Climate change and infectious diseases: What can we expect?

Global climate change, driven by anthropogenic greenhouse gas emissions, is being particularly felt in Canada, with warming generally greater than in the rest of the world. Continued warming will be accompanied by changes in precipitation, which will vary across the country and seasons, and by increasing climate variability and extreme weather events. Climate change will likely drive the emergence of infectious diseases in Canada by northward spread from the United States and introduction from elsewhere in the world via air and sea transport. Diseases endemic to Canada are also likely to re-emerge. This special issue describes key infectious disease risks associated with climate change. These include emergence of tick-borne diseases in addition to Lyme disease, the possible introduction of exotic mosquito-borne diseases such as malaria and dengue, more epidemics of Canada-endemic vector-borne diseases such as West Nile virus, and increased incidence of foodborne illnesses. Risk is likely to be compounded by an aging population affected by chronic diseases, which results in greater sensitivity to infectious diseases. Identifying emerging disease risks is essential to assess our vulnerability, and a starting point to identify where public health effort is required to reduce the vulnerability and exposure of the Canadian population.

Risk assessment strategies for early detection and prediction of infectious disease outbreaks associated with climate change.

A new generation of surveillance strategies is being developed to help detect emerging infections and to identify the increased risks of infectious disease outbreaks that are expected to occur with climate change. These surveillance strategies include event-based surveillance (EBS) systems and risk modelling. The EBS systems use open-source internet data, such as media reports, official reports, and social media (such as Twitter) to detect evidence of an emerging threat, and can be used in conjunction with conventional surveillance systems to enhance early warning of public health threats. More recently, EBS systems include artificial intelligence applications such machine learning and natural language processing to increase the speed, capacity and accuracy of filtering, classifying and analysing health-related internet data. Risk modelling uses statistical and mathematical methods to assess the severity of disease emergence and spread given factors about the host (e.g. number of reported cases), pathogen (e.g. pathogenicity) and environment (e.g. climate suitability for reservoir populations). The types of data in these models are expanding to include health-related information from open-source internet data and information on mobility patterns of humans and goods. This information is helping to identify susceptible populations and predict the pathways from which infections might spread into new areas and new countries. As a powerful addition to traditional surveillance strategies that identify what has already happened, it is anticipated that EBS systems and risk modelling will increasingly be used to inform public health actions to prevent, detect and mitigate the climate change increases in infectious diseases.

High dietary sucrose triggers hyperinsulinemia, increases myocardial beta-oxidation, reduces glycolytic flux and delays post-ischemic contractile recovery.

Although the causal relationship between insulin resistance (IR) and hypertension is not fully resolved, the importance of IR in cardiovascular dysfunction is recognized. As IR may follow excess sucrose or fructose diet, the aim of this study was to test whether dietary starch substitution with sucrose results in myocardial dysfunction in energy substrate utilization and contractility during normoxic and post-ischemic conditions. Forty-eight male Wistar rats were randomly allocated to three diets, differing only in their starch to sucrose (S) ratio (13, 2 and 0 for the Low S, Middle S and High S groups, respectively), for 3 weeks. Developed pressure and rate x pressure product (RPP) were determined in Langendorff mode-perfused hearts. After 30 min stabilization, hearts were subjected to 25 min of total normothermic global ischemia, followed by 45-min reperfusion. Oxygen consumption, beta-oxidation rate (using 1-13C hexanoate and Isotopic Ratio Mass Spectrometry of CO2 produced in the coronary effluent) and flux of non-oxidative glycolysis were also evaluated. Although fasting plasma glucose levels were not affected by increased dietary sucrose, high sucrose intake resulted in increased plasma insulin levels, without significant rise in plasma triglyceride and free fatty acid concentrations. Sucrose-rich diet reduced pre-ischemic baseline measures of heart rate, RPP and non-oxidative glycolysis. During reperfusion, post-ischemic recovery of RPP was impaired in the Middle S and High S groups, as compared to Low S, mainly due to delayed recovery of developed pressure, which by 45 min of reperfusion eventually resumed levels matching Low S. At the start of reperfusion, delayed post-ischemic recovery of contractile function was accompanied by: (i) reduced lactate production; (ii) decreased lactate to pyruvate ratio; (iii) increased beta-oxidation; and (iv) depressed metabolic efficiency. In conclusion, sucrose rich-diet increased plasma insulin levels, in intact rat, and increased cardiac beta-oxidation and coronary flow-rate, but reduced glycolytic flux and contractility during normoxic baseline function of isolated perfused hearts. Sucrose rich-diet impaired early post-ischemic recovery of isolated heart cardiac mechanical function and further augmented cardiac beta-oxidation but reduced glycolytic and lactate flux.

