Effects of chronic stress and high-fat diet on metabolic and nutritional parameters in Wistar rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of chronic stress and high-fat diet on metabolic and nutritional parameters in Wistar rats

Objective: The aim of this study was assess the role of chronic stress on the metabolic and nutritional profile of rats exposed to a high-fat diet. Materials and methods: Thirty-day-old male Wistar rats (70-100 g) were distributed into four groups: normal-diet (NC), chronic stress (St), high-fat diet (HD), and chronic stress/high-fat diet (HD/St). Stress consisted at immobilization during 15 weeks, 5 times per week, 1h per day; and exposure to the high-fat diet lasted 15 weeks. Nutritional and metabolic parameters were assessed. The level of significance was 5%. Results: The HD group had final body weight, total fat, as well as insulin and leptin increased, and they were insulin resistant. The St and HD/St had arterial hypertension and increased levels of corticosterone. Stress blocked the effects of the high-fat diet. Conclusion: Chronic stress prevented the appearance of obesity. Our results help to clarify the mechanisms involved in metabolic and nutritional dysfunction, and contribute to clinical cases linked to stress and high-fat diet.

Natural abundance of stable isotopes (15N and 13C) and isotopic fractionation of sea bream muscle as markers of food and culture conditions and its relationship with metabolic and proteomic analyses

Els isòtops estables com a traçadors de la cadena alimentària, s'han utilitzat per caracteritzar la relació entre els consumidors i els seus aliments, ja que el fraccionament isotòpic implica una discriminació en contra de certs isòtops. Però les anàlisis d'isòtops estables (SIA), també es poden dur a terme en peixos cultivats amb dietes artificials, com la orada (Sparus aurata), la especie más cultivada en el Mediterráneo. Canvis en l'abundància natural d'isòtops estables (13C i 15N) en els teixits i les seves reserves poden reflectir els canvis en l'ús i reciclatge dels nutrients ja que els enzims catabòlics implicats en els processos de descarboxilació i desaminació mostren una preferència pels isòtops més lleugers. Per tant, aquestes anàlisis ens poden proporcionar informació útil sobre l'estat nutricional i metabòlic dels peixos. L'objectiu d'aquest projecte va ser determinar la capacitat dels isòtops estables per ser utilitzats com a marcadors potencials de la capacitat de creixement i condicions de cria de l'orada. En aquest sentit, les anàlisis d'isòtops estables s'han combinat amb altres metabòlics (activitats citocrom-c-oxidasa, COX, i citrat sintasa, CS) i els paràmetres de creixement (ARN/ADN). El conjunt de resultats obtinguts en els diferents estudis realitzats en aquest projecte demostra que el SIA, en combinació amb altres paràmetres metabòlics, pot servir com una eina eficaç per discriminar els peixos amb millor potencial de creixement, així com a marcador sensible de l'estat nutricional i d'engreix. D'altra banda, la combinació de l'anàlisi d'isòtops estables amb les eines emergents, com ara tècniques de proteòmica (2D-PAGE), ens proporciona nous coneixements sobre els canvis metabòlics que ocorren en els músculs dels peixos durant l‟increment del creixement muscular induït per l'exercici.

Training in flexible intensive insulin therapy improves quality of life, decreases the risk of hypoglycaemia and ameliorates poor metabolic control in patients with type 1 diabetes.

