Human Metabolic Response Research Articles

Maximizing information from space data resources: a case for expanding integration across research disciplines

Regulatory systems are affected in space by exposure to weightlessness, high-energy radiation or other spaceflight-induced changes. The impact of spaceflight occurs across multiple scales and systems. Exploring such interactions and interdependencies via an integrative approach provides new opportunities for elucidating these complex responses. This paper argues the case for increased emphasis on integration, systematically archiving, and the coordination of past, present and future space and ground-based analogue experiments. We also discuss possible mechanisms for such integration across disciplines and missions. This article then introduces several discipline-specific reviews that show how such integration can be implemented. Areas explored include: adaptation of the central nervous system to space; cerebral autoregulation and weightlessness; modelling of the cardiovascular system in space exploration; human metabolic response to spaceflight; and exercise, artificial gravity, and physiologic countermeasures for spaceflight. In summary, spaceflight physiology research needs a conceptual framework that extends problem solving beyond disciplinary barriers. Administrative commitment and a high degree of cooperation among investigators are needed to further such a process. Well-designed interdisciplinary research can expand opportunities for broad interpretation of results across multiple physiological systems, which may have applications on Earth.

Metabolic Fate of Tea Polyphenols in Humans

Polyphenols, a ubiquitous group of secondary plant metabolites sharing at least one aromatic ring structure with one or more hydroxyl groups, represent a large group of natural antioxidants abundant in fruits, vegetables, and beverages, such as grape juice, wine, and tea, and are widely considered to contribute to health benefits in humans. However, little is yet known concerning their bioactive forms in vivo and the mechanisms by which they may alter our metabolome, which ultimately contribute toward disease prevention. Here we report a study to determine the metabolic fate of polyphenolic components in a Chinese tea (Pu-erh) in human subjects using a metabonomic profiling approach coupled with multivariate and univariate statistical analysis. Urine samples were collected at 0 h, 1 h, 3 h, 6 h, 9 h, 12 h, and 24 h within the first 24 h and once a day during a 6 week period including a 2 week baseline phase, a 2 week daily Pu-erh tea ingestion phase, and a 2 week "wash-out" phase, and they were analyzed by gas chromatography mass spectrometry and liquid chromatography mass spectrometry. The dynamic concentration profile of bioavailable plant molecules (due to in vivo absorption and the hepatic and gut bacterial metabolism) and the human metabolic response profile were measured and correlated with each other. This study demonstrates that the metabonomic strategy will enable us to integrate the overwhelming amount of metabolic end points as a systems' response to the absorption, metabolism, and disposition of a multicomponent botanical intervention system, leading to a direct elucidation of their mechanisms of action.

Acute effects of hydrocortisone on the metabolic response to a glucose load: increase in the first-phase insulin secretion

Several basic science studies support the existence of non-genomic glucocorticoid signaling in pancreas, liver, and adipocytes, but its clinical relevance has not yet been elucidated. This study aimed at investigating the rapid effects of hydrocortisone on the human metabolic response to glucose. In a randomized placebo-controlled crossover study, ten healthy men received an i.v. bolus of 0.6 mg/kg hydrocortisone once and placebo once 4 min before the administration of 330 mg/kg glucose. Cortisol, glucose, insulin, C-peptide, ghrelin, and peptide YY (PYY) levels were measured during the following 3 h. Minimal model analysis was performed for evaluating the metabolic response. Hydrocortisone attenuated the rise in plasma glucose during the initial 15 min following glucose administration (P=0.039), and it led to lower glucose levels during the first 2 h (P=0.017). This was accompanied by enhanced circulating insulin (P=0.02) and C-peptide (P=0.03) levels during the initial 15 min, and a 35% increase in the first-phase beta-cell function (P=0.003). Hydrocortisone decreased PYY concentrations during the initial 30 min (P=0.014), but it did not affect the ghrelin response to glucose. One i.v. bolus of hydrocortisone induces rapid effects on carbohydrate metabolism increasing the first-phase beta-cell function. The modulation of PYY plasma levels suggests the possible non-genomic effects of glucocorticoids on appetite-regulatory hormones.

