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.     

Portal-drained viscera and hepatic fluxes of branched-chain amino acids do not account for differences in circulating branched-chain amino acids in rats fed arginine-deficient diets

Summary Concentrations and fluxes of amino acids across the portal-drained viscera (PDV) and liver were assessed in rats fed a meal of one of three arginine-deficient diets containing either alanine or the arginine precursors, ornithine or citrulline. A previous report included findings of seven arginine-related amino acids and indicated that only the citrulline-containing diet protected blood arginine concentrations. In the present report we extend these findings and note that the concentrations and fluxes of the non-arginine-related amino acids showed remarkable consistency across diet groups. However, total branched-chain amino acid (BCAA) concentrations of arterial blood were higher in rats fed the - Arg/+ Ala and the - Arg/+ Orn diets than in rats fed the control (+ Arg) diet. The elevated BCAA correlated with higher circulating concentrations of other essential amino acids but were inversely correlated with arginine concentrations. PDV and hepatic fluxes of BCAA were not different across diet groups, indicating that amino acid absorption and hepatic utilization of BCAA were generally comparable across diet groups. Hepatic concentrations of 14 of 22 measured amino acids, including total BCAA, were correlated with their arterial concentrations. The circulating concentrations and net PDV and hepatic fluxes of rats fed the control diet were comparable to our previous observations in fed rats and illustrate the role of the liver in utilization of diet-derived essential amino acids.Abbreviations PDV portal-drained viscera - BCAA branched-chain amino acids - SSA 5-sulfosalicylic acid - PBF portal blood flow - HBF hepatic blood flow - SELSM pooled standard errors of least squares means - TAA total amino acids - NEAA nonessential amino acids - EAA essential amino acids - LNAA large neutral amino acids Mention of a trade name, proprietary product or specific equipment does not constitute a guarantee by the US Department of Agriculture and does not imply its approval to the exclusion of other products that may be suitable.     

Effects of dissolved oxygen on hybridoma cell growth, metabolism, and antibody production kinetics in continuous culture.

The effects of dissolved oxygen concentration (DO) on hybridoma cell physiology were examined in a continuous stirred tank bioreactor with a murine hybridoma cell line (167.4G5.3). Dissolved oxygen concentration was varied between 0% and 100% air saturation. Cell growth and viability, carbohydrate, amino acid, and energy metabolism, oxygen uptake, and antibody production rates were investigated. Cell growth was inhibited at both high and low DO. Cells could grow at 0% DO and maintain viability under a nitrogen atmosphere. Cell viability was higher at low DO. Glucose, glutamine, and oxygen consumption rates changed little at DO above 1% air saturation. However, the metabolic uptake rates changed below 1% DO, where growth became oxygen limited, and a Km value of 0.6% DO was obtained for the specific oxygen uptake rate. The metabolic rates of glucose, glutamine, lactate, and ammonia increased 2-3-fold as the DO dropped from 1% to 0%. Amino acid metabolism followed the same general pattern as that of glutamine and glucose. Alanine was the only amino acid produced. The consumption rates of amino acids changed little above 1% DO, but under anaerobic conditions the consumption rates of all amino acids increased severalfold. Cells obtained most of their metabolic energy from glutamine oxidation except under oxygen limitation, when glucose provided most of the energy. The calculated ATP production rate was only slightly influenced by DO and rose at 0% DO. Antibody concentration was highest at 35% DO, while the specific antibody production rate was insensitive to DO.     