AIM: Intensified insulin therapy has evolved to be the standard treatment of type 1 diabetes. However, it has been reported to increase significantly the risk of hypoglycaemia. We studied the effect of structured group teaching courses in flexible insulin therapy (FIT) on psychological and metabolic parameters in patients with type 1 diabetes. METHODS: We prospectively followed 45 type 1 diabetic patients of our outpatient clinic participating in 5 consecutive FIT teaching courses at the University Hospital of Basel. These courses consist of 7 weekly ambulatory evening group sessions. Patients were studied before and 1, 6, and 18 months after the course. Main outcome measures were glycated haemoglobin (HbA1c), severe hypoglycaemic events, quality of life (DQoL), diabetes self-control (IPC-9) and diabetes knowledge (DWT). RESULTS: Quality of life, self-control and diabetes knowledge improved after the FIT courses (all p<0.001). The frequency of severe hypoglycaemic events decreased ten-fold from 0.33 episodes/6 months at baseline to 0.03 episodes/6 months after 18 months (p<0.05). Baseline HbA1c was 7.2+/-1.1% and decreased in the subgroup with HbA1c > or = 8% from 8.4% to 7.8% (p<0.05). CONCLUSIONS: In an unselected, but relatively well-controlled population of type 1 diabetes, a structured, but not very time consuming FIT teaching programme in the outpatient setting improves psychological well-being and metabolic parameters.

Differential effects of pro- and anti-inflammatory cytokines alone or in combinations on the metabolic profile of astrocytes.

We have previously reported that the pro-inflammatory cytokines tumor necrosis factor-α (TNFα) and interleukin-1β (IL-1β) induce profound modifications of the metabolic profile of astrocytes. The present study was undertaken to further characterize the effects of cytokines in astrocytes and to determine whether similar effects could also be observed in neurons. To do so, selected pro-inflammatory (IL-6 and interferon-γ, in addition to the above-mentioned TNFα and IL-1β) and anti-inflammatory cytokines (IL-4, IL-10, transforming growth factor-β1 and interferon-β) were applied to primary neuronal and astrocytic cultures, and key metabolic parameters were assessed. As a general pattern, we observed that pro-inflammatory cytokines increased glucose utilization in astrocytes while the anti-inflammatory cytokines IL-4 and IL-10 decreased astrocytic glucose utilization. In contrast, no significant change could be observed in neurons. When pairs of pro-inflammatory cytokines were co-applied in astrocytes, several additive or synergistic modifications could be observed. In contrast, IL-10 partially attenuated the effects of pro-inflammatory cytokines. Finally, the modifications of the astrocytic metabolism induced by TNFα + IL-1β and interferon-γ modulated neuronal susceptibility to an excitotoxic insult in neuron-astrocyte co-cultures. Together, these results suggest that pro- and anti-inflammatory cytokines differentially affect the metabolic profile of astrocytes, and that these changes have functional consequences for surrounding neurons.

Association of PCK1 with Body Mass Index and Other Metabolic Features in Patients With Psychotropic Treatments.

Weight gain is a major health problem among psychiatric populations. It implicates several receptors and hormones involved in energy balance and metabolism. Phosphoenolpyruvate carboxykinase 1 is a rate-controlling enzyme involved in gluconeogenesis, glyceroneogenesis and cataplerosis and has been related to obesity and diabetes phenotypes in animals and humans. The aim of this study was to investigate the association of phosphoenolpyruvate carboxykinase 1 polymorphisms with metabolic traits in psychiatric patients treated with psychotropic drugs inducing weight gain and in general population samples. One polymorphism (rs11552145G > A) significantly associated with body mass index in the psychiatric discovery sample (n = 478) was replicated in 2 other psychiatric samples (n1 = 168, n2 = 188), with AA-genotype carriers having lower body mass index as compared to G-allele carriers. Stronger associations were found among women younger than 45 years carrying AA-genotype as compared to G-allele carriers (-2.25 kg/m, n = 151, P = 0.009) and in the discovery sample (-2.20 kg/m, n = 423, P = 0.0004). In the discovery sample for which metabolic parameters were available, AA-genotype showed lower waist circumference (-6.86 cm, P = 0.008) and triglycerides levels (-5.58 mg/100 mL, P < 0.002) when compared to G-allele carriers. Finally, waist-to-hip ratio was associated with rs6070157 (proxy of rs11552145, r = 0.99) in a population-based sample (N = 123,865, P = 0.022). Our results suggest an association of rs11552145G > A polymorphism with metabolic-related traits, especially in psychiatric populations and in women younger than 45 years.