“Fat adaptation” for athletic performance: the nail in the coffin?

endurance athletes have a high capacity for the oxidation of fat during exercise as a legacy of their training. Therefore, it is intriguing that this capacity can be easily upregulated by the chronic consumption of a low-carbohydrate (<2.5 g·kg−1·day−1), high-fat (∼65–70% of energy) diet.

The effects of pre-warming on the metabolic and thermoregulatory responses to prolonged submaximal exercise in moderate ambient temperatures.

To determine the effects of pre-warming on the human metabolic and thermoregulatory responses to prolonged steady-rate exercise in moderate ambient temperatures and relative humidities [means (SD) 21.7 (2.1) degrees C and 36.7 (5.4)%, respectively], six healthy men each ran at a steady-rate (70% maximal oxygen uptake) on a treadmill until exhausted after being actively pre-warmed (AH), passively pre-warmed (PH), and rested (Cont). Exercise time to exhaustion was significantly reduced following both AH and PH compared to Cont [AH 47.8 (14.0) min, PH 39.6 (16.0) min, Cont 62.0 (8.8) min; P<0.05]. During exercise there were no significant differences in oxygen uptake, total sweat loss, mean skin temperature (T(sk)) and the thermal gradient ( T(re)-T(sk), where T(re) is rectal temperature) following the three conditions. Serum prolactin, plasma catecholamine and plasma free fatty acid concentrations were also similar between all three trials. In contrast, T(re), mean body temperature, heart rate and ratings of perceived exertion were significantly greater during the initial 25 min of exercise following both AH and PH, compared with Cont ( P<0.05). At exhaustion, there were no significant differences in the metabolic and thermoregulatory responses to exercise between the trials. The current findings demonstrate that AH and PH promote a reduction in prolonged submaximal endurance performance under moderate environmental temperatures compared with pre-exercise rest. Such observations appear likely to have been mediated through mechanisms associated with the earlier development of high internal body temperature which resulted in changes in the capacity for heat storage.

Human brain metabolic response to caffeine and the effects of tolerance.

Since there is limited information concerning caffeine's metabolic effects on the human brain, the authors applied a rapid proton echo-planar spectroscopic imaging technique to dynamically measure regional brain metabolic responses to caffeine ingestion. They specifically measured changes in brain lactate due to the combined effects of caffeine's stimulation of glycolysis and reduction of cerebral blood flow. Nine heavy caffeine users and nine caffeine-intolerant individuals, who had previously discontinued or substantially curtailed use of caffeinated products because of associated anxiety and discomforting physiological arousal, were studied at baseline and then during 1 hour following ingestion of caffeine citrate (10 mg/kg). To assess state-trait contributions and the effects of caffeine tolerance, five of the caffeine users were restudied after a 1- to 2-month caffeine holiday. The caffeine-intolerant individuals, but not the regular caffeine users, experienced substantial psychological and physiological distress in response to caffeine ingestion. Significant increases in global and regionally specific brain lactate were observed only among the caffeine-intolerant subjects. Reexposure of the regular caffeine users to caffeine after a caffeine holiday resulted in little or no adverse clinical reaction but significant rises in brain lactate which were of a magnitude similar to that observed for the caffeine-intolerant group. These results provide direct evidence for the loss of caffeine tolerance in the human brain subsequent to caffeine discontinuation and suggest mechanisms for the phenomenon of caffeine intolerance other than its metabolic effects on elevating brain lactate.

