Fall in total cholesterol concentration over five years in association with changes in fatty acid composition of cooking oil in Mauritius: cross sectional survey.

OBJECTIVE: To determine the extent to which reducing the saturated fatty acid composition of a ubiquitously used cooking oil influenced changes in cholesterol concentration in the population during a five year intervention programme in Mauritius. DESIGN: Cross sectional surveys in 1987 and 1992 determined mean total cholesterol concentrations in the population. A random sample of respondents in the 1992 survey completed a nutrition questionnaire that included questions on diet in the previous 24 hours. SETTING: Mauritius. INTERVENTION: In 1987 the government of Mauritius changed the composition of the commonly used cooking oil from being mostly palm oil (high in saturated fatty acids) to being wholly soya bean oil (high in unsaturated fatty acids). SUBJECTS: 5080 and 5162 subjects in 1987 and 1992 cross sectional surveys. 2059 subjects aged 30-64 years were randomly selected from the respondents of the 1992 survey to take part in the nutrition survey. MAIN OUTCOME MEASURES: Fatty acid composition of phospholipids in pooled serum samples from men and women from the two surveys; measured and predicted change in serum cholesterol concentration. RESULTS: From 1987 to 1992 total cholesterol concentrations fell significantly by 0.79 mmol/l (P < 0.001) in men and 0.82 mmol/l (P < 0.001) in women. The estimated intake of saturated fatty acids decreased by 3.5% of energy intake in men and by 3.6% in women, and the intake of polyunsaturated fatty acids increased by 5.5% and 5.6% of energy intake, respectively. These changes were reflected in changes in the fatty acid composition of serum phospholipids, and according to Keys'' formula these changes explained much of the decrease in serum cholesterol concentrations (predicted decrease of 0.38 mmol/l in men and by 0.40 mmol/l in women). CONCLUSION: Dietary changes that entailed a reduction in the saturated fat content of a ubiquitous cooking oil explained most of the observed decrease in serum cholesterol concentration over five years in the population of Mauritius.     

Adipose Tissue Dysfunction and Altered Systemic Amino Acid Metabolism Are Associated with Non-Alcoholic Fatty Liver Disease

Background

Fatty liver is a major cause of obesity-related morbidity and mortality. The aim of this study was to identify early metabolic alterations associated with liver fat accumulation in 50- to 55-year-old men (n = 49) and women (n = 52) with and without NAFLD.

Methods

Hepatic fat content was measured using proton magnetic resonance spectroscopy (¹H MRS). Serum samples were analyzed using a nuclear magnetic resonance (NMR) metabolomics platform. Global gene expression profiles of adipose tissues and skeletal muscle were analyzed using Affymetrix microarrays and quantitative PCR. Muscle protein expression was analyzed by Western blot.

Results

Increased branched-chain amino acid (BCAA), aromatic amino acid (AAA) and orosomucoid were associated with liver fat accumulation already in its early stage, independent of sex, obesity or insulin resistance (p<0.05 for all). Significant down-regulation of BCAA catabolism and fatty acid and energy metabolism was observed in the adipose tissue of the NAFLD group (p<0.001for all), whereas no aberrant gene expression in the skeletal muscle was found. Reduced BCAA catabolic activity was inversely associated with serum BCAA and liver fat content (p<0.05 for all).

Conclusions

Liver fat accumulation, already in its early stage, is associated with increased serum branched-chain and aromatic amino acids. The observed associations of decreased BCAA catabolism activity, mitochondrial energy metabolism and serum BCAA concentration with liver fat content suggest that adipose tissue dysfunction may have a key role in the systemic nature of NAFLD pathogenesis.     

