Amino acid imbalance in the liquid-fed lamb.

Eleven Poll Dorset times Merino crossbred female lambs 4 weeks of age were trained to suck liquid diets from bottles. In three separate experiments liquid diets providing 14-2% (expt 1) 10-6% (expt 2) or 8-0% (expt 3) of gross energy as protein and amino acids were fed. Responses in voluntary intake, growth rate and changes in plasma amino acid concentrations were studied when complete or incomplete mixtures of amino acids were added to the liquid diet. These mixtures supplied either: (1) all amino acids in quantities to bring the total of protein plus amino acids to provide more than 20% of dietary gross energy, the amino acids being provided in proportions estimated to meet adequately the lamb's requirements ('complete'); or (2) as the same total amount of amino acids but with the amino acid supplement devoid of threonine ('low-threonine', expts 1 and 2) or isoleucine ('low isoleucine', expt 3). In experiment 1, there was no food intake or growth depression after feeding the amino acid mixture lacking threonine. In both experiments 2 and 3, voluntary food intake was depressed to about 50% of that observed in lambs fed the low protein diet, when the amino acid mixture devoid of threonine or of isoleucine, respectively, was fed. Addition of the missing amino acid to the low threonine and low isoleucine diets resulted in recovery of voluntary intake in experiments 2 and 3 respectively, but no significant improvement above that found after feeding the low protein (basal) diet. In experiments 1 and 2, after feeding the low threonine diet the threonine concentration in the blood plasma decreased markedly, while concentrations of total amino acids were elevated. Although there was no improvement in growth or food intake, the feeding of the diet containing the complete amino acid mixture resulted in an elevation of all essential amino acids including threonin. Similarly in experiment 3, plasma isoleucine concentration decreased in the lambs fed the isoleucine imbalanced diet. Results indicate that the suckled, preruminant lamb exhibits sensitivity to dietary amino acid imbalance, in a manner analogous to that found in simple-stomached animals. These results also clearly illustrate a depression in food intake associated with the deletion of a specific essential nutrient from the diet of the lamb.     

Threonine Entry into Rat Brain After Diet-Induced Changes in Plasma Amino Acids

Abstract: Passage of amino acids across the blood-brain barrier is modified by the amino acid composition of the blood. Because blood amino acid concentrations respond to changes in protein intake, we have examined associations among diet, plasma amino acid patterns, and the rate of entry of threonine into the brain. Rats were adapted for 8 h/ day for 7–10 days to diets containing 6, 18 , or 50% casein before receiving a single, independently varied, final meal of a diet containing 0, 6, 18 , or 50% casein. After 4–7 h, they were anesthetized and infused intravenously with [¹⁴C]threonine for 5 min before plasma and brain samples were taken for determination of radioactivity and amino acid content. Plasma and brain threonine concentrations decreased as protein content increased in the diets to which the rats had been adapted. Plasma threonine concentrations increased twofold, from 1.6 to 3.0 m M , when rats adapted to 6% casein meals received a single 50% casein meal rather than a nonprotein meal; a fivefold increase, from 0.13 to 0.69 m M , occurred when rats had been previously adapted to 50% casein meals. Increasing the protein content of the final meal did not increase brain threonine concentrations. Highest and lowest rates of threonine entry into the brain occurred, respectively, in rats adapted to 6 and 50% casein meals. Changes in plasma threonine concentrations and threonine flux into brain reflected protein content of both pretreatment and final meals.     