Hindgut fermentation in the wombats: two marsupial grazers

Summary The wombats Vombatus ursinus and Lasiorhinus latifrons have a capacious proximal colon with only a vestigial caecum. The pattern of microbial fermentation in the hindgut of both species was studied in captive animals fed a pelleted straw diet and in wild wombats feeding on their natural winter diets. Digesta pH was low in the stomach but near neutrality along the hindgut, indicating effective absorption and/or buffering of the colonic contents. Initial proportions and production rates of short chain fatty acids in vitro reflected the fermentation of plant cell walls. Proportions of isobutyrate, isovalerate and n-valerate increased towards the distal colon indicating proteolysis and subsequent fermentation of amino acids. The low ammonia content of digesta fluid suggested that ammonia released from these amino acids was absorbed and utilized by the wombats and their gut microbes. Wild wombats had higher concentrations and production rates of short chain fatty acids than captive animals, which was consistent with the higher apparent digestibility of their natural diet. The energy from short chain fatty acids in captive animals was 30–33% of digestible intake. Energy intakes were low and similar to resting metabolic rates estimated for marsupials. Actual resting metabolic rates of the wombats are probably lower than these estimates, and the proportion of energy derived from fermentation substantially higher than the 53–61% estimated in wild wombats. The energy from fermentation clearly enables wombats to utilize diets high in fibre.Abbreviations DEI digestible energy intake - DM dry matter - NDF neutral detergent fibre - SCFA short chain fatty acids - SD standard deviation - SMR standard metabolic rate     

Metabolic development in the liver and the implications of the n-3 fatty acid supply

The n-3 fatty acids contribute to regulation of hepatic fatty acid oxidation and synthesis in adults and accumulate in fetal and infant liver in variable amounts depending on the maternal diet fat composition. Using 2D gel proteomics and matrix-assisted laser desorption/ionization time of flight mass spectrometry, we recently identified altered abundance of proteins associated with glucose and amino acid metabolism in neonatal rat liver with increased n-3 fatty acids. Here, we extend studies on n-3 fatty acids in hepatic metabolic development to targeted gene and metabolite analyses and map the results into metabolic pathways to consider the role of n-3 fatty acids in glucose, fatty acid, and amino metabolism. Feeding rats 1.5% compared with <0.1% energy 18:3n-3 during gestation led to higher 20:5n-3 and 22:6n-3 in 3-day-old offspring liver, higher serine hydroxymethyltransferase, carnitine palmitoyl transferase, and acyl CoA oxidase and lower pyruvate kinase and stearoyl CoA desaturase gene expression, with higher cholesterol, NADPH and glutathione, and lower glycine (P < 0.05). Integration of the results suggests that the n-3 fatty acids may be important in facilitating hepatic metabolic adaptation from in utero nutrition to the postnatal high-fat milk diet, by increasing fatty acid oxidation and directing glucose and amino acids to anabolic pathways.     

β-Karotinisomere in pflanzlichen Futterstoffen sowie ihre Veränderung durch Einflüsse der Werbung,Trocknung, Lagerung und Silierung

Crossbred wethers (22 months old; 46 ± 1.3 kg body weight), with catheters in a hepatic vein, the portal vein and a mesenteric vein and artery, consumed warm (W; bermudagrass hay) or cool season grass hay (C; ryegrass‐wheat) at 1.6% body weight (dry matter basis) in a crossover design experiment. Warm and cool season grasses were 13.6 and 9.9% crude protein, 77 and 66% neutral detergent fibre and 4.6 and 4.0% acid detergent lignin, respectively. Neutral detergent fibre digestibility (70.3 and 77.4%) and digestible energy intake (8.5 and 9.3 mJ/d) were greater (P<0.02) for C than for W, and digestible nitrogen intake (11.5 and 8.0 g/d for W and C, respectively) was greater (P<0.01) for W. Ruminai fluid concentrations of ammonia nitrogen and total volatile fatty acids were not altered by grass source, and acetate: propionate was greater (P<0.02) for W (3.80) than for the C (3.54). Portal‐drained viscera blood flow (118 and 119 1/h; SE 8.0), oxygen consumption (141 and 142 mM/h; SE 3.7), alpha‐amino nitrogen release (13.4 and 13.1 mM/h; SE 3.42), urea nitrogen uptake (22.8 and 22.5 mM/h; SE 4.97), ammonia nitrogen release (14.9 and 15.7 mM/h; SE 3.36), glucose uptake (10.0 and 6.5 mM/h; SE 1.30), propionate release (14.5 and 16.4 mM/h; SE 1.88), lactate release (4.64 and 5.03 mM/h; SE 1.908) and acetate release (54.8 and 55.4 mM/h for W and C, respectively; SE 8.82) were similar between grasses. Energy consumption by the portal‐drained viscera accounted for a slightly greater (P<0.01) percentage of digestible energy intake with W vs C (18.8 vs 17.0%; SE 0.10). In conclusion, with restricted consumption of W or C by mature sheep, grass source had little impact on net flux of oxygen and nutrients across the portal‐drained viscera and splanchnic bed.     