Human Cardiovascular and Metabolic Response to Acute, Severe Isovolemic Anemia

Context.—Although concern over the risks of red blood cell transfusion has resulted in several practice guidelines for transfusion, lack of data regarding the physiological effects of anemia in humans has caused uncertainty regarding the blood hemoglobin (Hb) concentration requiring treatment.Objective.—To test the hypothesis that acute isovolemic reduction of blood Hb concentration to 50 g/L in healthy resting humans would produce inadequate cardiovascular compensation and result in tissue hypoxia secondary to inadequate oxygen transport.Design.—Before and after interventional study.Setting.—Academic tertiary care medical center.Participants.—Conscious healthy patients (n=11) prior to anesthesia and surgery and volunteers not undergoing surgery (n=21).Interventions.—Aliquots of blood (450-900 mL) were removed to reduce blood Hb concentration from 131 (2) g/L to 50 (1) g/L [mean (SE)]. Isovolemia was maintained with 5% human albumin and/or autologous plasma. Cardiovascular parameters, arterial and mixed venous oxygen content, oxyhemoglobin saturation, and arterial blood lactate were measured before and after removal of each aliquot of blood. Electrocardiogram and, in a subset, Holter monitor were monitored continuously.Main Outcome Measures.—Critical oxygen delivery (TO2) as assessed by oxygen consumption (O2), plasma lactate concentration, and ST changes on electrocardiogram.Results.—Acute, isovolemic reduction of Hb concentration decreased systemic vascular resistance and TO2 and increased heart rate, stroke volume, and cardiac index (each P<.001). We did not find evidence of inadequate oxygenation: O2 increased slightly from a mean (SD) of 3.07 (0.44) mL of oxygen per kilogram per minute (mL O2·kg−1·min−1) to 3.42 (0.54) Ml O2·kg−1·min−1 (P<.001) and plasma lactate concentration did not change (0.81 [0.11] mmol/L to 0.62 [0.19] mmol/L;P=.09). Two subjects developed significant ST changes on Holter monitor: one apparently related to body position or activity, the other to an increase in heart rate (at an Hb concentration of 46-53 g/L); both occurred in young women and resolved without sequelae.Conclusions.—Acute isovolemic reduction of blood Hb concentration to 50 g/L in conscious healthy resting humans does not produce evidence of inadequate systemic TO2, as assessed by lack of change of O2 and plasma lactate concentration. Analysis of Holter readings suggests that at this Hb concentration in this resting healthy population, myocardial ischemia would occur infrequently.

Human cardiovascular and metabolic response to acute, severe isovolemic anemia: Weiskopf RB, Viele MK, Feiner J, Kelley S, Lieberman J, Noorani M, et al. JAMA 1998;279:217–221

Human cardiovascular and metabolic response to acute, severe isovolemic anemia: Weiskopf RB, Viele MK, Feiner J, Kelley S, Lieberman J, Noorani M, et al. JAMA 1998;279:217–221

Human cardiovascular and metabolic response to acute, severe isovolemic anemia.