Amino acids inhibit Agrp gene expression via an mTOR-dependent mechanism

Metabolic fuels act on hypothalamic neurons to regulate feeding behavior and energy homeostasis, but the signaling mechanisms mediating these effects are not fully clear. Rats placed on a low-protein diet (10% of calories) exhibited increased food intake (P < 0.05) and hypothalamic Agouti-related protein (Agrp) gene expression (P = 0.002). Direct intracerebroventricular injection of either an amino acid mixture (RPMI 1640) or leucine alone (1 mug) suppressed 24-h food intake (P < 0.05), indicating that increasing amino acid concentrations within the brain is sufficient to suppress food intake. To define a cellular mechanism for these direct effects, GT1-7 hypothalamic cells were exposed to low amino acids for 16 h. Decreasing amino acid availability increased Agrp mRNA levels in GT1-7 cells (P < 0.01), and this effect was attenuated by replacement of the amino acid leucine (P < 0.05). Acute exposure to elevated amino acid concentrations increased ribosomal protein S6 kinase phosphorylation via a rapamycin-sensitive mechanism, suggesting that amino acids directly stimulated mammalian target of rapamycin (mTOR) signaling. To test whether mTOR signaling contributes to amino acid inhibition of Agrp gene expression, GT1-7 cells cultured in either low or high amino acids for 16 h and were also treated with rapamcyin (50 nM). Rapamycin treatment increased Agrp mRNA levels in cells exposed to high amino acids (P = 0.01). Taken together, these observations indicate that amino acids can act within the brain to inhibit food intake and that a direct, mTOR-dependent inhibition of Agrp gene expression may contribute to this effect.     

Influence of energy deficiency on the insulin-like growth factor I axis in a military training program.

The aim of this study was to determine wether continuous heavy physical activities as well as lack of food and sleep during military training (three weeks of conditioning followed by a five-day combat course) alter serum concentrations of IGF-I and/or its binding proteins, evaluating the relationship to metabolic changes. Before and after training, we measured serum levels of both total and free IGF-I, IGFBP-1 and IGFBP-3 as well as plasma levels of branched-chain amino acids (valine, leucine and isoleucine) and glucose from 26 cadets (21 +/- 2 yr). Total and free IGF-I levels were decreased after training from 228 +/- 12 to 160 +/- 7 ng/ml and from 0.80 +/- 0.08 to 0.52 +/- 0.06 ng/ml, p < 0.001 respectively) as well as IGFBP-3 (p < 0.001), while IGFBP-1 levels were increased (p < 0.001). BCAA levels were decreased from 245.4 +/- 7.5 to 215.9 +/- 5.1 micromol/l, p < 0.001, while those of glucose remained unchanged. There were correlations between changes in total IGF-I and IGFBP-3 (p < 0.05) and between free IGF-I and IGFBP-1 (p < 0.01). Several correlations appeared between changes in all the components of the IGF-I axis and branched-chain amino acids. We concluded that responses of the IGF-I system during an intense training could represent an adaptative response to the encountered energy deficiency, resulting a diversion of substrate from growth to acute metabolic needs.     

Sex, age, geographical location, smoking, and alcohol consumption influence serum selenium concentrations in the USA: third National Health and Nutrition Examination Survey, 1988-1994.

Selenium has been reported to reduce the risk for heart diseases and cancer. We examined the association of sex, age, geographical location, serum cotinine concentrations, a measure of smoking intensity, and alcohol consumption with serum selenium concentrations in the third National Health and Nutrition Examination Survey (NHANES III), 1988-1994. Study sample consisted of 14,619 apparently healthy individuals (male: 7,102; female: 7,517) aged 14 to >90 years. Sex, age, geographical location, serum cotinine concentrations, and alcohol consumption significantly influenced serum selenium concentrations (P < 0.05). The mean (+/- standard error) serum selenium concentration in men (124.5 +/- 0.20 ng/mL) was significantly higher than in women (122.0 +/- 0.20 ng/mL) (P < 0.0001). Men in the 31-50 y age group had the highest mean serum selenium concentration. In the same age group, women had the lowest mean serum selenium concentration. In both sexes, participants living in the Midwest and West had significantly higher serum selenium concentrations than those living in South and Northeast geographical locations. Serum cotinine was negatively associated with serum selenium concentrations in both men (beta = -0.0108; P < 0.0001 for trend) and women (beta = -0.0097; P < 0.0001 for trend). Alcohol consumption is positively associated with serum selenium in women (beta = 0.0462; P = 0.0044 for trend) but not in men (beta = 0.0015; P = 0.8496 for trend). Although, sex, age, geographical location, smoking, and alcohol intake influenced serum selenium concentrations, clinically low serum selenium concentrations are not common in the USA.     