Centrifugation-based isolation of myosin for measurement of its synthesis rate in small muscle samples.

Myosin is involved in muscle mobility which is particularly affected in many pathophysiological situations. It is composed of heavy (MHC) and light (MLC) chains and measurements of its specific fractional synthesis rate (FSR) are scarce, mostly because of difficulties in isolating this protein. Our aim was to isolate pure myosin from small rat gastrocnemius skeletal muscle samples by setting up a procedure compatible with determination of stable isotope incorporation into myosin using mass spectrometry detection, allowing calculation of its FSR. A centrifugation method was compared to a validated but time-consuming elution gel electrophoresis method. Statistical analysis by the Bland and Altman test revealed a tight relationship between both methods (r2 >0.97, p <0.0001). The purity of the myosin fractions using the two procedures was verified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In addition, the centrifugation procedure allowed simultaneous purification of MLC and MHC, whereas the elution gel electrophoresis technique resulted only in MHC isolation. Finally, the FSRs of myosin and MHC were found to be 0.114+/-0.026 and 0.140+/-0.029%/h, respectively (p not significant). In conclusion, the centrifugation method is a useful and reproducible procedure that results in sufficient amounts of pure myosin for reliable determinations of its own synthesis rate in vivo.

Isomerization increases the postprandial oxidation of linoleic acid but not alpha-linolenic acid in men.

Human lipid intake contains various amounts of trans fatty acids. Refined vegetable and frying oils, rich in linoleic acid and/or alpha-linolenic acid, are the main dietary sources of trans-18:2 and trans-18:3 fatty acids. The aim of the present study was to compare the oxidation of linoleic acid, alpha-linolenic acid, and their major trans isomers in human volunteers. For that purpose, TG, each containing two molecules of [1-(13)C]linoleic acid, alpha-[1-(13)C]linolenic acid, [1-(13)C]-9cis,12trans-18:2, or [1-(13)C]-9cis,12cis,15trans-18:3, were synthesized. Eight healthy young men ingested labeled TG mixed with 30 g of olive oil. Total CO(2) production and (13)CO(2) excretion were determined over 48 h. The pattern of oxidation was similar for the four fatty acids, with a peak at 8 h and a return to baseline at 24 h. Cumulative oxidation over 8 h of linoleic acid, 9cis,12trans-18:2, alpha-linolenic acid, and 9cis,12cis,15trans-18:3 were, respectively, 14.0 +/- 4.1%, 24.7 +/- 6.7%, 23.6 +/- 3.3%, and 23.4 +/- 3.7% of the oral load, showing that isomerization increases the postprandial oxidation of linoleic acid but not alpha-linolenic acid in men.

Differential insulin sensitivities of glucose, amino acid, and albumin metabolism in elderly men and women.

Regulation of glucose homeostasis by insulin is modified during aging, but whether this alteration is associated with changes in protein metabolism is less defined. Insulin dose responses of whole body glucose, leucine, and albumin metabolism have been investigated using isotopic dilution of D-[6, 6-(2)H(2)]glucose and L-[1-(13)C]leucine in 14 young (Y; 24.0 +/- 0.9 yr; mean +/- SEM, 20.5 +/- 0.4 kg/m(2)) and 12 healthy elderly subjects (E; 69.4 +/- 0.6 yr; 24.6 +/- 0.8 kg/m(2)) using a euglycemic and euaminoacidemic hyperinsulinemic clamp at two insulin infusion rates of 0.2 and 0.5 mU/kg.min (CL1 and CL2, respectively). Despite significantly higher plasma insulin in E than in Y, the glucose disposal rate was lower in E than in Y at both insulin levels, whereas glucose production was normally suppressed. Whole body protein breakdown was less inhibited by insulin in E than in Y at CL1 (-13.5 +/- 1.4% vs. -8.8 +/- 1.3%, Y vs. E, P < 0.05), but not significantly at CL2 (-22.0 +/- 1.4% vs. -18.8 +/- 1.7%, Y vs. E, P = NS). The albumin synthesis rate was identical and stimulated to the same extent by insulin in groups Y and E. Gender affected basal leucine metabolism, but the response to insulin was similar in both groups. In conclusion, decreased insulin action on glucose disposal is associated with a reduced insulin sensitivity for protein breakdown in healthy elderly subjects at low insulin concentrations. Higher insulin levels compensate for a reduced insulin action on protein metabolism in elderly subjects.

