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Biomedical subjects

Daniel Tomé

Publications and source records attributed to Daniel Tomé.

At least 19 recordsLinked to original sources
PubMed2006

Liver glyconeogenesis: a pathway to cope with postprandial amino acid excess in high-protein fed rats?

This paper provides molecular evidence for a liver glyconeogenic pathway, that is, a concomitant activation of hepatic gluconeogenesis and glycogenesis, which could participate in the mechanisms that cope with amino acid excess in high-protein (HP) fed rats. This evidence is based on the concomitant upregulation of phosphoenolpyruvate carboxykinase (PEPCK) gene expression, downregulation of glucose 6-phosphatase catalytic subunit (G6PC1) gene expression, an absence of glucose release from isolated hepatocytes and restored hepatic glycogen stores in the fed state in HP fed rats. These effects are mainly due to the ability of high physiological concentrations of portal blood amino acids to counteract glucagon-induced liver G6PC1 but not PEPCK gene expression. These results agree with the idea that the metabolic pathway involved in glycogen synthesis is dependent upon the pattern of nutrient availability. This nonoxidative glyconeogenic disposal pathway of gluconeogenic substrates copes with amino excess and participates in adjusting both amino acid and glucose homeostasis. In addition, the pattern of PEPCK and G6PC1 gene expression provides evidence that neither the kidney nor the small intestine participated in gluconeogenic glucose production under our experimental conditions. Moreover, the main glucose-6-phosphatase (G6Pase) isoform expressed in the small intestine is the ubiquitous isoform of G6Pase (G6PC3) rather than the G6PC1 isoform expressed in gluconeogenic organs.

Amino Acids↗
PubMed2006

Medium-term methionine supplementation increases plasma homocysteine but not ADMA and improves blood pressure control in rats fed a diet rich in protein and adequate in folate and choline.

BACKGROUND: Hyperhomocysteinemia (HHcy) is associated with cardiovascular risk, possibly because it increases asymmetric dimethyl-arginine (ADMA), but the general association remains unclear and may vary with nutritional and physiological conditions. AIM OF THE STUDY: We aimed to monitor the effect of methionine supplementation, and subsequent HHcy, on plasma ADMA and hemodynamics in the context of a diet rich in protein and adequate in folic acid and choline. METHODS: For 6 weeks, rats were fed a 29% protein diet supplemented (M) or not (C) with 8 g/kg L: -methionine. Blood pressure and plasma amino acids, including homocysteine and ADMA, were measured throughout the experiment and additional parameters, including in vivo hemodynamic response to acetylcholine, were measured at week 5-6. RESULTS: As compared to the C diet, the M diet induced a marked HHcy during the first 3 weeks, which lessened at week 5. In contrast, plasma ADMA stayed similar in the C and M diet. Paradoxically, M rats had lower mean and diastolic blood pressure values over the experiment, together with a lower left ventricular mass at week 6, when compared with C rats. No difference was observed between groups regarding vascular reactivity and plasma NOx at week 6. CONCLUSIONS: In a context of a diet rich in protein and adequate in methyl donors, rats exhibit a complex adaptation to the medium-term methionine supplementation, with improvement in blood pressure control despite marked HHcy. The lack of increase in plasma ADMA may account for the absence of detrimental effects of HHcy on hemodynamics.

Adaptation, Physiological↗
PubMed2006

A model for antipsychotic-induced obesity in the male rat.

INTRODUCTION: Weight gain is a common and severe side effect of antipsychotic drugs. A usual tool to study the side effects of psychotropic drugs is animal models. However, attempts to create an animal model of antipsychotic-induced weight gain were not successful so far. Female rodents are sensitive to the effects of antipsychotics, but not males. This does not match the human clinical situation. Antipsychotics have different pharmacokinetic properties in rats and humans, and rats and humans have different spontaneous diets. MATERIALS AND METHODS: In the present study, we tested the hypothesis that the insensitivity of male rats to the weight-promoting effects of antipsychotics could be related to the mode of administration of antipsychotics and to the animals' diet. Antipsychotics were mixed with the food, and rats were fed a diet resembling the human diet. Rats were treated with 0.01, 0.1, 0.5, and 2 mg/kg of olanzapine or with a control solution for 6 weeks. Their weight and food intake were recorded, and their body composition were analyzed. The effects on weight and food intake of olanzapine (1 mg/kg), haloperidol (1 mg/kg), and ziprasidone (10 mg/kg) were also compared in a 3-week treatment experiment. RESULTS: The results showed that 0.5 and 2 mg of olanzapine, but not lower doses, increase body weight and subcutaneous fat deposition. After the 3-week treatment, olanzapine-treated rats, but not haloperidol- or ziprasidone-treated rats, had significantly increased their weight. CONCLUSION: This study shows that a rat model of obesity induced by antipsychotics can be created under specific conditions of drug administration, diet, and dose.