Association of PCK1 with Body Mass Index and Other Metabolic Features in Patients With Psychotropic Treatments.

Weight gain is a major health problem among psychiatric populations. It implicates several receptors and hormones involved in energy balance and metabolism. Phosphoenolpyruvate carboxykinase 1 is a rate-controlling enzyme involved in gluconeogenesis, glyceroneogenesis and cataplerosis and has been related to obesity and diabetes phenotypes in animals and humans. The aim of this study was to investigate the association of phosphoenolpyruvate carboxykinase 1 polymorphisms with metabolic traits in psychiatric patients treated with psychotropic drugs inducing weight gain and in general population samples. One polymorphism (rs11552145G > A) significantly associated with body mass index in the psychiatric discovery sample (n = 478) was replicated in 2 other psychiatric samples (n1 = 168, n2 = 188), with AA-genotype carriers having lower body mass index as compared to G-allele carriers. Stronger associations were found among women younger than 45 years carrying AA-genotype as compared to G-allele carriers (-2.25 kg/m, n = 151, P = 0.009) and in the discovery sample (-2.20 kg/m, n = 423, P = 0.0004). In the discovery sample for which metabolic parameters were available, AA-genotype showed lower waist circumference (-6.86 cm, P = 0.008) and triglycerides levels (-5.58 mg/100 mL, P < 0.002) when compared to G-allele carriers. Finally, waist-to-hip ratio was associated with rs6070157 (proxy of rs11552145, r = 0.99) in a population-based sample (N = 123,865, P = 0.022). Our results suggest an association of rs11552145G > A polymorphism with metabolic-related traits, especially in psychiatric populations and in women younger than 45 years.

Inflammatory and metabolic responses to high-fat meals with and without dairy products in men.

Postprandial inflammation is an important factor for human health since chronic low-grade inflammation is associated with chronic diseases. Dairy products have a weak but significant anti-inflammatory effect on postprandial inflammation. The objective of the present study was to compare the effect of a high-fat dairy meal (HFD meal), a high-fat non-dairy meal supplemented with milk (HFM meal) and a high-fat non-dairy control meal (HFC meal) on postprandial inflammatory and metabolic responses in healthy men. A cross-over study was conducted in nineteen male subjects. Blood samples were collected before and 1, 2, 4 and 6 h after consumption of the test meals. Plasma concentrations of insulin, glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, TAG and C-reactive protein (CRP) were measured at each time point. IL-6, TNF-α and endotoxin concentrations were assessed at baseline and endpoint (6 h). Time-dependent curves of these metabolic parameters were plotted, and the net incremental AUC were found to be significantly higher for TAG and lower for CRP after consumption of the HFM meal compared with the HFD meal; however, the HFM and HFD meals were not different from the HFC meal. Alterations in IL-6, TNF-α and endotoxin concentrations were not significantly different between the test meals. The results suggest that full-fat milk and dairy products (cheese and butter) have no significant impact on the inflammatory response to a high-fat meal.

Arterial hypertension and metabolic profile in patients with polycystic ovary syndrome