Naloxone's effect on meal microstructure of sucrose and cornstarch diets

The opioid receptor antagonist naloxone decreases consumption of high-sucrose diets but does not reduce cornstarch diet intake in energy-restricted rats. Sucrose-fed rats eat at a much higher rate, consuming more food than cornstarch-fed rats. We examined meal microstructure using an automated weighing system in food-restricted rats eating either a high-sucrose or high-cornstarch diet. Sucrose-fed rats exhibited a higher rate of eating during their first meal compared with cornstarch-fed rats (0.34 vs. 0.20 g/min, respectively). However, naloxone did not reduce eating rate in either group. Naloxone decreased the size of the first meal in both diet groups by shortening the length of the meal. Naloxone's anorectic effect was more potent in the sucrose-fed rats. These results indicate that naloxone's heightened anorectic effect on sucrose diet consumption is not "rate dependent." Naloxone's anorectic actions may be modulated by two conditions, the sensory properties of food and the energy state of the animal. Thus the elevated anorectic potency of naloxone in energy-restricted sucrose-fed rats may reflect actions on neural systems that mediate orosensory and/or postingestive signals.     

Ghrelin response to protein and carbohydrate meals in relation to food intake and glycerol levels in obese subjects

Obese subjects have lower basal and an attenuated decrease of postprandial plasma ghrelin following carbohydrate-rich meals, while the response to protein is unknown. Therefore, plasma ghrelin levels were examined after ingestion of satiating amounts of a protein- or carbohydrate-rich meal in relation to food and energy intake and hunger/satiety ratings in 30 obese subjects followed 240 min later by ad lib sandwiches. Food intake and hunger/satiety ratings were identical while energy intake was significantly greater after bread (861 +/- 62.7 vs. 441 +/- 50.4 kcal, p < 0.001). Second meal food and energy intake were not different. Ghrelin decreased after bread, but increased by 50 pg/ml (p < 0.001) after meat. The corresponding increase of insulin was 55 vs. 9 microU/ml (p < 0.001). Glycerol levels decreased significantly less after the protein meal compared to carbohydrates. After protein glycerol was significantly correlated to the rise of ghrelin but not insulin. These data demonstrate that, in obese subjects, protein has no different satiating effect than carbohydrate despite divergent ghrelin levels. Energy intake corresponds to energy density of the respective food items. Ghrelin response to both meals is qualitatively similar but quantitatively attenuated compared to normal weight subjects. The relationship between ghrelin and glycerol would support recent observations of a possible role of ghrelin in fat metabolism.     

Effects of glucose supplementation on gastric emptying, blood glucose homeostasis, and appetite in the elderly

The aims of this study were to evaluate the effects of dietary glucose supplementation on gastric emptying (GE) of both glucose and fat, postprandial blood glucose homeostasis, and appetite in eight older subjects (4 males, 4 females, aged 65--84 yr). GE of a drink (15 ml olive oil and 33 g glucose dissolved in 185 ml water), blood glucose, insulin, gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), and appetite (diet diaries, visual analog scales, and food intake at a buffet meal consumed after the GE study) were evaluated twice, after 10 days on a standard or a glucose-supplemented diet (70 g glucose 3 times a day). Glucose supplementation accelerated GE of glucose (P < 0.05), but not oil; there was a trend for an increase in GIP (at 15 min, P = 0.06), no change in GLP-1, an earlier insulin peak (P < 0.01), and a subsequent reduction in blood glucose (at 75 min, P < 0.01). Glucose supplementation had no effect on food intake during each diet so that energy intake was greater (P < 0.001) during the glucose-supplemented diet. Appetite ratings and energy intake at the buffet meal were not different. We conclude that, in older subjects, glucose supplementation 1) accelerates GE of glucose, but not fat; 2) modifies postprandial blood glucose homeostasis; and 3) increases energy intake.     

High-level medium-chain triglyceride feeding and energy expenditure in normal-weight women

The objective of this study was to assess how short-term feeding of high levels of dietary medium-chain triglyceride (MCT) affect energy expenditure and postprandial substrate oxidation rates in normal-weight, premenopausal women. Eight healthy women were fed both a MCT-rich and an isocaloric long-chain triglyceride (LCT)-rich diet for two 1-week periods separated by a minimum of 21 days. The energy intake in each diet was 45% carbohydrates, 40% fat, and 15% protein. The 2 diets had either 60.81% or 1.11% of total fat energy from MCT with the remaining fat energy intake from LCT. On days 1 and 7 of each diet, resting metabolic rate and postprandial energy expenditure (EE) were measured by indirect calorimetry with a ventilated hood. Results indicated on days 1 and 7, there were no significant differences between diets for resting metabolic rate or mean postprandial EE. On both days 1 and 7, fat oxidation for the MCT-rich diet was significantly greater (0.0001 相似文献   