Nitrogen Metabolism of the Human Brain

Cerebral nitrogen metabolism was studied in 29 healthy nonobese volunteers by means of a catheterization technique. Arterial levels and arterial-jugular venous (A-JV) concentration differences for amino acids, urea, ammonia, 5-oxoproline, glucose, and oxygen were measured in the basal, postabsorptive state and during an intravenous infusion of a commercial amino acid solution. In the basal state positive A-JV differences, indicating a net brain uptake, were noted for 12 of 22 amino acids as well as for ammonia. There was no significant net exchange for urea or for 5-oxoproline. During amino acid infusion, resulting in a 150-300% rise in arterial amino acid levels, the brain uptake of isoleucine, leucine, and tyrosine increased significantly, and a similar tendency was seen for most other amino acids. The infusion was accompanied by a 100% rise in arterial ammonia levels and a 10% increase in urea concentration. For ammonia the small positive A-JV difference in the basal state became markedly greater during amino acid infusion, whereas no significant alteration was noted for urea exchange across the brain. The A-JV differences for glucose and oxygen were positive in the basal state and unchanged during the infusion. The present findings demonstrate that in the basal state (a) there is a significant net brain uptake of most amino acids; (b) no single amino acid, urea, or 5-oxoproline is released from the brain; and (c) ammonia uptake occurs both in this state and during an amino acid infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tissue fatty acid deposition is influenced by an interaction of dietary oil source and energy intake level in rats

To investigate the net tissue fatty acid deposition in response to graded levels of energy restriction and modification of diet fatty acid composition, rats were randomly assigned into four dietary groups and fed for 10 weeks diets containing 40% as energy of either fish, safflower, or olive oil, or beef tallow, consumed ad libitum or energy restricted to 85% or 68% of ad libitum intake by reducing diet carbohydrate content. An additional eight rats were killed before the diet regimen, to provide baseline data from which fatty acid deposition rates were calculated. Body weight, and heart, liver and fat mass gains were decreased with energy restriction (P<0.001). Olive oil feeding resulted in higher body weight gain (P < 0.03) than tallow feeding, whereas fish oil feeding was associated with highest (P < 0.007) liver weight and lowest (P < 0.03) fat mass gains. Energy deficit-related differences in the deposition of stearic, linoleic, arachidonic, and docosahexaenoic acids in heart and palmitic and docosahexaenoic acids in liver were dependent on the dietary oil consumed (P < 0.03). Similarly, interactive effects of restricted food intake and dietary oil type were found in the gain of palmitic, stearic, oleic, and linoleic acids in adipose tissue (P < 0.01) when expressed in relation to the amount of each fatty acid consumed. These data suggest that energy intake level can influence the deposition pattern, as well as oxidation rate, of tissue fatty acids as a function of tissue type, fatty acid structure, and dietary fatty acid composition.     