Animals↗
PubMed2006

Conceptual, methodological and computational issues concerning the compartmental modeling of a complex biological system: Postprandial inter-organ metabolism of dietary nitrogen in humans.

A multi-compartmental model has been developed to describe dietary nitrogen (N) postprandial distribution and metabolism in humans. This paper details the entire process of model development, including the successive steps of its construction, parameter estimation and validation. The model was built using experimental data on dietary N kinetics in certain accessible pools of the intestine, blood and urine in healthy adults fed a [15N]-labeled protein meal. A 13-compartment, 21-parameter model was selected from candidate models of increasing order as being the minimum structure able to properly fit experimental data for all sampled compartments. Problems of theoretical identifiability and numerical identification of the model both constituted mathematical challenges that were difficult to solve because of the large number of unknown parameters and the few experimental data available. For this reason, new robust and reliable methods were applied, which enabled (i) a check that all model parameters could theoretically uniquely be determined and (ii) an estimation of their numerical values with satisfactory precision from the experimental data. Finally, model validation was completed by first verifying its a posteriori identifiability and then carrying out external validation.

Adult↗
PubMed2006

Long term treatment with olanzapine mixed with the food in male rats induces body fat deposition with no increase in body weight and no thermogenic alteration.

Body weight gain is a worrying side effect of many new antipsychotic drugs. The mechanisms by which antipsychotic drugs increase weight in humans are not known. Attempts to model the metabolic effects of antipsychotic drugs in the animal have not been successful. Female rats appear to be sensitive to the effects of antipsychotics, but male rats less, and this does not match the clinical situation in humans. In previous rodent studies, antipsychotics were always given by daily gavage or injections. Antipsychotics have different pharmacokinetics in rodents and humans, and in the present study, we tested the hypothesis that the insensitivity of male rats to the effects of antipsychotics could be related to their mode of administration. Thus, we administered antipsychotic drugs mixed with the food. Animals were treated during 6 weeks with haloperidol (1mg/kg), olanzapine (1mg/kg), ziprasidone (10mg/kg), or a control solution. Animals were allowed to self-select food among three macronutrients (carbohydrates, lipids and proteins). Food selection was measured throughout the study. At the end of the study, body composition was measured by dissection and weighing of the rat's main organs and tissues. Mitochondrial thermogenesis was measured in brown adipose tissue in olanzapine-treated animals. Circulating leptin, insulin, glucose, triglycerides, cholesterol, high-density lipoprotein (HDL) were also assayed at the end of the study. The results show that none of the antipsychotic treatments modified caloric intake, food selection or body weight. Olanzapine did not alter mitochondrial thermogenesis. However, haloperidol and olanzapine induced a significant increase in adiposity and circulating leptin. Ziprasidone produced a moderate fat accumulation. It is concluded that mixing antipsychotic treatments with the food provides a reliable animal model of antipsychotic-induced fat accumulation.

Adipose Tissue↗
PubMed2006

Heat markers and quality indexes of industrially heat-treated [15N] milk protein measured in rats.

To determine the bioavailability of industrially heat-treated milk proteins, male Wistar rats were given [15N]-labeled meals containing either nonheated-micellar casein (CAS), milk soluble protein isolate (MSPI), and microfiltered milk (MF)-or heated products-"high temperature short time" pasteurized (HTST), "higher temperature, shorter time" pasteurized (HHST), ultrahigh temperature-treated (UHT), and spray-dried (SPRAY) milks. The postprandial distribution of dietary nitrogen was measured in the splanchnic area and urea. Digestibility was around 96% except for SPRAY (94%) and MSPI (98%). Ingested nitrogen recovered in the splanchnic bed was 19.3% for SPRAY, 16.7% for MF, and around 14-15% for other products. Deamination of dietary nitrogen reached 21.2, 20.6, and 18.2% of ingested nitrogen for MSPI, SPRAY, and CAS, respectively, and around 14-16% for other products. In our model, only spray drying led to a significant increase of splanchnic extraction. Moreover, the biological value of purified protein fractions appeared to be lower than that seen in products containing total milk protein.

Animals↗
PubMed2006

Chlorogenic acid is poorly absorbed, independently of the food matrix: A Caco-2 cells and rat chronic absorption study.