Glycomacropeptide, a low-phenylalanine protein isolated from cheese whey, supports growth and attenuates metabolic stress in the murine model of phenylketonuria

Phenylketonuria (PKU) is caused by a mutation in the phenylalanine (phe) hydroxylase gene and requires a low-phe diet plus amino acid (AA) formula to prevent cognitive impairment. Glycomacropeptide (GMP) contains minimal phe and provides a palatable alternative to AA formula. Our objective was to compare growth, body composition, and energy balance in Pah(enu2) (PKU) and wild-type mice fed low-phe GMP, low-phe AA, or high-phe casein diets from 3-23 wk of age. The 2 × 2 × 3 design included main effects of genotype, sex, and diet. Fat and lean mass were assessed by dual-energy X-ray absorptiometry, and acute energy balance was assessed by indirect calorimetry. PKU mice showed growth and lean mass similar to wild-type littermates fed the GMP or AA diets; however, they exhibited a 3-15% increase in energy expenditure, as reflected in oxygen consumption, and a 3-30% increase in food intake. The GMP diet significantly reduced energy expenditure, food intake, and plasma phe concentration in PKU mice compared with the casein diet. The high-phe casein diet or the low-phe AA diet induced metabolic stress in PKU mice, as reflected in increased energy expenditure and intake of food and water, increased renal and spleen mass, and elevated plasma cytokine concentrations consistent with systemic inflammation. The low-phe GMP diet significantly attenuated these adverse effects. Moreover, total fat mass, %body fat, and the respiratory exchange ratio (CO(2) produced/O(2) consumed) were significantly lower in PKU mice fed GMP compared with AA diets. In summary, GMP provides a physiological source of low-phe dietary protein that promotes growth and attenuates the metabolic stress induced by a high-phe casein or low-phe AA diet in PKU mice.     

Postprandial variations of plasma inflammatory markers in abdominally obese men

Objective: Abdominal obesity is associated with a fasting proinflammatory condition. However, not much is known of the potential variations in circulating inflammatory markers after food intake. The purpose of the present study was to examine postprandial changes in plasma tumor necrosis factor (TNF)‐α, interleukin (IL)‐6, and C‐reactive protein (CRP) concentrations in men and their potential associations with fat distribution and metabolic profile variables. Research Methods and Procedures: Thirty‐eight men were given a high‐fat meal in the morning after an overnight fast, and TNF‐α, IL‐6, and CRP levels were measured in plasma at 0, 4, and 8 hours after the meal. Physical and metabolic profiles were also assessed for each participant. Results: We observed a substantial increase in circulating IL‐6 levels (p < 0.0001) after the meal. Although postprandial variations in circulating TNF‐α levels across time failed to reach statistical significance (p = 0.02), we noted a significant decrease in plasma TNF‐α concentrations 4 hours (?10%, p < 0.001 vs. 0 hours) after food intake. Plasma CRP levels were not affected by the fat load. We also noted that insulin‐sensitive individuals displayed a less pronounced inflammatory response after food intake than insulin‐resistant subjects. Discussion: Results of the present study show that consumption of a high‐fat meal leads to an increase in plasma IL‐6 concentrations and transient decrease in circulating TNF‐α levels in overweight men. Our results suggest a possible role of insulin resistance in the modulation of the postprandial inflammatory response, which could, in turn, contribute to worsen the state of insulin resistance.     