Metabolic Implications of Dietary Trans‐fatty Acids

Dietary trans‐fatty acids are associated with increased risk of cardiovascular disease and have been implicated in the incidence of obesity and type 2 diabetes mellitus (T2DM). It is established that high‐fat saturated diets, relative to low‐fat diets, induce adiposity and whole‐body insulin resistance. Here, we test the hypothesis that markers of an obese, prediabetic state (fatty liver, visceral fat accumulation, insulin resistance) are also worsened with provision of a low‐fat diet containing elaidic acid (18:1t), the predominant trans‐fatty acid isomer found in the human food supply. Male 8‐week‐old Sprague–Dawley rats were fed a 10% trans‐fatty acid enriched (LF‐trans) diet for 8 weeks. At baseline, 3 and 6 weeks, in vivo magnetic resonance spectroscopy (¹H‐MR) assessed intramyocellular lipid (IMCL) and intrahepatic lipid (IHL) content. Euglycemic–hyperinsulinemic clamps (week 8) determined whole‐body and tissue‐specific insulin sensitivity followed by high‐resolution ex vivo ¹H‐NMR to assess tissue biochemistry. Rats fed the LF‐trans diet were in positive energy balance, largely explained by increased energy intake, and showed significantly increased visceral fat and liver lipid accumulation relative to the low‐fat control diet. Net glycogen synthesis was also increased in the LF‐trans group. A reduction in glucose disposal, independent of IMCL accumulation was observed in rats fed the LF‐trans diet, whereas in rats fed a 45% saturated fat (HF‐sat) diet, impaired glucose disposal corresponded to increased IMCL_TA. Neither diet induced an increase in IMCL_soleus. These findings imply that trans‐fatty acids may alter nutrient handling in liver, adipose tissue, and skeletal muscle and that the mechanism by which trans‐fatty acids induce insulin resistance differs from diets enriched with saturated fats.     

Acute cold exposure and the metabolism of glucose and some of its precursors in the liver of the fed and fasted sheep.

Measurements of total body oxygen consumption, visceral and hepatic blood flow, oxygen consumption, exchanges of amino acids, lactate, pyruvate and glucose were made on sheep fed 3--6 h or 21 h before the experiment and exposed for 3 h to a neutral environment (15 degrees C) or a cold environment (0.5 to 4 degrees C with clipped coat and wind speed 2 m.s-1). Recent feeding significantly increasedd the total oxygen consumption and the oxygen consumption of the viscera and liver. No general release of amino acids from the viscera or uptake by the liver after feeding was detected although the arterial plasma concentration of essential amino acids did increase significantly after feeding. The plasma concentration of most non-essential amino acids also increased except that of glycine, which decreased significantly. Cold exposure increased the total oxygen consumption and reduced the respiratory quotient significantly. Release of amino acids from the viscera was stimulated by cold exposure. There was a variable increase in the hepatic uptake of lactate and alanine when the sheep were fasted and cold-exposed. The liver's glucose output doubled and the blood (arterial) glucose concentration significantly increased in the cold.     

The transient responses of hybridoma cells to nutrient additions in continuous culture: II. Glutamine pulse and step changes

The transient and steady-state responses of hybridoma growth and metabolism to glutamine pulse and step changes have been examined. Metabolic quotients are reported for oxygen, glucose, lactate, ammonia, glutamine, alanine, and other amino acids. The specific glutamine consumption rate increased rapidly after all glutamine additions, but the responses of the glucose and oxygen consumption rates and the cell concentration were found to depend on the intial feed glutamine concentration. The glucose consumption rate was 1.4-10.9 times that of glutamine, and serine and branched-chain amino acids were consumed in larger amounts at the higher glucose: glutamine uptake ratios. It was estimated that maintenance accounted for ca. 60% of the cellular ATP requirements at specific growth rates ranging from 0.57 to 0.68 day(-1).     