The digestion rate of protein is an independent regulating factor of postprandial protein retention.

To evaluate the importance of protein digestion rate on protein deposition, we characterized leucine kinetics after ingestion of "protein" meals of identical amino acid composition and nitrogen contents but of different digestion rates. Four groups of five or six young men received an L-[1-13C]leucine infusion and one of the following 30-g protein meals: a single meal of slowly digested casein (CAS), a single meal of free amino acid mimicking casein composition (AA), a single meal of rapidly digested whey proteins (WP), or repeated meals of whey proteins (RPT-WP) mimicking slow digestion rate. Comparisons were made between "fast" (AA, WP) and "slow" (CAS, RPT-WP) meals of identical amino acid composition (AA vs. CAS, and WP vs. RPT-WP). The fast meals induced a strong, rapid, and transient increase of aminoacidemia, leucine flux, and oxidation. After slow meals, these parameters increased moderately but durably. Postprandial leucine balance over 7 h was higher after the slow than after the fast meals (CAS: 38 +/- 13 vs. AA: -12 +/- 11, P < 0.01; RPT-WP: 87 +/- 25 vs. WP: 6 +/- 19 micromol/kg, P < 0.05). Protein digestion rate is an independent factor modulating postprandial protein deposition.

Effect of enteral glutamine on leucine, phenylalanine and glutamine metabolism in hypercortisolemic subjects.

The effect of enteral Gln on protein and Gln metabolism was investigated during experimental hypercortisolemia. Four groups of subjects that had received corticosteroids and either enteral Gln (0.5 g x kg(-1) x day(-1) for 2 days) or isonitrogenous Ala-Gly were studied in a fasted or in a fed state. In either state, enteral Gln, compared with Ala-Gly, induced no statistically significant change in the endogenous rate of Leu appearance, an index of proteolysis, Leu oxidation, and nonoxidative Leu disposal, an index of protein synthesis, as studied by kinetics of [1-(13)C]Leu. Similar data were obtained from kinetics of [(2)H(5)]Phe, resulting in an unchanged protein balance in both cases. In contrast, enteral Gln significantly decreased the endogenous rate of Gln appearance and Gln de novo synthesis in the fed state (P < 0.05) as estimated by the kinetics of [(15)N]Gln. This decrease in Gln de novo synthesis induced by Gln could contribute to spare amino acids in hypercatabolic patients.

Protein turnover modifications induced by the protein feeding pattern still persist after the end of the diets.

This study was undertaken to determine whether the protein feeding pattern could induce chronic adaptation of protein turnover. After a 15-day adaptive period, elderly (68 yr) and young (26 yr) women received, for 14 days, a diet providing 200 KJ x kg fat-free mass (FFM)(-1) x day(-1), where the daily protein intake (1.7 g protein x kg FFM(-1) x day(-1)) was either spread over 4 meals in the spread pattern or mainly (80%) consumed at noon in the pulse pattern. One day after the end of the dietary treatment, whole body leucine kinetics were measured by use of a continuous [(13)C]leucine infusion, both in the postabsorptive state and in the same fed state. The pulse pattern was able to induce, in young as in elderly women, a lower postabsorptive leucine oxidation and endogenous leucine flux than the spread pattern and improved the responsiveness of nonoxidative leucine disposal during 4-h oral feeding. Thus the pulse pattern was able to induce chronic regulation of protein metabolism in young as in elderly women.

Lipolysis, fatness, gender and plasma leptin concentrations in healthy, normal-weight subjects.

BACKGROUND: Relationship between plasma leptin and adiposity and gender has been reported in adults. Effects of age on plasma leptin is unclear and regulation of leptin production by white adipose tissue is still poorly understood. OBJECTIVES: To study if age and parameters of lipolysis are related to plasma leptin concentrations. METHODS: Seventy-seven healthy, normal-weight subjects (age range 19-82 y.) had measurements of body composition (18oxygen dilution technique) and of fasting plasma levels of leptin, glycerol, and nonesterified fatty acids (NEFA). RESULTS: Plasma leptin was correlated to NEFA (r = 0.28) and glycerol (r = 0.48) concentrations. The relationship between %fat and plasma leptin was best fitted by an exponential (r2 = 0.82). In multiple regression %fat, body mass index, glycerol, and gender, but not fat mass, age or NEFA contributed independently to the variation in log plasma leptin. Log plasma leptin was higher in women than in men for a given glycerol concentration. CONCLUSION: Adiposity, lipolysis, and gender are related to plasma leptin in healthy humans.

