six of the 17 amino acids analysed (P < 0.05). Ileal flows of bacterial N and amino acids as assessed on the basis of purine flow were decreased by the dietary organic acid mixture (P < 0.05) but were not affected by dietary fibre level (P>0.05). As assessed on the basis of diaminopimelic acid flow, bacterial N flow was increased by both the dietary organic acid mixture and increased dietary fibre levels (P < 0.05). The dietary organic acid mixture reduced the concentration of lactic acid and increased that of acetic acid in ileal digesta (P < 0.05), while dietary fibre levels had a quadratic effect on concentrations of acetic, propionic, and butyric acid (P < 0.05). The mean retention time of Co (solute marker) and Yb (particle marker) in the large intestine decreased in a linear manner by increasing dietary fibre levels (P < 0.05) but was not affected by the dietary organic acid mixture (P>0.05). The results show that a dietary organic acid mixture has a positive effect on the apparent ileal digestibility of most amino acids irrespective of dietary fibre levels. This could be at least partly related to changes in bacterial N flow in the ileum. However, different bacterial markers showed opposite effects on bacterial N flow, which makes it questionable to use a constant bacterial marker / bacterial N ratio to estimate bacterial N flow. Increasing levels of dietary fibre had negative effects on the apparent ileal amino acid digestibilities and shortened the mean retention time of digesta in the large intestine.     

The -308 G/A polymorphism of the tumour necrosis factor-α gene modifies the association between saturated fat intake and serum total cholesterol levels in white South African women

This study explored interactions between dietary fat intake and the tumour necrosis factor-α gene (TNFA) -308 G/A polymorphism on serum lipids in white South African (SA) women. Normal-weight (N = 88) and obese (N = 60) white SA women underwent measurements of body composition, fat distribution, fasting serum lipids, glucose, insulin concentrations and dietary intake. Subjects were genotyped for the functional -308 G/A polymorphism within the TNFA gene. There were no significant differences in the genotype or allele frequencies between groups, and no significant genotype associations were found for body fatness or distribution, or serum lipid concentrations. However, there was a significant interaction effect between dietary saturated fat (SFA) intake (%E) and TNFA -308 genotypes on serum total cholesterol concentrations (P = 0.047). With increasing SFA intake (%E), serum total cholesterol levels decreased for the GG genotype and increased for the GA plus AA genotypes. The TNFA -308 G/A polymorphism appears to modify the relationship between dietary fat intake and serum total cholesterol concentrations in white SA women.     

A randomized trial of genetic information for personalized nutrition

Personal genetic information has become increasingly accessible to the public as a result of direct-to-consumer (DTC) genetic tests; however, concerns have been raised over their value and potential risks. We compared the effects of providing genotype-based dietary advice with general recommendations on behavioral outcomes using a randomized controlled study. Participants were men and women from the Toronto Nutrigenomics and Health Study between the ages of 20–35 years (n = 149) who completed a survey to assess their awareness of DTC genetic tests and nutrigenomics, as well as potential motivations for undergoing genetic testing. Participants were then randomized into an intervention (I) or control (C) group and were given either genotype-based personalized dietary advice or general dietary advice, respectively. A second survey was administered to assess the participants’ opinions of the dietary reports they received. A greater proportion of participants in the intervention group agreed that they understood the dietary advice they were given (93% (I) vs. 78% (C); p = 0.009). Participants in the intervention group were more likely to agree that the dietary recommendations they received would be useful when considering their diet (88% (I) vs. 72% (C); p = 0.02) and wanted to know more about the recommendations (95% (I) vs. 76% (C); p < 0.0001). Only 9% of participants in the intervention group reported feeling uneasy about learning their genetic information. These findings suggest that individuals find dietary recommendations based on genetics more understandable and more useful than general dietary advice. Very few feel uneasy about receiving their genetic information that relates to personalized nutrition.     

Effects of Three Commonly-used Diuretics on the Urinary Proteome

bstract Biomarker is the measurable change associated with a physiological or pathophysiological process. Unlike blood which has mechanisms to keep the internal environment homeostatic,rine is more likely to reflect changes of the body. As a result, urine is likely to be a better biomarker ource than blood. However, since the urinary proteome is affected by many factors, including iuretics, careful evaluation of those effects is necessary if urinary proteomics is used for biomarker iscovery. Here, we evaluated the effects of three commonly-used diuretics(furosemide, F; hydrochlorothiazide,H; and spirolactone, S) on the urinary proteome in rats. Urine samples were collected before and after intragastric administration of diuretics at therapeutic doses and the roteomes were analyzed using label-free liquid chromatography–tandem mass spectrometry LC–MS/MS). Based on the criteria of P 6 0.05, a fold change P2, a spectral count P5, and false ositive rate(FDR) 61%, 14 proteins(seven for F, five for H, and two for S) were identified by rogenesis LC–MS. The human orthologs of most of these 14 proteins are stable in the healthy uman urinary proteome, and ten of them are reported as disease biomarkers. Thus, our results uggest that the effects of diuretics deserve more attention in future urinary protein biomarker tudies. Moreover, the distinct effects of diuretics on the urinary proteome may provide clues to     