PURPOSE: To evaluate parameters related with arterial pressure and metabolic profile in women with polycystic ovary syndrome (POS). METHODS: This monocentric study at the University Hospital Endocrinology Section included 60 women aged 18-45 years, 42 being diagnosed with POS and acting as 18 controls. All women were subjected to transvaginal ultrasound and monitored for arterial pressure for 24 h in the ambulatory (MAP). Venous blood samples were taken between 07.00 and 09.00, after 12 h fasting. Basal (BG) and fasting glucose concentrations, total cholesterol and its fractions, triglycerides and insulin (to calculate the homeostatic assay insulin-resistance, HOMA-IR) were measured. Collected data were the mean arterial blood pressure (24-h awake/sleep cycle), arterial pressure nocturnal descensus, glycemia and fasting glucose for HOMA-IR, and lipid profile. The Student's t test was used to compare homogeneous variables; the Mann-Whitney test was used to compare non-homogeneous variables; the Pearson's correlation coefficient was used to search for correlation between the variables. The c² test was used for comparison of the absence of nocturnal descensus. Significance was taken as p<0.05. RESULTS: The mean age of the patients with POS was 27.4±5.5 (18-45 years, n=42) and the body mass index (BMI) was 30.2±6.5 kg/m² (18.3-54.9). In the Control Group, the mean age was 31.4±6.1 (18-45 years) and the BMI was 27.1±6.2 kg/m² (18.3-54.9, n=18). No difference in the metabolic parameters and insulin resistance was observed between the two groups. Comparison between these parameters and MAP showed that the only parameter with a correlation was the BMI, independent of the POS diagnosis. This was not seen in nocturnal descensus, which was uncorrelated with POS and any of the other studied parameters. CONCLUSION: POS women do not show higher arterial blood pressure, glycemia, HDL-col, TG, HOMA-IR and BMI compared to non-POS women. However, POS patients showed correlation between arterial pressure and BMI, suggesting that obesity is a primary factor involved in arterial pressure changes in these patients.

Exercise training prevents increased intraocular pressure and sympathetic vascular modulation in an experimental model of metabolic syndrome

The present study aimed to study the effects of exercise training (ET) performed by rats on a 10-week high-fructose diet on metabolic, hemodynamic, and autonomic changes, as well as intraocular pressure (IOP). Male Wistar rats receiving fructose overload in drinking water (100 g/L) were concomitantly trained on a treadmill for 10 weeks (FT group) or kept sedentary (F group), and a control group (C) was kept in normal laboratory conditions. The metabolic evaluation comprised the Lee index, glycemia, and insulin tolerance test (KITT). Arterial pressure (AP) was measured directly, and systolic AP variability was performed to determine peripheral autonomic modulation. ET attenuated impaired metabolic parameters, AP, IOP, and ocular perfusion pressure (OPP) induced by fructose overload (FT vs F). The increase in peripheral sympathetic modulation in F rats, demonstrated by systolic AP variance and low frequency (LF) band (F: 37±2, 6.6±0.3 vs C: 26±3, 3.6±0.5 mmHg2), was prevented by ET (FT: 29±3, 3.4±0.7 mmHg2). Positive correlations were found between the LF band and right IOP (r=0.57, P=0.01) and left IOP (r=0.64, P=0.003). Negative correlations were noted between KITT values and right IOP (r=-0.55, P=0.01) and left IOP (r=-0.62, P=0.005). ET in rats effectively prevented metabolic abnormalities and AP and IOP increases promoted by a high-fructose diet. In addition, ocular benefits triggered by exercise training were associated with peripheral autonomic improvement.

First lactation ovarian function in dairy heifers in relation to prepubertal metabolic profiles

The aim of this study was to determine whether any differences in the GH-IGF-I axis in juvenile calves were predictive of fertility problems as adult cows. Endogenous metabolic hormone profiles before and after feeding and the response to a GH-releasing factor (GRF) challenge were measured in prepubertal (6 month) dairy calves. These metabolic parameters were subsequently related to physical characteristics at puberty and to ovarian function during the first lactation. Milk progesterone analysis was used to categorize the animals into those with normal progesterone profiles following calving (n = 17) and those that developed delayed ovulation (DOV1, n = 9) or persistent corpus luteum (PCL1, n = 6) profiles. There were associations between prepubertal GH parameters, glucose and non-esterified fatty acid (NEFA) concentrations and the body condition score at which the animals attained puberty. The calves which subsequently developed DOV1 profiles as cows tended to have a higher GH pulse amplitude during fasting than normal profile animals, they did not show the anticipated decrease in circulating glucose concentrations following a post-prandial rise in insulin and they also had the lowest IGF-I concentrations. The calves that later developed PCL1 had a significantly larger GH pulse amplitude and pulse area than normal profile animals in the fed period and had the highest IGF-I concentrations. There were no differences in prepubertal insulin or NEFA concentrations or in the GH response to a GRF challenge between the different progesterone profile categories. Plasma IGF-I concentrations in prepubertal animals were positively correlated with their post-calving concentrations, whereas glucose concentrations had a negative correlation between these time-periods. These results suggested that the different juvenile endocrine profiles of the DOV1 cows may predispose them to a higher rate of tissue mobilization during lactation and a consequent reduction in fertility, while altered GH and IGF-I levels in PCL1 cows may later contribute to the maintenance of the persistent corpus luteum. Therefore metabolic differences in prepubertal calves were later reflected by altered reproductive function during the first lactation.