According to epidemiologic studies, dietary phenolic antioxidants, such as chlorogenic acid (CQA), could prevent coronary heart diseases and some cancers. Coffee is the main source of CQA in the human diet. The aim of this study was to assess the effect of usual coffee consumption conditions, such as the addition of milk, on CQA bioavailability. Interactions between CQA and milk proteins were shown, using an ultrafiltration technique. These interactions proved to be slightly disrupted during an in vitro digestion process. CQA absorption and bioavailability were then studied in vitro using a Caco-2 cell model coupled with an in vitro digestion process, and in vivo, in a chronic supplementation study in which rats were fed daily coffee or coffee and milk for 3 weeks. Both experiments showed that CQA absorption under its native form is weak, but unmodified by the addition of milk proteins, and slightly reduced by the addition of Maillard reaction products. These data show that there are some interactions between coffee phenolics and milk proteins, but these have no significant effect on CQA bioavailability from coffee in the rat. CQA is poorly absorbed under its native form in the body, when ingested in a realistic food matrix.

Absorption↗
PubMed2006

Compared with casein or total milk protein, digestion of milk soluble proteins is too rapid to sustain the anabolic postprandial amino acid requirement.

BACKGROUND: The in vivo quality of milk protein fractions has seldom been studied in humans. OBJECTIVE: Our objective was to compare the postprandial utilization of dietary nitrogen from 3 [(15)N]-labeled milk products: micellar caseins (MC), milk soluble protein isolate (MSPI), and total milk protein (TMP). DESIGN: The macronutrient intakes of 23 healthy volunteers were standardized for 1 wk, after which time the subjects ingested a meal containing MC (n = 8), MSPI (n = 7), or TMP (n = 8). [(15)N] was measured for an 8-h period in plasma amino acids, proteins, and urea and in urinary urea. RESULTS: The transfer of dietary nitrogen to urea occurred earlier after MSPI ingestion than after MC and TMP ingestion, and concentrations remained high for 8 h, concomitantly with higher but transient hyperaminoacidemia and a higher incorporation of dietary nitrogen into plasma amino acids. In contrast, deamination, postprandial hyperaminoacidemia, and the incorporation of dietary nitrogen into plasma amino acids were lower in the MC and TMP groups. Finally, total postprandial deamination values were 18.5 +/- 2.9%, 21.1 +/- 2.8%, and 28.2 +/- 2.9% of ingested nitrogen in the TMP, MC, and MSPI groups, respectively. CONCLUSIONS: Our results confirm the major role of kinetics in dietary nitrogen postprandial utilization and highlight the paradox of MSPI, which, despite its high Protein Digestibility Corrected Amino Acid Score, ensures a rate of amino acid delivery that is too rapid to sustain the anabolic requirement during the postprandial period. Milk proteins had the best nutritional quality, which suggested a synergistic effect between soluble proteins and caseins.

Adult↗
PubMed2006

A high-protein, high-fat, carbohydrate-free diet reduces energy intake, hepatic lipogenesis, and adiposity in rats.

The aim of this work was to determine the effects in rats of ingesting 1 of 3 diets with normal or high protein concentrations and various carbohydrate:lipid ratios on weight gain, body composition, and the development and metabolism of white adipose tissue (WAT). For this purpose, male Wistar rats were fed for 20 or 42 d a high-carbohydrate, low-fat, normal-protein diet (76, 10, and 14% of energy as carbohydrate, lipid, and protein, respectively, carbohydrate:lipid ratio (C/L) = 7.6), a normal-carbohydrate, low-fat, high-protein diet (35, 10, and 55% of energy as carbohydrate, lipid, and protein respectively, C:L = 3.5), or a carbohydrate-free, high-fat, high-protein diet (45 and 55% of energy as fat and protein, respectively, C:L = 0). Growth, food intake, body composition, WAT cellularity, and several markers of lipogenesis including fatty acid synthase and lipoprotein lipase activities were measured in adipose tissue and liver. Lowering the C:L ratio reduced the development of WAT, weight gain, body fat mass, and adipocyte size, and in rats fed the carbohydrate-free diet (C:L = 0), the total number of adipocytes in subcutaneous WAT. These reductions in adipose tissue development with decreases in the C:L ratio of the diet seemed to be due primarily to reduced hepatic lipogenesis.

Adipose Tissue↗
PubMed2006

The reduced energy intake of rats fed a high-protein low-carbohydrate diet explains the lower fat deposition, but macronutrient substitution accounts for the improved glycemic control.