Effect of dietary protein intake on plasma leucine flux, protein synthesis, and degradation in sheep

Combined experiments of an isotope dilution method of [1-(13)C]leucine with open circuit calorimetry and a nitrogen (N) balance test were applied to determine the effect of dietary crude protein (CP) intake on plasma leucine flux and protein synthesis and degradation in four sheep. The experiment was conducted in a 3 x 4 Latin rectangle design of three 3-week periods. Dietary CP intake was 5.6, 7.7, and 10.8 g/(kg(0.75) x d). Metabolizable energy intake was 120% of requirement for all dietary treatments. [1-(13)C]Leucine was intravenously infused for 8 h and blood and breath samples were collected during the latter 2-h period of infusion. Isotopic enrichments of plasma [1-(13)C]leucine, alpha-[1-(13)C]ketoisocaproic acid, and exhaled (13)CO(2) were determined. For the N balance test, N digestibility, N excretion in urine, and protein balance (N x 6.25) increased with increasing dietary CP intake. Rates of plasma leucine turnover, protein synthesis, and degradation changed toward reduction with increased dietary CP intake. It is likely that in sheep, high CP intake enhances protein deposition with reduced protein degradation rather than increased protein synthesis.     

APOB-516 T allele homozygous subjects are unresponsive to dietary changes in a three-month primary intervention study targeted to reduce fat intake

Dietary guidelines aim to control fat intake and reduce cardiovascular risk but an important interindividual variability occurs among subjects. The objective was to investigate whether the response of lipid and glucose homeostasis parameters after a three-month diet aimed at reducing cardiovascular risk could be modulated by the −516C/T polymorphism in the apolipoprotein B gene (APOB). Middle-aged men (n = 69) and women (n = 100) with moderate cardiovascular disease risk were advised to reduce total energy and fat intakes and replace saturated dietary fat by monounsaturated and polyunsaturated fat. Subjects were genotyped for APOB-516C/T polymorphism. At the entry and at the end of the three-month period, fasting and postprandial plasma lipid analyses were performed. At entry, subjects homozygous for the APOB-516 T allele exhibited significantly lower fasting plasma concentrations of apolipoprotein B 48, triglycerides and triglyceride-rich lipoproteins-triglycerides compared to C carrier subjects. After the diet period, while C carrier subjects presented a clear improvement of most biological parameters, paradoxically T/T subjects did not modify them. In addition, the apoB 48 postprandial response after a standardized mixed test meal was not improved in T/T subjects after the three-month diet, contrary to C allele carriers. Even though their phenotype at entry does not show any significant increase of risk factors when compared to other groups, subjects homozygous for the APOB-516 T allele are unresponsive to a healthy diet that improves cardiovascular risk status in the whole population.     

Effect of a moderate variation in dietary energy intake on the retention and excretion of zinc,calcium, and magnesium

Mineral balance was studied by metabolic balance techniques in 13 healthy college females aged 21–23 yr. They were fed diet containing 1780 kcal, 2580 kcal, and 25 g protein in a 20-d experiment period. Both diets contained approximately 5.28 mg zinc, 216.85 mg calcium, and 364.3 mg magnesium. The diet consisted of habitually consumed foods. Blood, urine and fecal samples were collected for mineral analysis using atomic absorption spectrophotometry. Plasma mineral levels were not affected by the change in dietary energy intake. Fecal calcium and magnesium were significantly higher when subjects were fed the low calorie (1780 kcal) diet, whereas there was no significant difference in fecal zinc for the two levels of dietary energy. Urinary calcium and magnesium were also significantly higher when the diet provided 1780 kcal though, on the other hand, urinary zinc was significantly higher when the diet provided 2680 kcal (P<0.05). Urinary calcium and magnesium correlated negatively, whereas urinary zinc correlated positively, with the dietary energy intake (P ^o<0.05). Dietary energy intake has a significant effect on the mineral balance of the subjects.     

Blood profile of proteins and steroid hormones predicts weight change after weight loss with interactions of dietary protein level and glycemic index

Background

Weight regain after weight loss is common. In the Diogenes dietary intervention study, high protein and low glycemic index (GI) diet improved weight maintenance.

Objective

To identify blood predictors for weight change after weight loss following the dietary intervention within the Diogenes study.