Metabolic and hematologic consequences of colectomy associated to hepatectomy in rats

To investigate the influence of partial colectomy associated with hepatectomy on the biodistribution of the 99mTc-phytate, on metabolic parameters, as well as labeling and morphology of red blood cells. METHODS: Wistar rats were distributed into three groups (each with six), nominated as colectomy, colectomy+hepatectomy and sham. In the 30th postoperative day all rats were injected with 99mTc-phytate 0.1mL i.v. (radioactivity 0.66 MBq). After 15 minutes, liver sample was harvested and weighed. Percentage radioactivity per gram of tissue (%ATI/g) was determined using an automatic gammacounter. Serum AST, ALT, alkaline phosphatase and red blood cells labeling were determined. RESULTS: The liver %ATI/g and red blood cells labeling were lower in colectomy and colectomy+hepatectomy rats than in sham rats (p <0.05), and no difference was detected comparing the colectomy and colectomy+hepatectomy groups. Red blood cells morphology did not differ among groups. Serum levels of AST, ALT and alkaline fosfatase were significantly higher in colectomy+hepatectomy than in colectomy rats (p<0.001). CONCLUSION: Hepatectomy associated with colectomy lowered the uptake of radiopharmaceutical in liver and in red blood cells in rats, coinciding with changes in liver enzymatic activity.

Factors affecting metabolic and electrolyte changes after reperfusion in liver transplantation

Background. The metabolic and electrolyte changes were evaluated after various durations of cold and warm ischemia times to correlate ASA status with hemodynamic changes that may affect the severity of the reperfusion syndrome.Patients and methods. Sixty-one patients who underwent liver transplantation (OLT) were monitored by arterial pH, PaO2, PaCO2, HCO3, BE, K+, Ca2+, Na+, GL, and serial Ht at three specific times: after the skin incision (baseline), 10 minutes before reperfusion (T-2), and 10 minutes after reperfusion (T-3). Changes in metabolic parameters were correlated with ASA status, hemodynamic changes, time of OLT, as well as cold and warm ischemia times.Results. The pH in ASA IV patients was significantly lower at T-1 and T-3, and PCO2 higher in ASA V at T-1. A significant correlation was observed between pH, PaCO2, HCO3 BE, Na+, Ca2+, and glucose with the phase of the procedure. The pH and HCO3 decreased significantly from T-1 and T-2, increasing during T-3. Ca2+ fell from T-1 to T-2 increasing in T-3. Mean glucose and sodium levels increase from T-1 to T-3. Mean BE dropped from T-1 to T-2 and increased at T-3 without a significant correlation between the metabolic parameters in any phase of the study and the cold or warm ischemia times. Patients with a high ASA status showed an increased risk for cardiovascular collapse after reperfusion.Conclusions. Patients with advanced ASA status are more prone to metabolic and acid-base disturbances during reperfusion, without any relation to the cold or warm ischemia times. High ASA status shows an increased risk for cardiovascular collapse after reperfusion.

