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.     

The influence of ambient temperature and the energy and protein content of food on nitrogenous excretion in the Egyptian fruit bat (Rousettus aegyptiacus)

The diets of frugivorous and nectarivorous vertebrates contain much water and generally have high energy but low protein contents. Therefore, we tested the prediction that to save energy under conditions of high energy demands and high water intake, frugivorous Egyptian fruit bats (Rousettus aegyptiacus) will increase both the absolute quantity and the proportion of ammonia in their urine. We also examined whether such changes occur when protein intake is low and water intake is high. We did three feeding trials. In trials 1 and 2, bats were fed one of four liquid diets containing constant soy protein concentrations but varying in sucrose concentration and were kept at ambient temperatures (T(a)) of 30 degrees Celsius and 12 degrees Celsius, respectively. In trial 3, bats were kept at Ta=12 degrees Celsius and fed one of four liquid diets with equal sucrose concentrations but varying protein concentrations. In trial 1, food intake at a sucrose concentration of 256 mmol/kg H(2)O was initially high but decreased to a constant rate with further increases in sucrose concentration, while in trial 2, food intake decreased exponentially with increasing sucrose concentration. As predicted, at 12 degrees Celsius with varying sucrose concentration, both the absolute quantity and the fraction of ammonia in the bats' urine increased significantly with food intake (P<0.02), while the absolute quantity of urea and the fraction of urea nitrogen excreted decreased significantly with food intake (P<0.03). Varying sucrose concentration had no significant effect on nitrogen excretion at Ta=30 degrees Celsius. Varying protein concentration had no significant effect on nitrogen excretion at Ta=12 degrees Celsius. We suggest that Egyptian fruit bats can increase ammonia excretion in response to increased energetic demands, and we calculate that they can save energy equal to approximately 2% of their daily metabolic rate by doing so.     

Correlation of the plasma tyrosine to phenylalanine ratio with energy intake in self-selecting weanling rats

The relationship between changes in blood plasma amino acids and the quantity of protein and energy self-selected by the weanling rat, simultaneously offered two diets varying only in gluten (15 and 55%) concentration, was examined. Gluten and energy intakes were manipulated by additions of lysine, arginine or ammonia to gluten. In two experiments groups of ten weanling rats were fed the diets for a two week or four week period and food intake selection recorded. Blood samples were obtained between 0900–1100 hr at the end of the two week or four week period. Correlation coefficients of protein intake with the plasma TRP/NAA (Tyr+Phe+Leu+Val+Ile) ratios were ?0.97 and ?0.98, and of energy intake with TYR/PHE ratios were 0.77 and 0.70 in experiments 1 and 2, respectively. It is suggested that the plasma TRP/NAA and TYR/PHE ratios reflect the mechanisms regulating protein and energy intakes, respectively.     

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.     

TrkB receptor signaling in the nucleus tractus solitarius mediates the food intake-suppressive effects of hindbrain BDNF and leptin

Brain-derived neurotrophic factor (BDNF) and TrkB receptor signaling contribute to the central nervous system (CNS) control of energy balance. The role of hindbrain BDNF/TrkB receptor signaling in energy balance regulation is examined here. Hindbrain ventricular BDNF suppressed body weight through reductions in overall food intake and meal size and by increasing core temperature. To localize the neurons mediating the energy balance effects of hindbrain ventricle-delivered BDNF, ventricle subthreshold doses were delivered directly to medial nucleus tractus solitarius (mNTS). mNTS BDNF administration reduced food intake significantly, and this effect was blocked by preadministration of a highly selective TrkB receptor antagonist {[N2-2-2-Oxoazepan-3-yl amino]carbonyl phenyl benzo (b)thiophene-2-carboxamide (ANA-12)}, suggesting that TrkB receptor activation mediates hindbrain BDNF's effect on food intake. Because both BDNF and leptin interact with melanocortin signaling to reduce food intake, we also examined whether the intake inhibitory effects of hindbrain leptin involve hindbrain-specific BDNF/TrkB activation. BDNF protein content within the dorsal vagal complex of the hindbrain was increased significantly by hindbrain leptin delivery. To assess if BDNF/TrkB receptor signaling acts downstream of leptin signaling in the control of energy balance, leptin and ANA-12 were coadministered into the mNTS. Administration of the TrkB receptor antagonist attenuated the intake-suppressive effects of leptin, suggesting that mNTS TrkB receptor activation contributes to the mediation of the anorexigenic effects of hindbrain leptin. Collectively, these results indicate that TrkB-mediated signaling in the mNTS negatively regulates food intake and, in part, the intake inhibitory effects of leptin administered into the NTS.     