Nutritional assessment of somatolactin function in gilthead sea bream (Sparus aurata): concurrent changes in somatotropic axis and pancreatic hormones

The role of somatolactin (SL) in the regulation of energy homeostasis in gilthead sea bream (Sparus aurata) has been analysed. First, a down-regulation of plasma SL levels in response to gross shifts in dietary amino acid profile and the graded replacement of fish meal by plant protein sources (50%, 75% and 100%) has been observed. Thus, the impaired growth performance with changes in dietary amino acid profile and dietary protein source was accompanied by a decrease in plasma SL levels, which also decreased over the course of the post-prandial period irrespective of dietary nitrogen source. Secondly, we examined the effect of SL and growth hormone (GH) administration on voluntary feed intake. A single intraperitoneal injection of recombinant gilthead sea bream SL (0.1 microg/g fish) evoked a short-term inhibition of feed intake, whereas the same dose of GH exerted a marked enhancement of feed intake that still persisted 1 week later. Further, we addressed the effect of arginine (Arg) injection upon SL and related metabolic hormones (GH, insulin-like growth factor-I (IGF-I), insulin and glucagon) in fish fed diets with different nitrogen sources. A consistent effect of Arg injection (6.6 micromol/g fish) on plasma GH and IGF-I levels was not found regardless of dietary treatment. In contrast, the insulinotropic effect of Arg was found irrespective of dietary treatment, although the up-regulation of plasma glucagon and glucose levels was more persistent in fish fed a fish meal based diet (diet FM) than in those fed a plant protein diet with a 75% replacement (diet PP75). In the same way, a persistent and two-fold increase in plasma SL levels was observed in fish fed diet FM, whereas no effect was found in fish fed diet PP75. Taken together, these findings provide additional evidence for a role of SL as a marker of energy status, which may be perceived by fish as a daily and seasonal signal of abundant energy at a precise calendar time.     

Effect of moderate physical activity on plasma leptin concentration in humans

In subjects who maintain a constant body mass, the increased energy expenditure induced by exercise must be compensated by a similar increase in energy intake. Since leptin has been shown to decrease food intake in animals, it can be expected that physical exercise would increase energy intake by lowering plasma leptin concentrations. This effect may be secondary either to exercise-induced negative energy balance or to other effects of exercise. To delineate the effects of moderate physical activity on plasma leptin concentrations, 11 healthy lean subjects (4 men, 7 women) were studied on three occasions over 3 days; in study 1 they consumed an isoenergetic diet (1.3 times resting energy expenditure) over 3 days with no physical activity; in study 2 the subjects received the same diet as in study 1, but they exercised twice daily during the 3 days (cycling at 60 W for 30 min); in study 3 the subjects exercised twice daily during the 3 days, and their energy intake was increased by 18% to cover the extra energy expenditure induced by the physical activity. Fasting plasma leptin concentration (measured on the morning of day 4) was unaltered by exercise [8.64 (SEM 2.22) 7.17 (SEM 1.66), 7.33 (SEM 1.72) 1 microg x l(-1) in studies 1, 2 and 3, respectively]. It was concluded that a moderate physical activity performed over a 3-day period does not alter plasma leptin concentrations, even when energy balance is slightly negative. This argues against a direct effect of physical exercise on plasma leptin concentrations, when body composition is unaltered.     

The intestinal peptide transporter PEPT1 is involved in food intake regulation in mice fed a high-protein diet

High-protein diets are effective in achieving weight loss which is mainly explained by increased satiety and thermogenic effects. Recent studies suggest that the effects of protein-rich diets on satiety could be mediated by amino acids like leucine or arginine. Although high-protein diets require increased intestinal amino acid absorption, amino acid and peptide absorption has not yet been considered to contribute to satiety effects. We here demonstrate a novel finding that links intestinal peptide transport processes to food intake, but only when a protein-rich diet is provided. When mice lacking the intestinal peptide transporter PEPT1 were fed diets containing 8 or 21 energy% of protein, no differences in food intake and weight gain were observed. However, upon feeding a high-protein (45 energy%) diet, Pept1(-/-) mice reduced food intake much more pronounced than control animals. Although there was a regain in food consumption after a few days, no weight gain was observed which was associated with a reduced intestinal energy assimilation and increased fecal energy losses. Pept1(-/-) mice on high-protein diet displayed markedly reduced plasma leptin levels during the period of very low food intake, suggesting a failure of leptin signaling to increase energy intake. This together with an almost two-fold elevated plasma arginine level in Pept1(-/-) but not wildtype mice, suggests that a cross-talk of arginine with leptin signaling in brain, as described previously, could cause these striking effects on food intake.     