The effect of timing of thermal conditioning during incubation on embryo physiological parameters and its relationship to thermotolerance in adult broiler chickens

Previously, we reported that thermal conditioning at 39degreesC on days 13-17 of incubation of broiler eggs enabled thermotolerance during post-hatch growth (J. Therm. Biol. 28 (2003) 133). Tolerance to a temperature of 30degreesC was accompanied by changes in thyroid hormones and metabolic parameters. In the current study, we determined the mechanism of epigenetic heat adaptation during embryonic age by measuring blood physiological parameters that may be associated with the ultimate effects of thermal conditioning. Hatching eggs from Ross breeders were subjected to heat treatment of 39degreesC at days 13, 14, 15, 16 and 17 of incubation for 2 h per day. Control eggs were incubated at 37.6degreesC. Samples of eggs were withdrawn on each day of thermal conditioning and at internal pipping (IP) to obtain blood samples from embryos. The remaining eggs were weighed at day 18 and transferred to hatchers. The timing of IP, external pipping (EP) and hatching were monitored every 2 h. At hatch, chicks were weighed and hatchability was determined. Blood samples were obtained from samples of day-old chicks. T3, T4, corticosterone, pCO(2), pO(2) levels were determined in the blood. Blood pH was measured and T3/T4 ratios were calculated. Heat conditioning significantly increased corticosterone and pO(2) levels and blood pH but depressed pCO(2) at day 14. These were followed by a significant depression of T4 level on day 15. Remarkably, at day 16, all these parameters were back to normal as in the control embryos. Hatching was delayed by thermal conditioning probably as a result of the depressed corticosterone levels at IP. Hatchability was also lower in the heat-treated group but 1-day old chick weights were comparable to those of the controls. The result suggests that epigenetic thermal conditioning involves changes in these physiological parameters and probably serve as a method for epigenetic temperature adaptation since the same mechanisms are employed for coping with heat during post-embryonic growth. It also suggests that days 14-15 may be the optimal and most sensitive timing for evoking this mechanism during embryonic development. The adverse effects of heat treatment observed in this study may have been due to the continued exposure to heat until day 17. Fine-tuning thermal conditioning to days 14-15 only may improve these production parameters. (C) 2003 Elsevier Ltd. All rights reserved.

Monosodium glutamate in standard and high-fiber diets: Metabolic syndrome and oxidative stress in rats

Objective: This study determined the effects of adding monosodium glutamate (MSG) to a standard diet and a fiber-enriched diet on glucose metabolism, lipid profile, and oxidative stress in rats. Methods: Male Wistar rats (65 ± 5 g, n = 8) were fed a standard diet (control), a standard diet supplemented with 100 g of MSG per kilogram of rat body weight, a diet rich in fiber, or a diet rich in fiber supplemented with 100 g of MSG per kilogram of body weight. After 45 d of treatment, sera were analyzed for concentrations of insulin, leptin, glucose, triacylglycerol, lipid hydroperoxide, and total antioxidant substances. A homeostasis model assessment index was estimated to characterize insulin resistance. Results: Voluntary food intake was higher and feed efficiency was lower in animals fed the standard diet supplemented with MSG than in those fed the control, fiber-enriched, or fiber- and MSG-enriched diet. The MSG group had metabolic dysfunction characterized by increased levels of glucose, triacylglycerol, insulin, leptin, and homeostasis model assessment index. The adverse effects of MSG were related to an imbalance between the oxidant and antioxidant systems. The MSG group had increased levels of lipid hydroperoxide and decreased levels of total antioxidant substances. Levels of triacylglycerol and lipid hydroperoxide were decreased in rats fed the fiber-enriched and fiber- and MSG-enriched diets, whereas levels of total antioxidant substances were increased in these animals. Conclusions: MSG added to a standard diet increased food intake. Overfeeding induced metabolic disorders associated with oxidative stress in the absence of obesity. The fiber-enriched diet prevented changes in glucose, insulin, leptin, and triacylglycerol levels that were seen in the MSG group. Because the deleterious effects of MSG, i.e., induced overfeeding, were not seen in the animals fed the fiber-enriched diets, it can be concluded that fiber supplementation is beneficial by discouraging overfeeding and improving oxidative stress that is induced by an MSG diet. © 2005 Elsevier Inc. All rights reserved.