Energy metabolism by splanchnic tissues of mature sheep fed varying levels of lucerne hay cubes

The objective of this study was to determine the pattern of energy metabolites net flux across the portal-drained viscera (PDV) and total splanchnic tissues (TSP) in mature sheep fed varying levels of lucerne hay cubes. Four Suffolk mature sheep (61.4 ± 3.6 kg BW) surgically fitted with multi-catheters were fed four levels of dry matter intake (DMI) of lucerne hay cubes ranging from 0.4- to 1.6-fold the metabolizable energy (ME) requirements for maintenance. Six sets of blood samples were simultaneously collected from arterial and venous catheters at 30-min intervals. With increasing DMI, apparent total tract digestibility increased linearly and quadratically for dry matter (P < 0.05), quadratically (P < 0.05) with a linear tendency (P < 0.1) for organic matter and tended to increase quadratically (P < 0.1) for NDF. PDV release of volatile fatty acids (VFA) and β-hydroxybutyric acid was relatively low at 0.4 M and then linearly increased (P < 0.05) with increasing DMI. Net PDV flux of non-esterified fatty acids showed curvilinear decrease from 0.4 to 1.2 M and then increased at 1.6 M. The respective proportions of each VFA appearing in the portal blood differed (P < 0.05) with DMI and this difference was more obvious from 0.4 to 0.8 M than from 0.8 to 1.6 M. Heat production, as a percentage of ME intake (MEI), decreased linearly (P < 0.05) with increasing DMI accounting for 37%, 21%, 16% and 13% for PDV and 62%, 49%, 33% and 27% for TSP at 0.4, 0.8, 1.2 and 1.6 M, respectively. As a proportion of MEI, total energy recovery including heat production, decreased linearly with increasing DMI (P < 0.05) accounting for 113%, 83%, 62% and 57% for PDV and 140%, 129%, 86% and 83% for TSP at 0.4, 0.8, 1.2 and 1.6 M, respectively. Regression analysis revealed a linear response between MEI (MJ/day per kg BW) and total energy release (MJ/day per kg BW) across the PDV and TSP, respectively. However, respective contributions of energy metabolites to net energy release across the PDV and TSP were highly variable among treatments and did not follow the same pattern of changes in DMI.     

Partitioning of nutrients in merino ewes. II. Glucose utilization by skeletal muscle, the pregnant uterus and the lactating mammary gland in relation to whole body glucose utilization

The net uptake and oxidation of glucose by leg muscle, pregnant uterus, and lactating mammary gland, together with the rate of irreversible loss and oxidation of glucose in the whole body of Merino ewes are reported. The ewes were fed on either chaffed oaten hay (OH), chaffed lucerne hay (L), or a mixture of chaffed oaten and lucerne hays (OHL). Measurements were made during five different physiological states: dry (nonpregnant), at 94 and 125 days of pregnancy, and at 20 and 50 days after lambing. Whole body glucose irreversible loss was related significantly to intake of metabolizable energy and fleece-free maternal body weight and this relation was the same in dry, pregnant and lactating ewes. The proportion of glucose oxidized in the whole body was unaffected by diet, but was lower in pregnant than in dry or lactating ewes. Some 6% of whole body carbon dioxide (CO2) production was derived from oxidation of glucose, and in ewes eating the OH diet this proportion was lower than for ewes fed on other diets. The proportion of CO2 derived from glucose was lower in pregnant ewes than in dry and lactating ewes. Leg (muscle) glucose uptake was lower in ewes fed on the OH diet than in ewes given the other diets. This arose partly because of decreased blood flow to the leg in ewes fed OH. Muscle glucose uptake, corrected for lactate output, accounted for 20, 44 and 34% of glucose irreversible loss in ewes fed OH, OHL and L respectively. There was no significant effect of physiological state on glucose uptake by leg muscle. The maximum contribution glucose uptake, corrected for output of lactate, could make to leg muscle oxygen consumption was 31% and there were no differences due to diet or physiological state. Uterine glucose uptake was 10.5 mg min-1 kg-1, and was unaffected by diet and stage of pregnancy. Glucose uptake was maintained, despite a decline in blood flow per kilogram of uterus from 399 to 237 ml min-1 kg-1, between 94 and 125 days of pregnancy by an increase in arteriovenous difference of glucose over the same period from 2.8 to 4.4 mg 100 ml-1. Total uptake of glucose by the uterus increased from 26 to 47 mg min-1 between 94 and 125 days of pregnancy. The proportion of glucose irreversible loss accounted for by uterine uptake increased from 46 to 65% between 94 and 125 days, and was greater for ewes fed OH (84%) than L (46%) at 125 days of pregnancy. A maximum of 71% of milk lactose could have been derived directly from glucose; 17% of glucose taken up by the mammary gland was oxidized, contributing to 20% of mammary CO2 output. Mammary glucose uptake was lower in ewes fed OH than in ewes fed the other diets.(ABSTRACT TRUNCATED AT 400 WORDS)     