Postnatal deficiency of essential fatty acids in mice results in resistance to diet-induced obesity and low plasma insulin during adulthood

Our objective was to investigate the long-term metabolic effects of postnatal essential fatty acid deficiency (EFAD). Mouse dams were fed an EFAD diet or an isoenergetic control diet 4 days before delivery and throughout lactation. The pups were weaned to standard diet (STD) and were later subdivided into two groups: receiving high fat diet (HFD) or STD. Body composition, energy expenditure, food intake and leptin levels were analyzed in adult offspring. Blood glucose and plasma insulin concentrations were measured before and during a glucose tolerance test. EFAD offspring fed STD were leaner with lower plasma leptin and insulin concentrations compared to controls. EFAD offspring fed HFD were resistant to diet-induced obesity, had higher energy expenditure and lower levels of plasma leptin and insulin compared to controls. These results indicate that the fatty acid composition during lactation is important for body composition and glucose tolerance in the adult offspring.     

Low-dose ghrelin infusion--evidence against a hormonal role in food intake

Ghrelin is the only peripheral orexigenic peptide of gastrointestinal origin. Its preprandial increase is supposed to initiate food intake. This assumption is based on studies with intravenously infused ghrelin in rather high doses and the correlation between ghrelin levels and hunger sensations. As yet it is unclear whether or not low dose ghrelin resulting in physiological and moderately supraphysiological plasma levels has an effect on hunger sensations, the wish for food intake and / or the quantity of the meal consumed. We examined 20 normal-weight males (age 25±1.7 years, BMI 24±0.5 kg/m(2)) in a prospective double-blind randomized fashion. On two different days they obtained a ghrelin infusion 1 ng/kg/min or intravenous saline starting one hour after a standardized meal. Hunger and satiety ratings were documented by visual analogue scales. A second meal was served on demand and consumed until feeling satiated. Time point of the second meal as well as ingested calories were registered. Prior to the start of i.v. ghrelin the postprandial decrease of active plasma ghrelin by 30 pg/ml was comparable. In the controls the postprandial reduction was significant until 210 min compared to basal. With i.v. ghrelin basal levels were reached within 10 min. The maximal rise was twice basal. No effect was observed on hunger and satiety ratings. The time period between the meals and the food quantity of the second meal were similar. During ghrelin infusion glucose and growth hormone but not insulin and cortisol levels were significantly higher after the second meal compared to saline. The present data demonstrate for the first time the effect of a low dose ghrelin infusion on food intake. Neither physiological nor moderably supraphysiological ghrelin levels were associated with any change of the various food intake parameters determined. These data do not favour a hormonal role of peripheral ghrelin in the regulation of food intake.     

Variables Influencing the Effect of a Meal on Brain Tryptophan

Previous work from our laboratory points to plasma free tryptophan being a useful predictor of brain tryptophan concentration in many circumstances. Other work, in particular various studies on the acute effects of food intake, has emphasized the roles of plasma total tryptophan and of plasma large neutral amino acids that compete with tryptophan for transport to the brain. We have now studied associations between the above variables under different dietary conditions. Rats were allowed to feed for restricted periods during a 12-h light-12-h dark cycle. In the first study, rats were given access to a carbohydrate diet for 2 h midway through the light cycle and following an 18-h fast. The resultant rise of brain tryptophan was explicable largely by the associated fall in large neutral amino acids. In a second study, rats were adapted to a regimen whereby they were allowed access to the standard laboratory diet for 4 h during the dark cycle for 3 weeks. A postprandial decrease in brain tryptophan was associated with a fall in free tryptophan and of its ratio to competing amino acids. The brain change could be attributed neither to changes in plasma total tryptophan (which increased) nor to changes of its ratio to the competers (which remained unchanged). Results as a whole are thus consistent with changes of plasma free tryptophan and large neutral amino acid concentrations affecting brain tryptophan concentration under different dietary circumstances. It is suggested that these influences serve to maintain brain tryptophan when dietary supplies are defective.     