Although concern over the risks of red blood cell transfusion has resulted in several practice guidelines for transfusion, lack of data regarding the physiological effects of anemia in humans has caused uncertainty regarding the blood hemoglobin (Hb) concentration requiring treatment. To test the hypothesis that acute isovolemic reduction of blood Hb concentration to 50 g/L in healthy resting humans would produce inadequate cardiovascular compensation and result in tissue hypoxia secondary to inadequate oxygen transport. Before and after interventional study. Academic tertiary care medical center. Conscious healthy patients (n =11) prior to anesthesia and surgery and volunteers not undergoing surgery (n=21). Aliquots of blood (450-900 mL) were removed to reduce blood Hb concentration from 131 (2) g/L to 50 (1) g/L [mean (SE)]. Isovolemia was maintained with 5% human albumin and/or autologous plasma. Cardiovascular parameters, arterial and mixed venous oxygen content, oxyhemoglobin saturation, and arterial blood lactate were measured before and after removal of each aliquot of blood. Electrocardiogram and, in a subset, Holter monitor were monitored continuously. "Critical" oxygen delivery (TO2) as assessed by oxygen consumption (VO2), plasma lactate concentration, and ST changes on electrocardiogram. Acute, isovolemic reduction of Hb concentration decreased systemic vascular resistance and TO2 and increased heart rate, stroke volume, and cardiac index (each P<.001). We did not find evidence of inadequate oxygenation: VO2 increased slightly from a mean (SD) of 3.07 (0.44) mL of oxygen per kilogram per minute (mL O2 x kg(-1) x min[-1]) to 3.42 (0.54) mL O2 x kg(-1) x min(-1) (P<.001) and plasma lactate concentration did not change (0.81 [0.11] mmol/L to 0.62 [0.19] mmol/L; P=.09). Two subjects developed significant ST changes on Holter monitor: one apparently related to body position or activity, the other to an increase in heart rate (at an Hb concentration of 46-53 g/L); both occurred in young women and resolved without sequelae. Acute isovolemic reduction of blood Hb concentration to 50 g/L in conscious healthy resting humans does not produce evidence of inadequate systemic TO2, as assessed by lack of change of VO2 and plasma lactate concentration. Analysis of Holter readings suggests that at this Hb concentration in this resting healthy population, myocardial ischemia would occur infrequently.

The acute effect of moderate alcohol consumption on cardiovascular responses in women.

The purpose of this study was to assess the effects of moderate dose alcohol consumption on human metabolic and cardiovascular responses during submaximal exercise. Ten female subjects participated in two experimental conditions: (1) an alcohol session where the subjects ingested 0.625 g per kg body weight of 80-proof ethyl alcohol (0.25 g/kg of 100% ethanol), and (2) a placebo session. In each session, the subjects exercised on a stationary bicycle at 70% predicted maximum heart rate (HR) for 30 minutes. HR, blood pressure (BP) and oxygen consumption (VO2) were measured at the baseline and at 10, 20 and 30 minute intervals during exercise. Blood lactic acid (BLA) was measured at the baseline and at the end of exercise. Repeated analysis of variance and subsequent comparisons showed that the alcohol session had significantly higher scores for HR, BP, VO2 and BLA than the placebo session (p < .05). These results suggest that during submaximal work, acute moderate alcohol consumption may interfere with aerobic energy metabolism, thus increasing the demand placed upon the cardiovascular system.

Human brain metabolic responses to familiarity during lexical decision

Local cerebral glucose metabolic rate was measured using F18-DG/PET in 11 normal righthanded male volunteers performing two versions of a visual lexical decision task differing only with respect to whether the stimuli were all novel and shown only once, or whether they were all repeated many times. Each subject was also scanned in a resting state (eyes open and ears unplugged). Scalp recordings of cognitive evoked potentials in the same subjects and tasks confirmed that the effects of familiarity were present during the entire 30 min FDG uptake period. The N4 (a left temporoparietal negativity 400 ms after stimulus onset) decreased with repetition, and the P3b (a 600 ms latency parietal positivity) increased. The pattern of metabolic activation was also significantly different between the three experimental conditions. Planned comparisons of the tasks with the resting condition revealed significant relative activations of visual and motor areas. Novel words evoked significantly greater activation in the left and right anterior cingulate gyri and right hippocampal formation than did repeated words in the same task. Relative glucose metabolism in the left angular gyrus was significantly greater to novel words than to resting. Thus, two tasks equated in sensory, motor, and decision processes, but differing in the familiarity of the stimuli, evoke significantly different patterns of brain activation. The patterns observed provided evidence that recent episodic memory for words engages a system that includes the bilateral anterior cingulate gyri, the medial temporal lobe, and the left angular gyrus. © 1994 Wiley-Liss, Inc.