Design

Blood samples were collected at baseline and after 8-week low caloric diet-induced weight loss from 48 women who continued to lose weight and 48 women who regained weight during subsequent 6-month dietary intervention period with 4 diets varying in protein and GI levels. Thirty-one proteins and 3 steroid hormones were measured.

Results

Angiotensin I converting enzyme (ACE) was the most important predictor. Its greater reduction during the 8-week weight loss was related to continued weight loss during the subsequent 6 months, identified by both Logistic Regression and Random Forests analyses. The prediction power of ACE was influenced by immunoproteins, particularly fibrinogen. Leptin, luteinizing hormone and some immunoproteins showed interactions with dietary protein level, while interleukin 8 showed interaction with GI level on the prediction of weight maintenance. A predictor panel of 15 variables enabled an optimal classification by Random Forests with an error rate of 24±1%. A logistic regression model with independent variables from 9 blood analytes had a prediction accuracy of 92%.

Conclusions

A selected panel of blood proteins/steroids can predict the weight change after weight loss. ACE may play an important role in weight maintenance. The interactions of blood factors with dietary components are important for personalized dietary advice after weight loss.

Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00390637","term_id":"NCT00390637"}}NCT00390637     

The Effect of Acid pH Modifiers on the Release Characteristics of Weakly Basic Drug from Hydrophlilic–Lipophilic Matrices

The solubility of weakly basic drugs within passage though GI tract leads to pH-dependent or even incomplete release of these drugs from extended release formulations and consequently to lower drug absorption and bioavailability. The aim of the study was to prepare and evaluate hydrophilic–lipophilic (hypromellose–montanglycol wax) matrix tablets ensuring the pH-independent delivery of the weakly basic drug verapamil-hydrochloride by an incorporation of three organic acidifiers (citric, fumaric, and itaconic acids) differing in their concentrations, pK_a, and solubility. The dissolution studies were performed by the method of changing pH values, which better corresponded to the real conditions in the GI tract (2 h at pH 1.2 and then 10 h at pH 6.8). Within the same conditions, pH of matrix microenvironment was measured. To determine relationships between the above mentioned properties of acidifiers and the monitored effects (the amount of released drug and surface pH of gel layer in selected time intervals—360 and 480 min), the full factorial design method and partial least squares PLS-2 regression were used. The incorporation of the tested pH modifiers significantly increased the drug release rate from matrices. PLS-components explained 75% and 73% variation in the X- and Y-data, respectively. The obtained results indicated that the main crucial points (p < 0.01) were the concentration and strength of acidifier incorporated into the matrix. Contrary, the acid solubility surprisingly did not influence the selected effects except for the surface pH of gel layer in time 480 min.Key words: gel layer, matrix tablets, pH-independent drug release, pH modifiers, statistical evaluation     

Cholesterol absorption status and fasting plasma cholesterol are modulated by the microsomal triacylglycerol transfer protein −493 G/T polymorphism and the usual diet in women

An important inter-individual variability in cholesterol absorption has been reported. It could result from polymorphisms in genes coding for proteins involved in the absorption process and in interaction with dietary intakes. To assess whether the extent of cholesterol absorption or synthesis is modified in adult women according to the −493 G/T polymorphism in the microsomal triglyceride transfer protein gene (MTP) and/or the habitual diet. Cholestanol and sitosterol, as well as desmosterol and lathosterol, surrogate markers of cholesterol absorption or synthesis, respectively, were analyzed in the fasting plasma of 69 middle-aged women under a Western-type diet (WD) and after 3 months on a low-saturated fat, low-cholesterol/Mediterranean-type diet (LFLCD). Genotypes for MTP −493G/T polymorphism were determined. Under an usual WD, subjects homozygous for the MTP −493 T allele exhibited higher (P < 0.05) fasting serum concentrations of cholestanol (199.0 ± 30.0 vs. 133 ± 7.4 × 10² mmol/mol cholesterol) and lathosterol (188.7 ± 21.8 vs. 147.6 ± 9.1 × 10² mmol/mol cholesterol), as well as total cholesterol (7.32 ± 0.22 vs. 6.63 ± 0.12 mmol/l) compared to G carrier subjects. After 3 months on a LFLCD, level of absorption markers decreased in TT subjects with no change in synthesis ones, leading to values comparable to those measured in G carriers. The lowering of plasma total and LDL cholesterol due to dietary change was 2.4- and 2.3-fold greater in TT women than in G carriers. The polymorphism −493G/T in MTP modulates the level of cholesterol absorption but not synthesis in women under a WD, an effect abolished under a prudent LFLCD.     