An investigation of factors controlling food intake in Arctic charr, Salvelinus alpinus L.

Digestibility values were determined for diets of varying protein content fed to Arctic charr. The use of these values, in conjunction with food intake data made possible the study of the effects of various parameters on the control of food consumption. Dietary energy content may be more important than protein content in regulating consumption. The regulation of food intake may be partially mediated through factors influencing gastric emptying coupled with mechanisms monitoring dietary metabolizable energy.     

Phenotypic flexibility in digestive system structure and function in migratory birds and its ecological significance

Birds during migration must satisfy the high energy and nutrient demands associated with repeated, intensive flight while often experiencing unpredictable variation in food supply and food quality. Solutions to such different challenges may often be physiologically incompatible. For example, increased food intake and gut size are primarily responsible for satisfying the high energy and nutrient demands associated with migration in birds. However, short-term fasting or food restriction during flight may cause partial atrophy of the gut that may limit utilization of ingested food energy and nutrients. We review the evidence available on the effects of long- and short-term changes in food quality and quantity on digestive performance in migratory birds, and the importance of digestive constraints in limiting the tempo of migration in birds. Another important physiological consequence of feeding in birds is the effect of diet on body composition dynamics during migration. Recent evidence suggests that birds utilize and replenish both protein and fat reserves during migration, and diet quality influences the rate of replenishment of both these reserves. We conclude that diet and phenotypic flexibility in both body composition and the digestive system of migratory birds are important in allowing birds to successfully overcome the often-conflicting physiological challenges of migration.     

CNS melanocortin system involvement in the regulation of food intake

Accumulating evidence indicates that the central melanocortin (MC) system plays a key role in the regulation of food intake and energy balance. This evidence includes findings that either spontaneous genetic mutations or targeted gene deletions that impair melanocortin signaling cause disrupted food intake and body-weight control. In addition, expression of the mRNA that encodes the endogenous agonists and antagonists for CNS melanocortin receptors is regulated by changes in energy balance and body-adiposity signals. Finally, administration of both natural and synthetic ligands to MC receptors produces changes in food intake. The data collectively suggest a critical role for melanocortin signaling in the control of energy balance.     

Nutritional Correlates of Population Density Across Habitats and Logging Intensities in Redtail Monkeys (Cercopithecus ascanius)1

Food resources are arguably the most common limiting factor for most species, yet little is known about how food quantity and quality interact to determine the size and distribution of wildlife populations. Frugivores may be limited by food quality since fruits, unlike leaves, are typically low in protein and minerals. Understanding the factors influencing frugivore population dynamics is particularly important due to rapid habitat loss and the need to construct informed management plans. Therefore, this study used redtail monkeys in Kibale National Park, Uganda as a model frugivore to (1) compare nutrient intake, reproduction, and habitat use patterns for three redtail groups in an unlogged and heavily logged area; and (2) examine relationships between nutrient intake and redtail population densities across five habitats. Feeding time and intake of crude protein, lipids, and minerals were higher in diets consumed by groups in unlogged areas than heavily logged areas. Intake of both copper and sodium intake was below NRC requirement levels suggested for macaques. Food availability in the unlogged areas was 3.5 times higher than the heavily logged area. Across five study sites, absorbable copper and the ratio of copper to caloric intake in redtail diets were significantly related to redtail population density. These results suggest that food quality is an important factor determining frugivore population density in anthropogenically disturbed frugivore habitats. Copper deficiency, which has been associated with population declines of wild herbivores, has the potential to be a key factor limiting densities of frugivores in tropical habitats.     