Substrate utilization by rat stomach in vivo. Arteriovenous differences for glucose, lactate, ketone bodies, fatty acids and glycerol under control and acid-secreting conditions.

Arteriovenous differences for several potential metabolic substrates were measured across the fundic wall of the stomach of rats that had been starved overnight. There was an uptake of glucose and D-3-hydroxybutyrate, but no significant arteriovenous differences for acetoacetate, pyruvate, non-esterified fatty acids and glycerol were apparent. Lactate output represented a substantial fraction of glucose uptake when the arterial lactate concentration was within the resting physiological range, but when the arterial lactate concentration was above 1.3 mM, lactate was taken up by the stomach. Stimulation of acid secretion by pentagastrin did not affect the value of arteriovenous differences. Thus blood flow to the fundic mucosa and substrate metabolism may be similarly enhanced by pentagastrin. It is concluded that metabolism of glucose and D-3-hydroxybutyrate, and to a lesser extent of glutamine and branched-chain amino acids [Anderson & Hanson (1983) Biochem. J. 210, 451-455], could supply energy to power acid secretion.     

Spectrum of effects of dietary long-chain fatty acids on rat intestinal glucose and lipid uptake

Isocaloric modification in the ratio of dietary polyunsaturated-to-saturated fatty acids influences intestinal uptake of actively and passively transported nutrients. This study was undertaken to determine which dietary fatty acid was responsible for these alterations in absorption. Adult female rats were fed isocaloric semisynthetic diets high in palmitic and stearic acids (SFA), oleic acid (OA), linoleic acid (LA), or linolenic acid (LNA). An in vitro technique was used to measure the uptake of varying concentrations of glucose as well as a series of fatty acids and cholesterol. Jejunal uptake of 40 mM glucose was highest in rats fed SFA and lowest in those fed LA; ileal glucose uptake was similar in OA, LA, and LNA, but was lowest in SFA. Jejunal uptake of medium-chain fatty acids (8:0-12:0) was higher in OA than in other diet groups; ileal uptake of medium-chain fatty acids was unaffected by diet. Jejunal and ileal uptake of 18:2 was higher in LNA than in SFA or OA; the uptake of the other long-chain saturated or unsaturated fatty acids was unchanged by diet. The ileal but not the jejunal uptake of cholesterol was increased in LA as compared with SFA or OA, and reduced in LNA as compared with LA. These transport changes were not explained by differences in the animals' food consumption, body weight gain, intestinal mass, or mucosal surface area. We postulate that these diet-induced transport alterations may be mediated via changes in brush border membrane phospholipid fatty acyl composition. Thus, intestinal transport of nutrients may be varied by isocaloric changes in the dietary content of individual fatty acids.     