Effects of increasing the intake of dietary β-glucans by exchanging wheat for barley on nutrient digestibility, nitrogen excretion, intestinal microflora, volatile fatty acid concentration and manure ammonia emissions in finishing pigs

An experiment (complete randomised design) was conducted to investigate the linear and quadratic effects of barley β-glucan inclusion level on total tract nutrient apparent digestibility, nitrogen excretion, intestinal microflora, volatile fatty acid (VFA) profile and manure ammonia emissions in pigs. Twenty-four boars (66 kg) were assigned to one of four treatments: (T1) 0 g/kg barley (control diet) (5.6 g/kg β-glucan), (T2) 222 g/kg barley (12.1 g/kg β-glucan), (T3) 444 g/kg barley (18.9 g/kg β-glucan) and (T4) 666 g/kg barley (25 g/kg β-glucan). Barley was substituted for wheat in the diet. The diets were formulated to contain similar concentrations of digestible energy and digestible lysine. There was a linear decrease (P < 0.001) in the total tract apparent digestibility of dry matter, organic matter, gross energy and neutral-detergent fibre with increasing β-glucan concentration. Faecal nitrogen excretion was affected by dietary β-glucan concentration (quadratic P < 0.05). There was a linear decrease in Enterobacteria concentrations (P < 0.05) with increasing dietary β-glucan concentration. Increasing dietary barley levels caused a linear decrease in colonic (P < 0.01) and caecal pH (P < 0.001). Total caecal VFA and propionic acid were affected by dietary β-glucan concentration (quadratic, P < 0.05). There was a linear decrease in the proportion of acetic acid (P < 0.001), isobutyric acid (P < 0.01) and isovaleric acid (P < 0.05) with increasing levels of dietary barley in both the caecum and colon. There was a linear increase in the proportion of propionic acid (P < 0.001) and butyric acid (P < 0.05) with increasing barley in the colon. In conclusion, high level of dietary β-glucan (25 g/kg) is required to reduce offensive odour forming branched-chain VFAs; however, diet digestibility is compromised at such levels.     

Visceral fat accumulation determines postprandial lipemic response,lipid peroxidation,DNA damage,and endothelial dysfunction in nonobese Korean men

Visceral fat has been associated with multiple cardiovascular disease (CVD) risk factors. The aim of this study was to identify anthropometrical measures most closely associated with some well-known CVD risk factors. Because most Asians at risk have normal body mass index (BMI) according to Western standards, we studied healthy nonobese Korean males (n = 102; age: 36.5 +/- 0.8 years, BMI: 23.8 +/- 0.2 kg/m2). Visceral fat area (VFA) at the fourth lumbar vertebra was associated with increased postprandial triglyceride (TG) response (r = 0.53, P < 0.001) and with plasma malondialdehyde (MDA) (r = 0.36, P < 0.01) and PGF2alpha (r = 0.24, P < 0.05). When matched for BMI and age, men with high VFA (HVFA) (>/=100 cm2; n = 27) had higher blood pressure (P < 0.01), increased consumption of cigarettes (P < 0.01), and lower ratio of energy expenditure to calorie intake (P < 0.01) as compared with low VFA men (<100 cm2; n = 27). Men with HVFA showed higher TG, glucose, and insulin responses following fat and oral glucose tolerance tests respectively higher plasma concentrations of MDA (P < 0.001), urinary PGF2alpha (P < 0.05), and lymphocytes deoxyribonucleic acid tail moments (P < 0.01). Conversely, HVFA was associated with lower testosterone, insulin-like growth factor-1, and brachial artery flow-mediated dilation (P < 0.001). In conclusion, our data indicate that visceral fat accumulation, even in nonobese men, is a major factor contributing to increased CVD risk.     