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.     

Inter-organ relationships between glucose, lactate and amino acids in rats fed on high-carbohydrate or high-protein diets

1. Inter-organ relationships between glucose, lactate and amino acids were studied by determination of plasma concentrations in different blood vessels of anaesthetized rats fed on either a high-carbohydrate diet [13% (w/w) casein, 79% (w/w) starch] or a high-protein diet [50% (w/w) casein, 42% (w/w) starch]. The period of food intake was limited (09:00-17:00h), and blood was collected 4h after the start of this period (13:00h). 2. Glucose absorption was considerable only in rats fed on a high-carbohydrate diet. Portal-vein-artery differences in plasma lactate concentration were higher in rats fed on this diet, but not proportional to glucose absorption. Aspartate, glutamate and glutamine were apparently converted into alanine, but when dietary protein intake was high, a net absorption of glutamine occurred. 3. The liver removed glucose from the blood in rats fed on a high-carbohydrate diet, but glucose was released into the blood in rats fed on the high-protein diet, probably as a result of gluconeogenesis. Lactate uptake was very low when amino acid availability was high. 4. In rats on a high-protein diet, increased uptake of amino acids, except for ornithine, was associated with a rise in portal-vein plasma concentrations, and in many cases with a decrease in hepatic concentrations. 5. Hepatic concentrations of pyruvate and 2-oxo-glutarate decreased without a concomitant change in the concentrations of lactate and malate in rats fed on the high-protein diet, in spite of an increased supply of pyruvate precursors (e.g. alanine, serine, glycine), suggesting increased pyruvate transport into mitochondria. 6. High postprandial concentrations of plasma glucose and lactate resulted in high uptakes of these metabolites in peripheral tissues of rats on both diets. Glutamine was released peripherally in both cases, whereas alanine was taken up in rats fed on a high-carbohydrate diet, but released when the amino acid supply increased. 7. It is concluded that: the small intestine is the main site of lactate production, and the peripheral tissues are the main site for lactate utilization; during increased ureogenesis in fed rats, lactate is poorly utilized by the liver; the gut is the main site of alanine production in rats fed on a high-carbohydrate diet and the liver utilizes most of the alanine introduced into the portal-vein plasma in both cases.     

Postprandial plasma lipidome responses to a high-fat meal among healthy women

Postprandial lipemia consists of changes in concentrations and composition of plasma lipids after food intake, commonly presented as increased levels of triglyceride-rich lipoproteins. Postprandial hypertriglyceridemia may also affect high-density lipoprotein (HDL) structure and function, resulting in a net decrease in HDL concentrations. Elevated triglycerides (TG) and reduced HDL levels have been positively associated with risk of cardiovascular diseases development. Here, we investigated the plasma lipidome composition of 12 clinically healthy, nonobese and young women in response to an acute high-caloric (1135 kcal) and high-fat (64 g) breakfast meal. For this purpose, we employed a detailed untargeted mass spectrometry-based lipidomic approach and data was obtained at four sampling points: fasting and 1, 3 and 5 h postprandial. Analysis of variance revealed 73 significantly altered lipid species between all sampling points. Nonetheless, two divergent subgroups have emerged at 5 h postprandial as a function of differential plasma lipidome responses, and were thereby designated slow and fast TG metabolizers. Late responses by slow TG metabolizers were associated with increased concentrations of several species of TG and phosphatidylinositol (PI). Lipidomic analysis of lipoprotein fractions at 5 h postprandial revealed higher TG and PI concentrations in HDL from slow relative to fast TG metabolizers, but not in apoB-containing fraction. These data indicate that modulations in HDL lipidome during prolonged postprandial lipemia may potentially impact HDL functions. A comprehensive characterization of plasma lipidome responses to acute metabolic challenges may contribute to a better understanding of diet/lifestyle regulation in the metabolism of lipid and glucose.     