Rapid and accurate 13CO2 isotopic measurement in whole blood: comparison with expired gas.

Determination of 13CO2 enrichment on the CO2 released from blood by acid has been used in situations in which breath sampling is difficult. This method can be improved by measuring this enrichment on the CO2 spontaneously released from blood. Therefore, simultaneous comparisons of 13CO2 content between breath and arterialized blood added with or without acid were performed in 51 samples from human studies, using the statistical method of Bland and Altman (J. M. Bland and D. G. Altman. Lancet 1: 307-310, 1986). Strong relationships exist between the methods (r > 0.99) expressed in atom percent excess (APE). Compared with breath, the acid method overestimates the 13CO2 enrichment (0.318 +/- 0.632 APE x 1,000, P < 0.001). The acid-free method shows similar enrichments to breath (0. 003 +/- 0.522 APE x 1,000, P = 0.97) with good precision and degree of agreement (95% confidence interval 0.15 APE x 1,000). The analysis can be performed up to 5 days after sampling with a good reproducibility. In conclusion, measuring 13CO2 enrichments on the CO2 spontaneously released from blood is feasible, gives identical results to the breath method, and lessens operator manipulations. It allows study of situations in which the breath sampling method is not feasible.

Energy and substrate metabolism during a 42-day bed-rest in a head-down tilt position in humans.

Microgravity-induced changes in body composition (decrease in muscle mass and increase in fat mass) and energy metabolism were studied in seven healthy male subjects during a 42-day bed-rest in a head-down tilt (HDT) position. Resting energy expenditure (REE), fat and glucose oxidation were estimated by indirect calorimetry on days 0, +8 and +40 of the HDT period. Assessments were performed both in post-absorptive conditions and following two identical test meals given at 3-h intervals. Body composition (dual x-ray absorptiometry) was measured on days 0, +27, +42. Mean post-absorptive lipid oxidation decreased from 53 (SEM 8) mg x min(-1) (day 0) to 32 (SEM 10) mg x min(-1) (day 8, P = 0.04) and 36 (SEM 8) mg x min(-1) (day 40, P = 0.06). Mean post-absorptive glucose oxidation rose from 126 (SEM 15) mg x min(-1) (day 0) to 164 (SEM 14) mg x min(-1) (day 8, P = 0.04) and 160 (SEM 20) mg x min(-1) (day 40, P = 0.07). Mean fat-free mass (FFM) decreased between days 0 and 42 [58.0 (SEM 1.8) kg and 55.3 (SEM 1.7) kg, P < 0.01] while fat mass increased without reaching statistical significance. The mean REE decreased from 1688 (SEM 50) kcal x day(-1) to 1589 (SEM 42) kcal x day(-1) (P = 0.056). Changes in REE were accounted for by changes in FFM. Mean energy intake decreased from 2532 (SEM 43) kcal x day(-1) to 2237 (SEM 50) kcal x day(-1) (day 40, P < 0.01) with only a minor decrease in the proportion of fat. We concluded that changes in fat oxidation at the whole body level can be found during HDT experiments. These changes were related to the decrease in FFM and could have promoted positive fat balance hence an increase in fat mass.

Bioelectrical impedance analysis measurements of total body water and extracellular water in healthy elderly subjects.

OBJECTIVE: To address whether: (1) bioelectrical impedance analysis (BIA) can provide precise and accurate estimates of total body water (TBW) and extracellular water (ECW) in healthy elderly subjects, that display age-induced changes in body composition, (2) BIA models are improved by introducing variables related to geometrical body-shape and osmolarity. DESIGN: Cross-validation of available BIA models and models developed in the study. SUBJECTS: 58 healthy elderly subjects (31 women, 27 men, 66.8+/-4.7 y, mean +/- s.d.) MEASUREMENTS: BIA at 5, 50 and 100 kHz, 18O labelled water measurements of TBW, Br measurements of ECW, anthropometric variables, plasma osmolarity. RESULTS: Published BIA models for estimating TBW, entail various degrees of bias. Precise models (SEE of the models 0.8 L at 100 kHz, 1.0 L at 50 kHz) involving height2/resistance, weight, gender, circumferences and plasma osmolarity were established with data from 30 subjects chosen at random. Cross-validation of an independent group (n = 28) showed no bias (-1.5+/-3.2 L at 100 kHz, -1.4+/-3.2 L at 50 kHz, P = NS). CONCLUSION: We conclude that BIA models with increased accuracy and precision for predicting ECW and TBW can be derived in healthy elderly subjects. Repeated measures had a mean difference of 0.2+/-1.2 L.