Fasting for 72 h increases intramyocellular lipid content in nondiabetic,physically fit men

The purpose of this study was to determine changes in intramyocellular lipid (IMCL) content in the vastus lateralis of nondiabetic, physically fit males over 72 h of fasting. Six men, mean age 35 yr (range 23-55 yr), body mass index 23.7 kg/m2 (21.2-27.4 kg/m2), undertook a water-only fast for 84 h. Vastus lateralis IMCL content was determined using proton magnetic resonance spectroscopy after 12 and 84 h of fasting. Venous blood was sampled at 12-h intervals throughout the fast. IMCL-(CH2)n/water and IMCL-(CH2)n/total creatine ratios increased from 0.00623 +/- 0.00065 to 0.0142 +/- 0.0015 (P = 0.002) and 6.82 +/- 0.87 to 14.96 +/- 1.73 (P = 0.001), respectively. Plasma free fatty acid (FFA), serum triglyceride, and whole blood 3-hydroxybutyrate concentrations increased (P < 0.001, <0.05, <0.03, respectively), whereas plasma glucose and serum insulin concentrations decreased (both P < 0.001) during fasting. In conclusion, 72-h water-only fasting produces a large increase in plasma FFA concentration, a drop in serum insulin concentration, and accumulation of IMCL in the vastus lateralis muscle of nondiabetic, physically fit men.     

Plasma norepinephrine is an independent predictor of vascular endothelial function with aging in healthy women

We tested the hypothesis that reductions in vascular endothelial function (endothelium-dependent dilation, EDD) with age are related to increases in sympathetic activity. Among 314 healthy men and women, age was inversely related to brachial artery flow-mediated dilation (FMD) (r = -0.30, P < 0.001), a measure of EDD, and positively related to plasma norepinephrine concentrations (PNE), a marker of sympathetic activity (r = 0.49, P < 0.001). Brachial FMD was inversely related to PNE in all subjects (r = -0.25, P < 0.001) and in men (n = 187, r = -0.17, P = 0.02) and women (n = 127, r = -0.37, P < 0.001) separately. After controlling for PNE (multiple regression analysis), brachial FMD remained significantly related to age in all subjects (r = -0.20, P < 0.001) and in men (r = -0.23, P < 0.01), but not women (r = -0.16, P = 0.06). Consistent with this, brachial FMD remained significantly related to PNE when controlling for age (r = -0.24, P < 0.01) and menopause status (r = -0.24, P < 0.01) in women. Indeed, PNE was the strongest independent correlate of brachial FMD in women after controlling for conventional cardiovascular disease risk factors (r = -0.22, P = 0.01). This relation persisted in a subset of women (n = 113) after further accounting for the effects of plasma oxidized low-density lipoprotein (P < 0.05), a circulating marker of oxidative stress. Endothelium-independent dilation was not related to age in either men or women (P > 0.05). These results provide the first evidence that EDD is inversely related to sympathetic activity, as assessed by PNE, among healthy adults varying in age. In particular, our findings suggest that sympathetic nervous system activity may be a key factor involved in the modulation of vascular endothelial function with aging in women.     

Feeding and arginine deficient diets differentially alter free amino acid concentrations of hindlimb muscle in young rats

Summary The objective of these experiments was to examine short- and long-term (7 d) effects of arginine-deficient diets on free amino acid concentrations in hindlimb muscle of rats. In rats fed the control diet containing arginine (+Arg), muscle alanine and methionine concentrations were higher 1 and 2h after feeding compared to food-deprived rats, whereas branched-chain amino acids, arginine and asparagine concentrations were lower postprandially. In Experiment 1, rats were fed an arginine-deficient (–Arg) diet with glutamate (+Glu) substituted for arginine; alanine (+Ala), ornithine (+Orn) or citrulline (+Cit) were substituted for arginine in Experiment 2. In Experiment 1, arginine concentrations decreased in blood but not in muscle. This contrasts with rats fed –Arg/+Ala or –Arg/+Orn diets which had muscle arginine concentrations less than half the concentrations in controls or in rats fed the –Arg/+Cit diet. Muscle essential amino acids in Experiment 2 did not differ by diet, but muscle branched-chain amino acids were elevated relative to controls in the rats fed –Arg/+Ala or –Arg/+Orn diets; however, rats fed the –Arg/+Cit diet had levels similar to the controls. Also, muscle branched-chain amino acids were correlated with glutamine concentrations in both blood and muscle. The measurements in the post-meal period suggest that muscle amino acid concentrations may more closely reflect dietary amino acid patterns than do blood amino concentrations.Abbreviations BCAA branched-chain amino acids - BCKADH branched-chain ketoacid dehydrogenase - EAA essential amino acids - LNAA large neutral amino acids - NEAA nonessential amino acids - PDV portal-drained viscera - SELSM standard error of least squares means - SSA 5-sulfosalicylic acid - TAA total amino acids Mention of a trade name, proprietary product or specific equipment does not constitute a guarantee by the US Department of Agriculture and does not imply its approval to the exclusion of other products that may be suitable.     