Obesity: the role of hypothalamic AMP-activated protein kinase in body weight regulation

Obesity is rapidly increasing and is of great public health concern worldwide. Although there have been remarkable developments in obesity research over the past 10 years, the molecular mechanism of obesity is still not completely understood. Body weight results from the balance between food intake and energy expenditure. Recent studies have found that hypothalamic AMP-activated protein kinase plays a key role in regulating these processes. Leptin, insulin, glucose and alpha-lipoic acid have been shown to reduce food intake by lowering hypothalamic AMP-activated protein kinase activity, whereas ghrelin and glucose depletion increase food intake by increasing hypothalamic AMP-activated protein kinase activity. In addition, this enzyme plays a role in the central regulation of energy expenditure. These findings indicate that hypothalamic AMP-activated protein kinase is an important signal molecule, which integrates nutritional and hormonal signals and modulates feeding behavior and energy expenditure.     

Modulation of leptin resistance by protein tyrosine phosphatases

Leptin plays a central role in weight control by suppressing food intake and increasing energy expenditure. The concept of leptin resistance emerged to explain the seemingly paradoxical elevated leptin levels in obesity. Recent discoveries reveal that protein tyrosine phosphatases are key players in leptin resistance by globally suppressing leptin signaling.     

The nutritional value of rat diets of differing energy and protein levels when subjected to physical processing

4 diets formulated to contain 8.5, 10.0, 11.5 and 12.5 MJ/kg metabolizable energy and 85, 133, 192 and 250 g/kg of protein respectively were prepared in 3 physical forms: meal, reground pellets or reground expanded and fed to growing rats from 28 to 56 days of age. Food intake was increased by pelleting and expanding in lower energy diets, whereas these differences tended to disappear in the higher energy diets. Growth and food conversion efficiencies showed a similar pattern, with the greatest differences evident in the low energy diets. Male rats showed greater differences than females in all parameters measured. Expanding the diet improved the microbiological status over pelleting both being superior to unprocessed meal. Measurements of digestible and metabolizable energy values of the 8.5 and 12.5 MJ/kg diets revealed consistent decreases in energy availability following processing. This suggested that the observed growth responses were due mainly to increased food intake coupled with increased nitrogen retention.     

Three Months of High-Fructose Feeding Fails to Induce Excessive Weight Gain or Leptin Resistance in Mice

High-fructose diets have been implicated in obesity via impairment of leptin signaling in humans and rodents. We investigated whether fructose-induced leptin resistance in mice could be used to study the metabolic consequences of fructose consumption in humans, particularly in children and adolescents. Male C57Bl/6 mice were weaned to a randomly assigned diet: high fructose, high sucrose, high fat, or control (sugar-free, low-fat). Mice were maintained on their diets for at least 14 weeks. While fructose-fed mice regularly consumed more kcal and expended more energy, there was no difference in body weight compared to control by the end of the study. Additionally, after 14 weeks, both fructose-fed and control mice displayed similar leptin sensitivity. Fructose-feeding also did not change circulating glucose, triglycerides, or free fatty acids. Though fructose has been linked to obesity in several animal models, our data fail to support a role for fructose intake through food lasting 3 months in altering of body weight and leptin signaling in mice. The lack of impact of fructose in the food of growing mice on either body weight or leptin sensitivity over this time frame was surprising, and important information for researchers interested in fructose and body weight regulation.     

Oxygen Consumption Constrains Food Intake in Fish Fed Diets Varying in Essential Amino Acid Composition

Compromisation of food intake when confronted with diets deficient in essential amino acids is a common response of fish and other animals, but the underlying physiological factors are poorly understood. We hypothesize that oxygen consumption of fish is a possible physiological factor constraining food intake. To verify, we assessed the food intake and oxygen consumption of rainbow trout fed to satiation with diets which differed in essential amino acid (methionine and lysine) compositions: a balanced vs. an imbalanced amino acid diet. Both diets were tested at two water oxygen levels: hypoxia vs. normoxia. Trout consumed 29% less food under hypoxia compared to normoxia (p<0.001). Under both hypoxia and normoxia trout significantly reduced food intake by 11% and 16% respectively when fed the imbalanced compared to the balanced amino acid diet. Oxygen consumption of the trout per unit body mass remained identical for both diet groups not only under hypoxia but also under normoxia (p>0.05). This difference in food intake between diets under normoxia together with the identical oxygen consumption supports the hypothesis that food intake in fish can be constrained by a set-point value of oxygen consumption, as seen here on a six-week time scale.     