The metabolic effect of high-protein low-carbohydrate (HP) diets on body composition and glucose homeostasis remains incompletely understood. This study assesses the respective roles of the increased protein:carbohydrate ratio (P:C) and the resulting moderate decrease in energy intake in the metabolic effects of HP diets. Rats had free access to normal (NP; 14%) or high (HP; 53%) total milk protein isoenergetic diets, or were fed the NP diet but restricted to the energy intake of HP rats (NPr), which was 89.1 +/- 9.3% that of NP rats. After 8 wk, body weight was lower in HP and NPr rats than in NP rats. In HP rats, the lower body weight was associated with a lower adipose tissue mass and a reduced proportion of large adipocytes. HP rats also had an improved oral glucose tolerance and insulin sensitivity, as assessed by the homeostatic model assessment index, compared with NPr and NP rats, and these effects were related solely to the increased P:C. These data suggest that the reduced energy intake of rats fed a high-protein, low-carbohydrate diet explains the lower fat deposition but an increased P:C per se improves glucose homeostasis.

Animals↗
PubMed2006

Yeast proteins enhance satiety in rats.

This study was designed to characterize the suppressant effect of yeast protein and purified peptides on energy intake. For this purpose, 5 experiments were carried out using adult male Wistar rats. Rats that consumed ad libitum a standard yeast protein diet ate significantly less and were leaner over 21 d than rats that consumed ad libitum a standard milk protein diet (Expt. 1). Moreover, rats fed a high yeast protein load reduced their next meal and daily energy intake more than rats fed any other well-balanced, amino acid, high protein load (soy, total milk protein, or wheat gluten) and more than those fed a wheat starch diet (Expt. 2). Purified peptides from the yeast protein extract produced similar effects on subsequent energy intake (Expt. 3). Study of the behavioral satiety sequence showed that rats consuming P14-y or P55-y diets ad libitum did not acquire a conditioned food aversion (Expt. 4). Finally, a preliminary study of gastric emptying in rats fed yeast protein loads showed that yeast protein was emptied more rapidly through the pylorus than total milk protein during a meal, which may induce satiety (Expt. 5). Taken together, these experiments show that yeast proteins enhance satiety in rats more than other proteins.

Animals↗
PubMed2006

Regulation of physiological and pathological Th1 and Th2 responses by lactoferrin.

In recent years, Lf has gained increasing interest as a result of its protective effects against a variety of diseases. While iron binding and interactions with mammalian receptors and microbial components are the best described mechanisms of action, recent studies have provided evidence that Lf properties may be related to immunoregulatory effects on Th1/Th2 cell activities. In vitro and in vivo experiments show that Lf is able to stimulate the differentiation of T cells from their immature precursors through the induction of the CD4 antigen. Studies performed under nonpathogenic conditions have shown distinct results with regard to the ability of Lf to support the proliferation and differentiation of Th cells into the Th1 or the Th2 phenotype. In addition, Lf plays different roles in diseases by affecting the Th1/Th2 cytokine balance in a manner dependent on the host's immune status. Thus, Lf could cause a Th1 polarization in diseases in which the ability to control infection or tumor relies on a strong Th1 response. Lf may also reduce the Th1 component to limit excessive inflammatory responses. Finally, Lf may provide protection against Th1- or Th2-induced diseases, such as autoimmune or allergic diseases, through correction of the Th1/Th2 imbalance.

Administration, Oral↗
PubMed2005

Comparison of energy balance in two inbred strains of rats: Fischer F344 prone to obesity and Lou rats resistant to obesity.

This study aimed to compare energy balance, metabolic profiles and body composition between two inbred strains of rats (F344 and Lou) submitted to a self-selecting macronutrient. During the 3 weeks of experiment, the two strains did not differ significantly for their total energy intake; males: F344 = 5875.4 +/- 171.4 kJ, Lou = 5619.2 +/- 349.4 kJ; and females: F344 = 4058.8 +/- 118.7 kJ, Lou = 3864.4+/-166.4 kJ. However, F344 rats showed a higher weight gain, and percentage of total fat tissue, together with a lower percentage of carcass weight than Lou rats regardless of sex. The percentages of each macronutrient revealed a lower preference of protein for F344 males and the opposite in females for CHO. The thermogenic activity measured in interscapular brown adipose tissue was lower in Fischer than in Lou while the reverse was observed for leptinemia and insulinemia. These results indicate that the mechanism responsible for the regulation of body composition observed in Lou rats takes place very early in life and attest the interest in this strain for studying the features of resistance to obesity.