Dynamic model of the lactating dairy cow metabolism

The whole-animal model described in this paper is intended to be a research model with an intermediary structure between sophisticated and simple cow models. The mechanistic model structure integrates the main metabolic pathways of the lactating dairy cow. Milk yield and related feed intake for varying production potentials were considered to be the driving forces and were empirically defined. The model was designed to explain the main metabolic flows and variations in body reserves associated with the push of nutrients from dry matter intake and their pull by the mammary gland to synthesise milk components throughout lactation. The digestive part of the model uses either known feed unit systems (e.g. PDI system for protein) or published empirical equations for the prediction of digestive flows of organic matter, starch and fatty acids and ruminal volatile fatty acid production. The metabolic sub-system is made up of four tissue compartments (body protein, body lipid, protein in the uterus and triglycerides in the liver) and five circulating metabolites (glucose, amino acids, acetate + butyrate, propionate, and triglycerides and non-esterified fatty acids). A major original aspect of the model is its homeorhetic control system. It was assumed that flows relating to adipose and protein tissue anabolism and catabolism were driven by a couple of linked theoretical hormones controlling mobilisation and anabolism. The evolution in body composition and body weight were outcomes of this control. Another originality of the model is its suitability for milk yields varying from 10 to 50 kg at peak production. This was achieved by homeorhetic control of milk potential acting on several key metabolic flows. Homeostatic regulation was also introduced in order to confine the behaviour of the model within realistic physiological values. For some basic aspects (e.g. Uterine involution, standard kinetics of body protein and fat), it was necessary to build specific databases from the literature and interpret these by meta-analysis. Fairly realistic simulated kinetics were obtained for body composition, liver triglycerides, blood plasma metabolite concentrations, milk protein and fat contents, and also for major groups of milk fatty acids.     

Metabolomics of aerobic metabolism in mice selected for increased maximal metabolic rate

Maximal aerobic metabolic rate (MMR) is an important physiological and ecological variable that sets an upper limit to sustained, vigorous activity. How the oxygen cascade from the external environment to the mitochondria may affect MMR has been the subject of much interest, but little is known about the metabolic profiles that underpin variation in MMR. We tested how seven generations of artificial selection for high mass-independent MMR affected metabolite profiles of two skeletal muscles (gastrocnemius and plantaris) and the liver. MMR was 12.3% higher in mass selected for high MMR than in controls. Basal metabolic rate was 3.5% higher in selected mice than in controls. Artificial selection did not lead to detectable changes in the metabolic profiles from plantaris muscle, but in the liver amino acids and tricarboxylic acid cycle (TCA cycle) metabolites were lower in high-MMR mice than in controls. In gastrocnemius, amino acids and TCA cycle metabolites were higher in high-MMR mice than in controls, indicating elevated amino acid and energy metabolism. Moreover, in gastrocnemius free fatty acids and triacylglycerol fatty acids were lower in high-MMR mice than in controls. Because selection for high MMR was associated with changes in the resting metabolic profile of both liver and gastrocnemius, the result suggests a possible mechanistic link between resting metabolism and MMR. In addition, it is well established that diet and exercise affect the composition of fatty acids in muscle. The differences that we found between control lines and lines selected for high MMR demonstrate that the composition of fatty acids in muscle is also affected by genetic factors.     

Brush border membrane non-esterified fatty acids. Physiological levels and significance for mucosal iron uptake in mouse proximal intestine

Brush border membrane vesicles prepared using divalent cation precipitation methods can contain unphysiological levels of non-esterified fatty acids. Fatty acid production from endogenous lipid during brush border membrane vesicle preparation is effectively prevented by the lipase inhibitor diethyl 4-nitrophenylphosphate plus cooling. Vesicles prepared using this procedure have variable levels of non-esterified fatty acids (range 22-193 nmol mg-1 protein). Changes in non-esterified fatty acid levels in brush border membrane vesicles parallel Fe uptake by vesicles from Fe/ascorbate solutions. Brush border membrane vesicle fatty acids appear to be derived from the diet but hypoxic mice are able to maintain high brush border membrane non-esterified fatty acid levels despite reduced dietary intake. Non-esterified fatty acids in brush border membrane may thus provide a physiological mechanism of mucosal Fe uptake.     