The effects of estrogen and progesterone on blood glutamate levels: evidence from changes of blood glutamate levels during the menstrual cycle in women

The gonadal steroids estrogen and progesterone have been shown to have neuroprotective properties against various neurodegenerative conditions. Excessive concentrations of glutamate have been found to exert neurotoxic properties. We hypothesize that estrogen and progesterone provide neuroprotection by the autoregulation of blood and brain glutamate levels. Venous blood samples (10 ml) were taken from 31 men and 45 women to determine blood glutamate, estrogen, progesterone, glucose, glutamate-pyruvate transaminase (GPT), and glutamate-oxaloacetate transaminase (GOT) levels, collected on Days 1, 7, 12, and 21 of the female participants' menstrual cycle. Blood glutamate concentrations were higher in men than in women at the start of menstruation (P < 0.05). Blood glutamate levels in women decreased significantly on Days 7 (P < 0.01), 12 (P < 0.001), and 21 (P < 0.001) in comparison with blood glutamate levels on Day 1. There was a significant decrease in blood glutamate levels on Days 12 (P < 0.001) and 21 (P < 0.001) in comparison with blood glutamate levels on Day 7. Furthermore, there was an increase in blood glutamate levels on Day 21 compared with Day 12 (P < 0.05). In women, there were elevated levels of estrogen on Days 7 (P < 0.05), 12, and 21 (P < 0.001), and elevated levels of progesterone on Days 12 and 21 (P < 0.001). There were no differences between men and women with respect to blood glucose concentrations. Concentrations of GOT (P < 0.05) and GPT (P < 0.001) were significantly higher in men than in women during the entire cycle. The results of this study demonstrate that blood glutamate levels are inversely correlated to levels of plasma estrogen and progesterone.     

Glutamine kinetics and protein turnover in end-stage renal disease

Alanine and glutamine constitute the two most important nitrogen carriers released from the muscle. We studied the intracellular amino acid transport kinetics and protein turnover in nine end-stage renal disease (ESRD) patients and eight controls by use of stable isotopes of phenylalanine, alanine, and glutamine. The amino acid transport kinetics and protein turnover were calculated with a three-pool model from the amino acid concentrations and enrichment in the artery, vein, and muscle compartments. Muscle protein breakdown was more than synthesis (nmol.min(-1).100 ml leg(-1)) during hemodialysis (HD) (169.8 +/- 20.0 vs. 125.9 +/- 21.8, P < 0.05) and in controls (126.9 +/- 6.9 vs. 98.4 +/- 7.5, P < 0.05), but synthesis and catabolism were comparable pre-HD (100.7 +/- 15.7 vs. 103.4 +/- 14.8). Whole body protein catabolism decreased by 15% during HD. The intracellular appearance of alanine (399.0 +/- 47.1 vs. 243.0 +/- 34.689) and glutamine (369.7 +/- 40.6 vs. 235.6 +/- 27.5) from muscle protein breakdown increased during dialysis (nmol.min(-1).100 ml leg(-1), P < 0.01). However, the de novo synthesis of alanine (3,468.9 +/- 572.2 vs. 3,140.5 +/- 467.7) and glutamine (1,751.4 +/- 82.6 vs. 1,782.2 +/- 86.4) did not change significantly intradialysis (nmol.min(-1).100 ml leg(-1)). Branched-chain amino acid catabolism (191.8 +/- 63.4 vs. -59.1 +/- 42.9) and nonprotein glutamate disposal (347.0 +/- 46.3 vs. 222.3 +/- 43.6) increased intradialysis compared with pre-HD (nmol.min(-1).100 ml leg(-1), P < 0.01). The mRNA levels of glutamine synthase (1.45 +/- 0.14 vs. 0.33 +/- 0.08, P < 0.001) and branched-chain keto acid dehydrogenase-E2 (3.86 +/- 0.48 vs. 2.14 +/- 0.27, P < 0.05) in the muscle increased during HD. Thus intracellular concentrations of alanine and glutamine are maintained during HD by augmented release of the amino acids from muscle protein catabolism. Although muscle protein breakdown increased intradialysis, the whole body protein catabolism decreased, suggesting central utilization of amino acids released from skeletal muscle.     