Adipose Tissue↗
PubMed2005

A tryptic hydrolysate from bovine milk alphaS1-casein improves sleep in rats subjected to chronic mild stress.

The putative effects of a tryptic bovine alphaS1-casein hydrolysate on stress-induced sleep disorders were investigated and their possible link with typical blood stress parameters such as plasma corticosterone concentrations and glycaemia was assessed. Rats were subjected to chronic stress in the form of environmental disturbances, while receiving an oral administration of the alphaS1-casein hydrolysate (CH). Chronic stress significantly reduced sleep duration in control rats during the first 2 days of the stress period, but stress-induced sleep disturbance was prevented in CH-treated rats. Indeed, CH administration allowed the maintenance of slow wave sleep (SWS) duration and even a slight increase in paradoxical sleep (PS) duration in treated rats. Results on plasma corticosterone concentrations and on glycemia values were inconclusive with respect to the implication of the HPA axis in this study. However, the protective effect of the alphaS1-casein hydrolysate on sleep during exposure to our chronic mild stress conditions may be mediated by modulation of the central adrenergic response.

Animals↗
PubMed2005

In vivo leptin infusion impairs insulin and leptin signalling in liver and hypothalamus.

Leptin resistance contributes to the pathogenesis of common obesity related metabolic diseases, including insulin resistance. However, the relationship between leptin and insulin resistance is not clearly established. Here, we show that induced hyperleptinemia by leptin infusion alters insulin signalling in rat liver. Leptin infusion clearly reduced the insulin or leptin dependent IRS-1/IRS-2 association to p85 regulatory subunit of PI 3-kinase. Leptin infusion also abolished STAT-3 phosphorylation in response to insulin or leptin and similar results were obtained for MAP-kinase phosphorylation. Hypothalamic leptin resistance was also induced by leptin infusion since leptin was unable to induce STAT-3 phosphorylation. These results provide evidence that induced hyperleptinemia can contribute to the onset of insulin resistance at least at the hepatic level.

Animals↗
PubMed2005

Effects of chronic neuroleptic treatments on nutrient selection, body weight, and body composition in the male rat under dietary self-selection.

New antipsychotic drugs often increase weight and produce metabolic disturbances in treated patients. However, the mechanisms by which neuroleptics induce these undesirable side effects in humans are not known. Studies have shown that antipsychotics can increase body weight in female but not in male rats. However, no studies investigated changes in macronutrient selection during chronic treatments with antipsychotics in male rats, and no studies investigated precisely body composition after such treatments. In the present work, we studied in male rats the effects of long-term administration of two neuroleptics: haloperidol, a classical neuroleptic which has a moderate effect on weight gain in humans, and olanzapine, an atypical neuroleptic which has a more important effect on weight gain. Treatments (both 1 mg/kg) were given orally for 6 weeks, and the animals were allowed to self-select food among carbohydrates, lipids and proteins. Food selection was measured throughout the study, and body composition was measured by dissection and weighing of the main organs and tissues. Circulating leptin, insulin and glucose were also assayed at the end of the study on blood collected at the time of carcass analysis. The results show that none of the neuroleptic treatments modified caloric intake, food selection, body weight, and body composition. Olanzapine produced a statistically non-significant increase in subcutaneous fat tissue. It is concluded that a 6-week olanzapine or haloperidol treatment in male rats under dietary macronutrient selection does not significantly affect energy regulation.

Adipose Tissue↗
PubMed2005

Cryptosporidium infection impairs growth and muscular protein synthesis in suckling rats.

This study aimed to explore the metabolic consequences of cryptosporidiosis in an acute experimental model both at the peak of infection and after parasite clearance. Four-day-old suckling rats were infected with 10(6) oocysts of Cryptosporidium parvum. At the peak of infection (day 8 PI), C. parvum resulted in a dramatic reduction both in nutrient intake (-50%) and body weight (16.3+/-5.2 vs 27.3+/-1.0 g, P<0.01) with a decrease in both lean body mass and adipose tissue. Muscular fractional and absolute synthesis rate were reduced (-15 and -55%, respectively). After parasite clearance (day 17 PI), body weight remained reduced in formerly infected animals (37.8+/-8.0 vs 47.8+/-4.2 g, P<0.01) whereas nutrient intake normalized and fractional synthesis rate slightly increased (+22%) compared to controls. Overall, our results show that the impact and consequences of cryptosporidiosis are far greater than generally appreciated, leading to major malnutrition in suckling rats.

Animals↗