Glucagon-like peptide-2 (GLP-2) increases net amino acid utilization by the portal-drained viscera of ruminating calves

Glucagon-like peptide-2 (GLP-2) increases small intestinal mass and blood flow in ruminant calves, but its impact on nutrient metabolism across the portal-drained viscera (PDV) and liver is unknown. Eight Holstein calves with catheters in the carotid artery, mesenteric vein, portal vein and hepatic vein were paired by age and randomly assigned to control (0.5% bovine serum albumin in saline; n = 4) or GLP-2 (100 μg/kg BW per day bovine GLP-2 in bovine serum albumin; n = 4). Treatments were administered subcutaneously every 12 h for 10 days. Blood flow was measured on days 0 and 10 and included 3 periods: baseline (saline infusion), treatment (infusion of bovine serum albumin or 3.76 μg/kg BW per h GLP-2) and recovery (saline infusion). Arterial concentrations and net PDV, hepatic and total splanchnic fluxes of glucose, lactate, glutamate, glutamine, β-hydroxybutyrate and urea-N were measured on days 0 and 10. Arterial concentrations and net fluxes of all amino acids and glucose metabolism using continuous intravenous infusion of [U¹³-C]glucose were measured on day 10 only. A 1-h infusion of GLP-2 increased blood flow in the portal and hepatic veins when administered to calves not previously exposed to exogenous GLP-2, but after a 10-day administration of GLP-2 the blood flow response to the 1-h GLP-2 infusion was substantially attenuated. The 1-h GLP-2 infusion also did not appreciably alter nutrient fluxes on either day 0 or 10. In contrast, long-term GLP-2 administration reduced arterial concentrations and net PDV flux of many essential and non-essential amino acids. Despite the significant alterations in amino acid metabolism, glucose irreversible loss and utilization by PDV and non-PDV tissues were not affected by GLP-2. Fluxes of amino acids across the PDV were generally reduced by GLP-2, potentially by increased small intestinal epithelial growth and thus energy and amino acid requirements of this tissue. Increased PDV extraction of glutamine and alterations in PDV metabolism of arginine, ornithine and citrulline support the concept that GLP-2 influences intestine-specific amino acid metabolism. Alterations in amino acid metabolism but unchanged glucose metabolism suggests that the growth effects induced by GLP-2 in ruminants increase reliance on amino acids preferentially over glucose. Thus, GLP-2 increases PDV utilization of amino acids, but not glucose, concurrent with stimulated growth of the small intestinal epithelium in post-absorptive ruminant calves.     

High Dietary Calcium Reduces Body Fat Content,Digestibility of Fat,and Serum Vitamin D in Rats

Objective: This study investigated which aspect of energy balance was responsible for the decrease in body fat content of rats fed a high‐calcium, high—dairy protein diet. Research Methods and Procedures: Male Wistar rats were fed a control diet (25% kcal fat, 14% kcal protein from casein, 0.4% by weight calcium) or high‐calcium diet (25% kcal fat, 7% kcal protein from nonfat dry milk, 7% kcal protein from casein, 2.4% calcium) for 85 days. Body weights, digestible energy intakes, energy expenditures, rectal temperatures, body composition, and serum glucose, insulin, free fatty acids, triglycerides, and 1, 25‐dihydroxyvitamin D were measured. Results: Rats fed high‐calcium diet gained significantly less weight than controls and had 29% less carcass fat. Gross energy intake was not significantly different between groups, but digestible energy was 90% of gross energy in the high‐calcium diet compared with 94% in the control diet because of increased fecal excretion of dietary lipid. The difference in digestible energy intake accounted for differences in carcass energy. Body temperatures and energy expenditures of the rats were not different. The high‐calcium diet reduced serum triglycerides by 23% and serum 1, 25‐dihydroxyvitamin D by 86%. Discussion: These results confirm that a high‐calcium diet decreases body weight and fat content due to a lower digestible energy intake caused by increased fecal lipid and a nonsignificant reduction in gross energy intake.