Serum bisphenol a concentrations showed gender differences, possibly linked to androgen levels

To investigate human exposure to bisphenol A (BPA), a widely used endocrine disruptor, we measured serum BPA concentrations and analyzed the interrelation of BPA with sex-related hormones. BPA was detected in all human sera by a novel enzyme-linked immunosorbent assay. Serum BPA concentrations were significantly higher in normal men (1.49 +/- 0.11 ng/ml; P < 0.01) and in women with polycystic ovary syndrome (1.04 +/- 0.10 ng/ml; P < 0.05) compared with normal women (0.64 +/- 0.10 ng/ml). There were significant positive correlations between serum BPA and total testosterone (r = 0.595, P < 0.001) and free testosterone (r = 0.609, P < 0.001) concentrations in all subjects and likewise between serum BPA and total testosterone (r = 0.559, P < 0.01) and free testosterone (r = 0.598, P < 0.001) concentrations in all female subjects, but not between serum BPA and other sex-related hormone concentrations in any group. These findings showed that there are gender differences in serum BPA concentrations, possibly due to differences in the androgen-related metabolism of BPA.     

Hyperglycemia after protein ingestion concurrent with injection of a GLP-1 receptor agonist in rats: a possible role for dietary peptides

Protein ingestion after injection of the glucagon-like peptide-1 receptor agonist Exendin-4 (Ex-4) causes hyperglycemia in rats. The objectives of this study were to determine the components of protein digestion responsible for this effect and to associate it with changes in the concentrations of other metabolites and hormones. Two experiments were conducted. In the first experiment, food-deprived rats were gavaged with intact whey (WP) or albumin protein, their hydrolysates, amino acid mixtures (1 g/2.5 ml), or water 5 min after injection of either PBS or Ex-4 (0.5 microg/rat). Tail vein blood was analyzed for glucose over 2 h. In the second experiment, food-deprived rats were gavaged with WP with or without Ex-4. Groups of conscious rats were killed by decapitation either before, or at selected times after gavage. Plasma concentrations of glucose, amino acids, free fatty acids (FFA), glycerol, insulin, glucagon, and leptin were measured. In experiment 1, blood glucose was higher when intact proteins and protein hydrolysates, but not amino acid mixtures, were given with than without Ex-4 (P < 0.05). In experiment 2, concentrations of glucose, FFA, and the ratio of tyrosine to branched-chain amino acid were higher (P < 0.01), but leptin and essential amino acid concentrations were lower (P < 0.05), and insulin, glucagon, and glycerol were similar when WP was given with or without Ex-4. We conclude that the hyperglycemia caused by the administration of Ex-4 concurrently with dietary protein arises from the action of peptides released during digestion and their interaction with Ex-4 in the regulation of glucose, fatty acid, and amino acid metabolism.     