Gut mucosal protein synthesis in fed and fasted humans.

Fractional protein synthesis rate (FSR) of duodenal mucosa was measured in two groups of six healthy young men, either in the fed state at the end of a 10-day standardized diet or after a 36-h fast. Protein synthesis rate was measured during a 9-h intravenous infusion of [13C]leucine and [2H5]phenylalanine. The fed group also received an intragastric tracer, [2H3]leucine, mixed with the liquid diet. At the end of the tracer infusion, an endoscopy was performed to take duodenal mucosal biopsies. The major results were that 1) duodenal mucosal protein synthesis was high, 48.0 +/- 8.5% (SE)/day by use of intravenous leucine tracer and intracellular leucine enrichment; 2) it was not affected by feeding whatever the tracer or the precursor pool used for the calculations; 3) the two intravenous tracers gave different FSR values; and 4) with the intragastric tracer, FSR was 25-220% of the rate calculated with the intravenous tracer, depending on the precursor pool used for the calculation. Thus absolute values of FSR should be taken with caution, because they depend on the precursor pool chosen, the route of tracer administration, and the tracer itself. However, gut mucosal protein synthesis as assessed by an intravenous tracer is not affected by feeding in humans.

Albumin and fibrinogen syntheses increase while muscle protein synthesis decreases in head-injured patients.

The effect of trauma on protein metabolism was investigated in the whole body, muscle, and liver in severely head-injured patients presenting an acute inflammatory response by comparison to fed control subjects receiving a similar diet. Nonoxidative leucine disposal (an index of whole body protein synthesis) and muscle, albumin, and fibrinogen synthesis were determined by means of a primed, continuous infusion of L-[1-13C]leucine. Nonoxidative leucine disposal increased by 28% in the patients (P < 0.02). Fractional muscle protein synthesis rate decreased by 50% (P < 0.01) after injury. Fractional and absolute fibrinogen synthesis rates were multiplied by two and nine, respectively, after injury (P < 0.001). Albumin levels were lower in patients (25.2 +/- 1.2 g/l, means +/- SE) than in controls (33.7 +/- 1.2 g/l, P < 0.001). However, fractional albumin synthesis rates were increased by 60% in patients (11.4 +/- 1.0%/day) compared with controls (7.3 +/- 0.4%/day, P < 0.01). Therefore, 1) head trauma induces opposite and large changes of protein synthesis in muscle and acute-phase hepatic proteins, probably mediated by cytokines, glucocorticoids, and other stress hormones, and 2) in these patients, hypoalbuminemia is not due to a depressed albumin synthesis.

Influence of protein intake on whole body and splanchnic leucine kinetics in humans.

The influence of the protein content of the meal on protein turnover was investigated in the splanchnic bed and in the remaining parts of the body in humans. Two groups of five subjects consumed every 20 min a liquid formula providing either 1.5 g protein x kg(-1) x day(-1) (P) or no protein (PF). L-[1-(13)C]leucine and L-[5,5,5-(2)H3]leucine were administered by vein and gut, respectively. An open two-pool model was developed to calculate leucine kinetics in both compartments, with the assumption that the enrichment of the tracers incorporated into very low density lipoprotein apolipoprotein B100 at isotopic steady state could reflect the leucine labeling in the splanchnic region. Nonsplanchnic uptake and release of leucine were not significantly different in the two groups. Within the splanchnic area, leucine uptake was 2.1 times higher in the P than in the PF group (P < 0.01), whereas leucine release was reduced but not significantly (-19%) in the P group compared with the PF group. Moreover, data derived from this model showed that protein intake induced an increase in whole body protein synthesis and no change in whole body protein breakdown. Albumin synthesis, as well as its contribution to whole body protein synthesis, was significantly enhanced by protein intake.

Splanchnic and whole-body leucine kinetics in young and elderly men.