Metabolic and hormonal effects of test meals with various protein contents in pigs

The postprandial release of immunoreactive insulin, glucagon, gastrin, somatostatin, pancreatic polypeptide (PP), and gastric inhibitory polypeptide (GIP) was studied in parallel with the absorption of sugars and amino acids in conscious pigs. Six pigs fitted with permanent catheters in the portal vein and arterial blood system as well as within an electromagnetic flow probe around the portal vein received successively at 3-day intervals, three meals of 800 g each containing 0, 14, or 28% protein (semisynthetic diets based on fish protein). Blood samples were collected and portal blood flow was recorded during a postprandial period of 8 h. For the same level of feed intake, an increase in the dietary protein concentration led to a higher alpha-amino nitrogen absorption and to a lower appearance of reducing sugars in the portal vein; in addition, the carbohydrate absorption efficiency (amounts absorbed as a percentage of amounts ingested) was reduced, showing the competition between the absorption of amino acids and glucose. The largest absorption occurred during the first 4 h after the meal, but neither the digestion of proteins nor that of carbohydrates were finished 8 h after the meal since portoarterial differences could still be observed. All test meals induced a rise of portal and peripheral concentrations of insulin, gastrin, somatostatin, and PP, and of the systemic level of GIP. Glucagon increased after the 28% protein meal only. The rise of plasma insulin paralleled that of blood glucose, and bore a significant positive relationship to the systemic GIP level in the early postprandial period. In terms of absolute amounts, portoarterial concentration gradients increased postprandially. Insulin release was significantly the highest after intake of the 14% protein diet. The gastrin response was significantly correlated to the amount of protein. Similarly the release of glucagon and somatostatin tended to increase with increasing dietary amount, but differences failed to reach significance (P less than 0.05), except for glucagon 2 h after the meal. There were very close relationships between the hourly amounts of alpha-amino nitrogen absorbed and gastrin and glucagon production, as between insulin and PP secretions. From the present results, the induction of physiological increments of plasma peptide concentration in 60-kg pigs would require infusion rates of about 50-250 micrograms/h for insulin, 1-4 micrograms/h for gastrin 17, 5-10 micrograms/h for glucagon and somatostatin, and 5-50 micrograms/h for PP.     

Amylin receptor blockade stimulates food intake in rats

Amylin is postulated to act as a hormonal signal from the pancreas to the brain to inhibit food intake and regulate energy reserves. Amylin potently reduces food intake, body weight, and adiposity when administered systemically or into the brain. Whether selective blockade of endogenous amylin action increases food intake and adiposity remains to be clearly established. In the present study, the amylin receptor antagonist acetyl-[Asn(30), Tyr(32)] sCT-(8-32) (AC187) was used to assess whether action of endogenous amylin is essential for normal satiation to occur. Non-food-deprived rats received a 3- to 4-h intravenous infusion of AC187 (60-2,000 pmol.kg(-1).min(-1)), either alone or coadministered with a 3-h intravenous infusion of amylin (2.5 or 5 pmol.kg(-1).min(-1)) or a 2-h intragastric infusion of an elemental liquid diet (4 kcal/h). Infusions began just before dark onset. Food intake and meal patterns during the first 4 h of the dark period were determined from continuous computer recordings of changes in food bowl weight. Amylin inhibited food intake by approximately 50%, and AC187 attenuated this response by approximately 50%. AC187 dose-dependently stimulated food intake (maximal increases from 76 to 171%), whether administered alone or with an intragastric infusion of liquid diet. Amylin reduced mean meal size and meal frequency, AC187 attenuated these responses, and AC187 administration alone increased mean meal size and meal frequency. These results support the hypothesis that endogenous amylin plays an essential role in reducing meal size and increasing the postmeal interval of satiety.