The regulation of fatty acid and branched-chain amino acid oxidation in cancer cachectic rats: a proposed role for a cytokine, eicosanoid, and hormone trilogy

Some postulates of a hypothesis concerned with the deregulation of muscle turnover by the hypoketonemia of cachectic tumor-bearing rats were examined. Plasma concentrations of ketone bodies (D-(3)-hydroxybutyrate + acetoacetate) in rats bearing the Walker 256 carcinosarcoma were reduced by 45% (P less than 0.001) whereas the concentrations of triglyceride and free fatty acids were elevated by 223% (P less than 0.001) and 335% (P less than 0.001), respectively. Parallel with the changes in plasma, the livers of tumor-bearing animals showed decreased concentrations of KB by 35% (P less than 0.05) and increased concentrations of TG and FFA by 49% (NS) and 15% (NS), respectively. In comparison with values for the control liver (fed ad libitum), the perfused liver of animals bearing the Walker 256 tumor formed 42% (P less than 0.05) and 75% (P less than 0.05) less ketone bodies and CO2, respectively, from oleate, while TG formation was enhanced by 33% (P less than 0.001). There was two- to threefold (P less than 0.001) enhancement of [1-14C]leucine oxidation in vivo by the tumor-bearing animals. The activities of branched-chain amino acid aminotransferase and branched-chain keto acid dehydrogenase were elevated by 70% (P less than 0.001) and 560% (P less than 0.001) respectively in the gastrocnemius muscle of the tumor-bearing animals. The results of the investigation supported a second proposal of the hypothesis, namely, that cancer-induced cachexia resulted in the notable elevation in the concentration of arginine vasopressin that was accompanied by parallel increases in the plasma, urine, and muscle concentrations of prostaglandin E2. The proposals of the original hypothesis have been augmented to include roles for PGE2 and the cytokine cachectin/tumor necrosis factor which may engineer all of the events depicted in the original hypothesis.     

Essential Amino Acids in the Gluten-Free Diet and Serum in Relation to Depression in Patients with Celiac Disease

IntroductionCeliac disease (CD) is associated with an increased risk of major depressive disorder, possibly due to deficiencies in micronutrients in the gluten-free diet. We aimed to investigate whether essential amino acids (i.e., the precursors of serotonin, dopamine and other neurotransmitters) are depleted in the diet and serum of CD patients with major depressive disorder.MethodsIn a cross-sectional study we assessed dietary intake of amino acids and serum levels of amino acids, in 77 CD patients on a gluten-free diet and in 33 healthy controls. Major depressive disorder was assessed with structured interviews (using the Mini International Neuropsychiatric Interview Plus). Dietary intake was assessed using a 203-item food frequency questionnaire.ResultsParticipants had a mean age of 55 years and 74% were women. The intake of vegetable protein was significantly lower in CD patients than in healthy controls (mean difference of 7.8 g/d; 95% CI: 4.7–10.8), as were serum concentrations of tyrosine, phenylalanine and tryptophan (all p < 0.005). However, within the CD patient group, the presence of major depressive disorder (n = 42) was not associated with intake or serum levels of essential amino acids.ConclusionsPatients with CD on a long-term gluten-free diet, with good adherence, consume significantly less vegetable protein than controls, and their serum levels of several essential amino acids were also lower. Despite its potential adverse effect, intake and serum levels of essential amino acids were not related to major depression.     

Hydrogenation of polyunsaturated fatty acids by human colonic bacteria

Emulsions of the fatty acids linoleic (C18:2 n-6), alpha-linolenic (C18:3 n-3) and arachidonic acid (C20:4 n-6) were incubated for 4 h under anaerobic conditions with human faecal suspensions. Linoleic acid was significantly decreased (P < 0.001) and there was a significant rise (P < 0.05) in its hydrogenation product, stearic acid. Linolenic acid was also significantly decreased (P < 0.01), and significant increases in C18:3 cis-trans isomers (P < 0.01) and linoleic acid (P < 0.05) were seen. With each acid, there were non-significant increases in acids considered to be intermediates in biohydrogenation. The study provides evidence that bacteria from the human colon can hydrogenate C18 essential polyunsaturated fatty acids. However, with arachidonic acid there was no evidence of hydrogenation.     

Gender differences in the regulation of amino acid metabolism.