Whole-body and splanchnic protein metabolism were determined in six young (mean age: 22.7 y) and six old (68.2 y) men before and during a standardized meal (41.8 kJ/kg) containing 15.6% protein, by using a combination of intravenous ([13C]leucine) and oral ([2H3]leucine) tracers. In the postabsorptive state, leucine flux and oxidation were similar in both groups when corrected for lean body mass (mean +/- SEM: 1.80 +/- 0.09 compared with 1.79 +/- 0.07 mumol.kg-1.min-1 and 0.55 +/- 0.02 compared with 0.49 +/- 0.04 mumol.kg-1.min-1 for young and old men, respectively, NS). The pattern of response to the meal was also similar in young and old men: increased flux and oxidation, decreased protein breakdown, and unchanged protein synthesis. Splanchnic extraction of dietary leucine was twice as high in elderly men (50 +/- 11% compared with 23 +/- 2%, P < 0.05), was inversely related to plasma leucine concentration (r = -0.771, P < 0.01), and was positively related to body mass index (r = 0.861, P < 0.001). In conclusion, in elderly men there is higher leucine extraction by the gut, liver, or both during feeding, which could lead to a lower peripheral availability of dietary leucine.

Slow and fast dietary proteins differently modulate postprandial protein accretion.

The speed of absorption of dietary amino acids by the gut varies according to the type of ingested dietary protein. This could affect postprandial protein synthesis, breakdown, and deposition. To test this hypothesis, two intrinsically 13C-leucine-labeled milk proteins, casein (CAS) and whey protein (WP), of different physicochemical properties were ingested as one single meal by healthy adults. Postprandial whole body leucine kinetics were assessed by using a dual tracer methodology. WP induced a dramatic but short increase of plasma amino acids. CAS induced a prolonged plateau of moderate hyperaminoacidemia, probably because of a slow gastric emptying. Whole body protein breakdown was inhibited by 34% after CAS ingestion but not after WP ingestion. Postprandial protein synthesis was stimulated by 68% with the WP meal and to a lesser extent (+31%) with the CAS meal. Postprandial whole body leucine oxidation over 7 h was lower with CAS (272 +/- 91 micromol.kg-1) than with WP (373 +/- 56 micromol.kg-1). Leucine intake was identical in both meals (380 micromol.kg-1). Therefore, net leucine balance over the 7 h after the meal was more positive with CAS than with WP (P < 0.05, WP vs. CAS). In conclusion, the speed of protein digestion and amino acid absorption from the gut has a major effect on whole body protein anabolism after one single meal. By analogy with carbohydrate metabolism, slow and fast proteins modulate the postprandial metabolic response, a concept to be applied to wasting situations.

Acute postprandial changes in leucine metabolism as assessed with an intrinsically labeled milk protein.

Mechanisms of protein gain during protein feeding have been investigated using a combination of oral and intravenous labeled leucine in healthy young men. The oral labeled leucine was administered as a free oral tracer ([13C]- or [2H3]leucine) added to unlabeled whey protein or as whey protein intrinsically labeled with L-[1-13C]leucine. When the oral tracer was free leucine, it appeared in the plasma more rapidly than the unlabeled leucine derived from the whey protein, and this resulted in an artifactual 88% decrease of protein breakdown. When the oral tracer was protein bound, protein breakdown did not change significantly after the meal. In contrast, nonoxidative leucine disposal (i.e., protein synthesis) was stimulated by 63% by the meal. In conclusion, 1) an intrinsically labeled protein is more appropriate than an oral free tracer to study postprandial leucine kinetics under non-steady-state conditions and 2) protein gain after a single whey protein meal results solely from an increased protein synthesis with no modification of protein breakdown.

Precursor pool for hepatic protein synthesis in humans: effects of tracer route infusion and dietary proteins.

The estimation of the hepatic protein synthesis precursor pool was investigated through the measurement of very low-density lipoprotein (VLDL) apolipoprotein (apo)B100 labeling in healthy volunteers. L-[1-13C]leucine and L-[5,5,5-2H3]leucine were administered intravenously and intragastrically, respectively. Subjects were continuously fed with isoenergetic meals providing either 16% protein or no protein. The labeling of leucine incorporated into VLDL apoB100 (leucine-apoB) was lower than plasma leucine or alpha-ketoisocaproate (KIC) enrichments with the intravenous tracer. By contrast, with the oral tracer, leucine-apoB enrichment was higher than either plasma free leucine or KIC labeling. The KIC and leucine-apoB enrichments relative to plasma leucine enrichment were not affected by protein intake. Albumin or fibrinogen synthesis rates were similar whatever the administration route of the tracer when leucine-apoB was used to indicate the precursor, which was not the case for plasma leucine or KIC. The present data suggest that leucine-apoB enrichment represents a reliable indicator of the hepatic precursor pool for protein synthesis. The effect of dietary protein on the calculated rates of albumin and fibrinogen synthesis is also reported in relation to the choice of the precursor.