Heat shock protein 70 and albuminuria in patients with type 2 diabetes: a matched case control study

Here, we aimed to study serum heat shock protein (HSP) 70 levels in diabetic patients with and without albuminuria. We performed a 1:1 matched case control study on 40 diabetic patients with albuminuria as cases and 40 age, sex, body mass index matched diabetic patients without albuminuria (normoalbuminuria) as controls. Normoalbuminuria was defined as urinary albumin excretion rate <15 mg/12 h, and albuminuria was defined as urinary albumin excretion rate between 100–400 mg/12 h. Patients with albuminuria had a higher HSP70 than controls (0.83 ± 0.50 vs. 0.63 ± 0.06; p = 0.02), while they did not differ in any other studied variables. In ten of the studied pairs, the controls had higher HSP70 levels than cases (reverse relationship). Patients in the “direct relationship group” had higher HbA1c values than the patients in the “reverse relationship group” (8.9 ± 0.3 vs. 7.3 ± 0.6, p = 0.04). Cases in the reverse pairs had a lower low density lipoprotein cholesterol levels than their controls. The odds ratio of HSP70 in the prediction of albuminuria was (28.69 (3.2–250.1), p = 0.002). In conclusion, we have shown an increased HSP70 levels in diabetic patients with albuminuria.     

Multidrug-resistant Escherichia coli in Raw Milk: Molecular Characterization and the potential impact of camel’s Urine as an Antibacterial Agent

Raw milk is one of the most important vehicles for transmitting various pathogens, especially Escherichia coli (E. coli). Multidrug-resistant pathogens are highly prevalent among mastitic cows in various dairy farms worldwide. Therefore, our current study is based on the identification of E. coli from mastitic cow’s milk and their resistance to various antibacterial agents. As well, the impact of camel’s urine on multi-drug resistant E. coli were also evaluated. Thirty-three E. coli isolates were recovered from 254 milk samples. All strains were initially identified phenotypically by culturing on specific media and Vitek 2 Compact System. The protein fingerprinting technique was used as a confirmatory method. The Stx1, Stx2 and eae genes were also verified by polymerase chain reaction (PCR). The antimicrobial resistance of E. coli strains was tested by the Vitek 2 AST-GN69 cards. Thirty multi-drug resistant E. coli strains (20 from mastitic milk and 10 from clinical samples) were laboratory tested with different concentrations (100%, 75%, 50% and 25%) of virgin and breeding camel’s urine, using the paper disc diffusion method. Our findings showed that 93.94% of E. coli strains were recognized by the Vitek™ 2 system. The results of proteomic investigation illustrated that 100% of E. coli strains were identified at log values ≥2.00. The genotypic identification of the three virulence genes illustrated that 90.1%, 63.64%, and 30.55% of E. coli strains were able to carry the Stx1, eae, and Stx2 genes, respectively. Most strains of E. coli showed strong resistance against cefazolin (78.79%), ceftazidime (66.67%), cefotaxime (60.61%), ceftriaxone (54.55%), and cefepime (39.40%). The results of the antibacterial effect of camel’s urine revealed that the mean inhibitory zones of virgin camel’s urine were 28 mm, 17 mm, and 14 mm, for the concentrations of 100%, 75%, and 50%, respectively. Whereas; the inhibitory zones for the breeding camel’s urine were 18 mm, 0 mm, and 0 mm, for the concentrations of 100%, 75%, and 50%, respectively. We concluded that the majority of E. coli strains were able to harbor some virulence genes and resist many antibiotics. Our study also provided a robust evidence that the camel’s urine, particularly from the virgin camels has robust antimicrobial activity against multidrug-resistant E. coli strains.     

Standardization of factors that influence human urine metabolomics

In nutritional metabolomics a large inter- and intra-subject variability exists, and thus, it becomes important to limit the variance introduced by external factors. In a composite controlled study with full provision of all food for the standardized intervention, human urinary metabolite profiles were investigated for different factors, such as handling of urine collections, diet standardization, diet culture, cohabitation and gender. In study A, 8 healthy subjects (4 men; 4 women) collected 24-h urine, splitting each void into two specimens stored either at 4°C or at room temperature. In study B, 16 healthy subjects (7 men; 9 women) collected 24-h urine for three days while being on a standardized diet. Samples were analyzed by ¹H NMR and chemometrics. The NMR profiles indicated the presence of metabolites presumably originating from bacterial contamination in 3 out of 16 sample collections stored at room temperature. On the contrary, no changes in the NMR profiles due to contamination occurred in the 24-h urine samples stored at 4°C. The study also showed a trend towards a reduced inter- and intra-individual variation during 3 days of diet standardization. In study A, the urine metabolome showed a clear effect of diet culture and cohabitation, but these effects significantly attenuated after diet standardization (study B). Besides, gender-specific differences were found in both studies. Our results emphasize that best practice for any metabolomic study is a standardized, chilled sample collection procedure, and recommend that diet standardization is performed prior to dietary interventions in order to reduce intra- and inter-subject variability.