Exercising men, compared with women, have a greater increase in leucine oxidation but not lysine rate of appearance. The cause for this sexual dimorphism is unknown; however, an inhibition of beta-adrenoreceptor activity has previously been shown to mediate amino acid metabolism (Lamont LS, McCullough AJ, and Kalhan SC. Am J Physiol Endocrinol Metab 268: E910-E916, 1995; Lamont LS, Patel DG, and Kalhan SC. J Appl Physiol 67: 221-225, 1989). This study was a gender comparison of leucine and lysine kinetics during a beta-adrenoreceptor blockade (beta1,beta2-blockade) and a placebo control by using a double-blind crossover protocol. Subjects exercised at 50% of their trial-specific maximal O2 consumption (1 h) after 7 days of dietary control. During exercise with beta-blockade, men had an increased nonprotein respiratory exchange ratio (P < 0.001), whereas women had an increased circulation of free fatty acids (P < 0.001). The genders also displayed distinct differences in exercise amino acid kinetics. The men, but not the women, increased leucine oxidation (P < 0.005) and lysine rate of appearance (P < 0.009) when exercising during beta-adrenergic blockade. This study indicates that during beta-blockade, exercising men increase their need for amino acids (and carbohydrate) to fuel energy needs, whereas women increase their mobilization of fat, thereby requiring less alternative fuels such as carbohydrate and amino acids. Gender-specific fuel preferences during exercise are regulated by beta-adrenergic-receptor activity. Substrate availability during exercise appears to modulate the amino acid oxidation differences between genders.     

Operation Everest II: plasma lipid and hormonal responses during a simulated ascent of Mt. Everest

To examine the effect of hypobaric hypoxia on plasma lipid profiles, fasting blood samples were collected from six men (21-31 yr) at 760 Torr and periodically during a 40-day exposure to decreasing barometric pressure culminating in a final ambient pressure of 282 Torr. Preascent plasma total cholesterol concentration ([TC]) was decreased by 25% after the 40-day exposure (P less than 0.01). High-density lipoprotein concentrations ([HDL-C]) decreased 32% (P less than 0.001) with no alteration in the TC-to-HDL-C weight ratio. Plasma triglyceride concentration increased twofold during this period (P less than 0.01). There were no significant differences in fasting plasma free fatty acid concentrations or free fatty acid-to-albumin molar ratio throughout the study. Fasting plasma insulin levels were increased approximately twofold with no significant changes in glucagon concentration or the insulin-to-glucagon molar ratio. Plasma norepinephrine concentrations were increased threefold on reaching 282 Torr (P less than 0.01), with no significant changes in plasma epinephrine concentrations. Mean energy intake (kcal/day) decreased 42%, whereas mean body weights decreased by 8.9 +/- 0.8% (P less than 0.01) with exposure. Increased concentrations of insulin may lead to increased hepatic production of triglyceride-rich lipoproteins, thus eliciting metabolic changes independent of weight loss and dietary intake.     

Comparison of raloxifene and atorvastatin effects on serum lipids composition of healthy post-menopausal women

The aim of this study was to evaluate the effects of the selective oestrogen receptor modulator, raloxifene, and those of statin, atorvastatin, in reducing the cardiovascular risks associated with the post-menopausal status. A detailed study of serum lipid concentrations was performed in four groups of post-menopausal women receiving either placebo, raloxifene or atorvastatin alone or their combination for the period of three months. Group A (raloxifene) showed significant decrease in total cholesterol levels (P < 0.05) and an increase in phospholipids concentration (P < 0.05), followed by a marked reduction in low-density lipoprotein cholesterol (LDL-C) levels (P < 0.01) and ApoB amounts (P < 0.001). Additionally, ApoA-I concentration was significantly increased (P < 0.01). Group B (atorvastatin) presented decreased cholesterol (P < 0.05) and triglycerides levels (P < 0.01), followed by elevated high-density lipoprotein cholesterol (HDL-C) concentration (P < 0.05) and low LDL-C amounts (P < 0.001). ApoA-I was significantly increased (P < 0.001) whereas ApoB was reduced (P < 0.001). The combined treatment in Group C (raloxifene and atorvastatin) showed significant changes in the majority of serum lipids. In particular, total cholesterol was reduced (P < 0.001), as well as triglycerides (P < 0.001) levels. Phospholipids were raised (P < 0.01) whereas LDL-C was reduced (P < 0.001) as was ApoB (P < 0.001). Furthermore, ApoA-I was elevated (P < 0.001). A further attempt to evaluate each treatment group was performed and the significance of these results is discussed.