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.     

Amygdala, an important regulator for food intake

Amygdala plays a critical role in the regulation of emotional behavior and food intake. Neuropeptides are short chains of amino acids secreted by neurons as intercellular messengers, which regulate different functions such as emotion, food intake, learning and memory. In this review, we summarize the recent progress on the regulation of food intake by amygadala, which is mediated by those neuropeptides known to be critical in the regulation of this process.     

EFFECTS OF LYSINE AND THREONINE FORTIFICATION OF BREAD DURING GESTATION AND LACTATION ON OFFSPRING BRAIN LIPID DEVELOPMENT

Abstract– Offspring brain lipid development has been studied following the amino acid fortification of wheat diet fed to pregnant and lactating rats. Comparisons are made with a 13% casein diet which contains a similar quantity of protein of known high quality, with a 26% casein diet, and with a standard laboratory diet. Increased maternal energy intake was found, particularly during lactation, with protein quality improvement. Offspring of mothers receiving the unsupplemented bread diet had lower total brain cholesterol, phospholipid, cerebroside-sulfatide, and (for 4 of the 5 other diets) ganglioside-NANA levels in comparison to offspring whose mothers received the other diets. Brain cerebroside-sulfatide and cholesterol concentrations were also lower in the offspring whose mothers received the unsupplemented bread, suggesting impaired myelin formation. Phospholipid and ganglioside-NANA concentrations were not lower. Fortification of the bread diet with lysine resulted in increases in both the total levels and concentrations of cerebroside-sulfatide and cholesterol. When both lysine and threonine were added, the cerebroside-sulfatide and cholesterol levels and concentrations were similar to or greater than values for the two casein diets and the standard laboratory diet. The 26% casein diet did not result in higher lipid values than obtained with the 13% casein diet. This study demonstrates the adequacy of amino acid supplementation of a maternal cereal protein diet in allowing normal offspring brain lipid development.     

赤腹松鼠能量代谢和营养需要的初步研究

在饲养条件下,赤腹松鼠(Callosciurus erythraeus)每天摄入干物质为7.06—9.91克/只,摄入能最为525.4—562.2千焦耳/千克~0.75每天每只摄入蛋白质:1.26—2.00克,脂肪0.69—2.79克。松鼠对能量、干物质、蛋白质和脂肪的消化率分别为85.7％—89.3％;84.7％—87.0％;75.9％—82.7％和79.1％—94.0％。赤腹松鼠喜食含脂量高的食物,对脂肪的消化能力高于蛋白质。营造种子含脂量高的多种树种混交林,提供松鼠足够的食物,是防止松鼠危害的有效途径。     

Common Guillemot Uria aalge parents adjust provisioning rates to compensate for low food quality

The quantity and quality of food available within the foraging area set important constraints for chick‐rearing birds, but responses to low quality are not well understood. This study explored the potential for parent birds to adjust quantity (feeding rate) and quality (energy content) in chick provisioning, by studying Common Guillemots Uria aalge on Stora Karlsö, Baltic Sea, predominantly utilizing Sprat Sprattus sprattus, during conditions of high food quantity but reduced food quality. Quality is central to reproductive success in this single‐prey loader. From the chick's perspective, provisioning rates should be increased to compensate for low food quality and to fulfil its growing needs with increasing age. However, the high energy cost of flying in Guillemots makes it important for parent birds to minimize commutes to feeding areas. Provisioning parameters were recorded during three dawn‐to‐dusk watches each breeding season from 2005 to 2013, when clupeids, presumably Sprat, constituted 98% of chick diet. Generalized additive mixed models showed that both feeding rate and size of clupeids (a proxy for energy content) varied between years and changed non‐linearly with chick age, but that there was no change within breeding seasons. Chick age and year explained 36% of the variation in feeding rate but only 2% of the variation in the size of clupeids in chick diets. We conclude that parent birds tried to adjust both feeding rate and prey size, but were less successful with the latter. A strong negative correlation was found between annual feeding rates and size of clupeids, evaluated as the differences relative to the baseline year, and adjusted for the effects of chick age. Although the differences between years were small, the relationship indicates a compensation mechanism that does not seem to impact adult survival, and by which increased feeding rates can partly counteract reduced chick energy intake when food quality is low.