Effects of muscle glycogen and plasma FFA availability on human metabolic responses in cold water

The purpose of this study was to investigate whether simultaneous alterations in the availability of plasma free fatty acids and muscle glycogen would impair the maintenance of thermal balance during cold water immersion in humans. Eight seminude subjects were immersed on two occasions in 18 degrees C water for 90 min or until rectal temperature (Tre) decreased to 35.5 degrees C. Each immersion followed 2.5 days of a specific dietary and exercise regimen designed to elicit low (LOW) or high glycogen levels (HIGH) in large skeletal muscle groups. Nicotinic acid (1.6 mg/kg) was administered for 2 h before and during immersion to inhibit white adipose tissue lipolysis. Biopsies from the vastus lateralis showed that the glycogen concentration before the immersion was significantly lower in LOW than in HIGH (223 +/- 19 vs. 473 +/- 24 mmol glucose units/kg dry muscle). However, the mean rates of glycogen utilization were not significantly different between trials (LOW 0.62 +/- 0.14 vs. HIGH 0.88 +/- 0.15 mmol glucose units.kg-1.min-1). Nicotinic acid dramatically reduced plasma free fatty acid levels in both trials, averaging 127 +/- 21 mumol/l immediately before the immersion. Cold water immersion did not significantly alter those levels. Plasma glucose levels were significantly reduced after cold water immersion to a similar extent in both trials (18 +/- 4%). Mean respiratory exchange ratio at rest and during immersion was greater in HIGH than LOW, whereas there were no intertrial differences in O2 uptake. The calculated average metabolic heat production during immersion tended to be lower (P = 0.054) in LOW than in HIGH (15.3 +/- 1.9 vs. 17.5 +/- 1.9 kJ/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Human metabolic response to exercise

SummaryThe energy necessary to support prolonged submaximal exercise is provided by the aerobic metabolism of carbohydrate and fatty acids. Carbohydrate is stored as glycogen, a polymer of glucose, in the liver and in the skeletal muscles, whereas the fatty acids used by working muscles are mainly derived from triglycerides stored in white adipose tissue cells. The relative contributions of carbohydrate and fatty acids to muscle metabolism depend on the relative exercise intensity. The relative exercise intensity is defined as the oxygen cost of the exercise (V02) expressed as a percentage of the individual's maximum oxygen uptake (% V02 max). At exercise intensities which represent a large % V02 max for an individual, muscle glycogen is the main contributor to muscle metabolism. Fatigue is associated with the depletion of the limited intramuscular glycogen stores. When a carbohydrate‐rich diet is consumed during recovery after exercise, the muscle glycogen stores are increased above theirpre‐exercise concentrations. Thus an exercise and diet regime has been developed to exploit the glycogen supercompensa‐tion phenomenon and so increase endurance capacity.

The human metabolic response to chronic ketosis without caloric restriction: Preservation of submaximal exercise capability with reduced carbohydrate oxidation

To study the effect of chronic ketosis on exercise performance in endurance-trained humans, five well-trained cyclists were fed a eucaloric balanced diet (EBD) for one week providing 35–50 kcal/kg/d, 1.75 g protein/kg/d and the remainder of kilocalories as two-thirds carbohydrate (CHO) and one-third fat. This was followed by four weeks of a eucaloric ketogenic diet (EKD), isocaloric and isonitrogenous with the EBD but providing less than 20 g CHO daily. Both diets were appropriately supplemented to meet the recommended daily allowances for vitamins and minerals. Pedal ergometer testing of maximal oxygen uptake (V̇O 2max) was unchanged between the control week (EBD-1) and week 3 of the ketogenic diet (EKD-3). The mean ergometer endurance time for continuous exercise to exhaustion (ENDUR) at 62%–64% of V̇O 2max was 147 minutes at EBD-1 and 151 minutes at EKD-4. The ENDUR steady-state RQ dropped from 0.83 to 0.72 ( P < 0.01) from EBD-1 to EKD-4. In agreement with this were a three-fold drop in glucose oxidation (from 15.1 to 5.1 mg/kg/min, P < 0.05) and a four-fold reduction in muscle glycogen use (0.61 to 0.13 mmol/kg/min, P < 0.01). Neither clinical nor biochemical evidence of hypoglycemia was observed during ENDUR at EKD-4. These results indicate that aerobic endurance exercise by well-trained cyclists was not compromised by four weeks of ketosis. This was accomplished by a dramatic physiologic adaptation that conserved limited carbohydrate stores (both glucose and muscle glycogen) and made fat the predominant muscle substrate at this submaximal power level.

The human metabolic response to chronic ketosis without caloric restriction: Physical and biochemical adaptation

To study the metabolic effects of ketosis without weight loss, nine lean men were fed a eucaloric balanced diet (EBD) for one week providing 35–50 kcal/kg/d, 1.75 g of protein per kilogram per day and the remaining kilocalories as two-thirds carbohydrate (CHO) and one-third fat. This was followed by four weeks of a eucaloric ketogenic diet (EKD)—isocaloric and isonitrogenous with the EBD but providing less than 20 g CHO daily. Both diets were appropriately supplemented with minerals and vitamins. Weight and whole-body potassium estimated by potassium-40 counting ( 40K) did not vary significantly during the five-week study. Nitrogen balance (N-Bal) was regained after one week of the EKD. The fasting blood glucose remained lower during the EKD than during the control diet (4.4 mmol/L at EBD, 4.1 mmol/L at EKD-4, P < 0.01). The fasting whole-body glucose oxidation rate determined by a 13C-glucose primed constant infusion technique fell from 0.71 mg/kg/min during the control diet to 0.50 mg/kg/min ( P < 0.01) during the fourth week of the EKD. The mean serum cholesterol level rose (from 159 to 208 mg/dL) during the EKD, while triglycerides fell from 107 to 79 mg/dL. No disturbance of hepatic or renal function was noted at EKD-4. These findings indicate that the ketotic state induced by the EKD was well tolerated in lean subjects; nitrogen balance was regained after brief adaptation, serum lipids were not pathologically elevated, and blood glucose oxidation at rest was measurably reduced while the subjects remained euglycemic.

Development and analysis of a small animal model simulating the human postburn hypermetabolic response

Growing guinea pigs and mature rats are good models of the human metabolic response to thermal injury demonstrating a dose-response relationship between burn size and metabolic rate, an elevation in metabolic rate related to the stage of convalescence and hypermetabolism that may be altered but not abated by external heating. A 50% total body surface burn must be produced before reliable elevations in metabolic rate are observed. The mature rat is the best of the three animal models and is suitable for evaluation of the mediators and modulators of the hypermetabolic response to thermal injury.

BLOOD SERUM LIPID PATTERNS OF ADOLESCENT BOYS FED CORN OIL, PEANUT OIL, OR SAFFLOWER OIL

ABSTRACTThe objective of the present study was to compare the effects of feeding low‐fat diets to adolescent boys based on safflower oil, corn oil, or peanut oil on the fatty acid composition of several blood lipid fractions. Boys (aged 13–16 yr) were divided into three groups of 4–5 subjects each and fed weighed controlled diets containing 20% of calories from the test fats for 22 days. Fasting blood samples were drawn the morning of the first day of the study and the morning following the last day of controlled feeding. Blood serum was fractionated by column chromatography into phospholipid, cholesterol ester, triglyceride, and free fatty acid fractions. These were methylated and fatty acid composition determined by gas chromatography. In general in all fractions, feeding of corn oil or safflower oil resulted in increases in linoleic (C2=18) acid content and increases in oleic (C2=18) acid content. Peanut oil feeding resulted in decrease or little change in linoleic acid content and increase in oleic acid content. Results of this study suggest that peanut oil would be better classified with such animal fats as butter oil and beef tallow in human metabolic response than with such vegetable oils as corn oil or safflower oil.

Human metabolic responses to hyperthermia during mild to maximal exercise.

Human metabolic responses to hyperthermia during mild to maximal exercise.