Ketone body metabolism in lean male adults during short-term starvation, with particular reference to forearm muscle metabolism

1990 ◽  
Vol 78 (6) ◽  
pp. 579-584 ◽  
Author(s):  
M. Elia ◽  
S. Wood ◽  
K. Khan ◽  
E. Pullicino
Keyword(s):  
Fatty Acids ◽  
Ketone Bodies ◽  
Muscle Metabolism ◽  
Resting Energy Expenditure ◽  
Nitrogen Excretion ◽  
Whole Body ◽  
O2 Consumption ◽  
Esterified Fatty Acids ◽  
Protein Energy ◽  
Forearm Muscle

1. Thirty-three arteriovenous forearm catheterization studies were carried out in 19 lean subjects starving for 12–14 h(n = 13), 30–36 h (n = 7) and 60–66 h (n = 13). Forearm blood flow was measured in order to calculate the flux of various substrates. At the same time, whole-body oxidation of fat, carbohydrate and protein was calculated using indirect calorimetry and urinary nitrogen excretion. 2. After an overnight fast (12–14 h), whole-body resting energy expenditure was accounted for by the oxidation of protein (15%), carbohydrate (17%) and fat (68%). At 30–36 h and 60–66 h of starvation, essentially all the non-protein energy was derived from the oxidation of fat (directly plus indirectly via ketone bodies). 3. After an overnight fast, acetoacetate and 3-hydroxybutyrate were taken up by forearm muscle at a rate which could account for 5% of the resting O2 consumption of this tissue. As starvation progressed, forearm muscle took up more acetoacetate and released 3-hydroxybutyrate so that the net uptake of ketone bodies was sufficient to account for about 10% of the resting O2 consumption at 30–36 h of starvation and about 20% at 60–66 h of starvation. 4. The uptake of circulating non-esterified fatty acids by forearm muscle accounted for a greater proportion of the forearm O2 consumption than the uptake of ketone bodies at all times studied. The release of lactate and alanine was significantly greater at 36–40 h and 60–66 h of starvation compared with 12–14 h of starvation, but that of glucose did not change significantly. 5. The results suggest that during early starvation: (a) the release of 3-hydroxybutyrate by muscle (36–66 h starvation) contributes to the circulating 3-hydroxybutyrate concentration, (b) the contribution of ketone bodies to oxidative metabolism in lean subjects is variable but considerably lower than the generally accepted values in obese individuals, and (c) the dominant energy source for the resting muscle of lean individuals between 12 and 66 h of starvation is non-esterified fatty acids.

scholarly journals Monoacetoacetin and protein metabolism during parenteral nutrition in burned rats

1985 ◽  
Vol 226 (1) ◽  
pp. 43-50 ◽  
Author(s):  
A Maiz ◽  
L L Moldawer ◽  
B R Bistrian ◽  
R H Birkhahn ◽  
C L Long ◽  
...  
Keyword(s):  
Energy Source ◽  
Ketone Bodies ◽  
Group Iv ◽  
Nitrogen Excretion ◽  
Whole Body ◽  
Protein Breakdown ◽  
Body Protein ◽  
Group Iii ◽  
Protein Energy ◽  
Group I

The effect of intravenous infusion of monoacetoacetin (glycerol monoacetoacetate) as a non-protein energy source was evaluated in burned rats. During 3 days of parenteral nutrition, in which animals received 14 g of amino acids/kg body wt. per day exclusively (group I) or with the addition of isoenergetic amounts (523 kJ/kg per day) of dextrose (group II), a 1:1 mixture of dextrose and monoacetoacetin (group III) or monoacetoacetin (group IV), significant decreases in urinary nitrogen excretion and whole-body leucine oxidation were observed in the three groups given additional non-protein energy as compared with group I. Serum ketone bodies (acetoacetate and 3-hydroxybutyrate) were decreased in rats given dextrose, whereas glucose and insulin increased significantly. Monoacetoacetin-infused animals (group IV) had high concentrations of ketone bodies without changes in glucose and insulin, whereas animals infused with both monoacetoacetin and glucose (group III) showed intermediate values. On day 4 of nutritional support, whole-body L-leucine kinetics were measured by using a constant infusion of L-[1-14C]leucine. In comparison with group I, the addition of dextrose or monoacetoacetin produced a significant decrease in plasma leucine appearance and release from whole-body protein breakdown. Gastrocnemius-muscle protein-synthesis rates were also higher in the three groups receiving additional non-protein energy. These findings suggest that monoacetoacetin can effectively replace dextrose as an intravenous energy source in stressed rats. Both fuels are similar in decreasing weight loss, nitrogen excretion, leucine release from whole-body protein breakdown and oxidation, in spite of differences in energy substrate and insulin concentrations.

scholarly journals Effects of 3-hydroxybutyrate and free fatty acids on muscle protein kinetics and signaling during LPS-induced inflammation in humans: anticatabolic impact of ketone bodies

2018 ◽  
Vol 108 (4) ◽  
pp. 857-867 ◽  
Author(s):  
Henrik H Thomsen ◽  
Nikolaj Rittig ◽  
Mogens Johannsen ◽  
Andreas B Møller ◽  
Jens Otto Jørgensen ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Free Fatty Acids ◽  
Acute Inflammation ◽  
Ketone Bodies ◽  
Muscle Protein ◽  
Initiation Factor ◽  
Whole Body ◽  
Protein Breakdown ◽  
Protein Kinetics ◽  
Nonesterified Fatty Acids

Abstract Background Acute inflammation, and subsequent release of bacterial products (e.g. LPS), inflammatory cytokines, and stress hormones, is catabolic, and the loss of lean body mass predicts morbidity and mortality. Lipid intermediates may reduce protein loss, but the roles of free fatty acids (FFAs) and ketone bodies during acute inflammation are unclear. Objective We aimed to test whether infusions of 3-hydroxybutyrate (3OHB), FFAs, and saline reduce protein catabolism during exposure to LPS and Acipimox (to restrict and control endogenous lipolysis). Design A total of 10 healthy male subjects were randomly tested 3 times, with: 1) LPS, Acipimox (Olbetam) and saline, 2) LPS, Acipimox, and nonesterified fatty acids (Intralipid), and 3) LPS, Acipimox, and 3OHB, during a 5-h basal period and a 2-h hyperinsulinemic, euglycemic clamp. Labeled phenylalanine, tyrosine, and urea tracers were used to estimate protein kinetics, and muscle biopsies were taken for Western blot analysis of protein metabolic signaling. Results 3OHB infusion increased 3OHB concentrations (P < 0.0005) to 3.5 mM and decreased whole-body phenylalanine-to-tyrosine degradation. Basal and insulin-stimulated net forearm phenylalanine release decreased by >70% (P < 0.005), with both appearance and phenylalanine disappearance being profoundly decreased. Phosphorylation of eukaryotic initiation factor 2α at Ser51 was increased in skeletal muscle, and S6 kinase phosphorylation at Ser235/236 tended (P = 0.074) to be decreased with 3OHB infusion (suggesting inhibition of protein synthesis), whereas no detectable effects were seen on markers of protein breakdown. Lipid infusion did not affect phenylalanine kinetics, and insulin sensitivity was unaffected by interventions. Conclusion During acute inflammation, 3OHB has potent anticatabolic actions in muscle and at the whole-body level; in muscle, reduction of protein breakdown overrides inhibition of synthesis. This trial was registered at clinicaltrials.gov as NCT01752348.

scholarly journals The metabolism of circulating non-esterified fatty acids by the whole animal, hind-limb muscle and uterus of pregnant ewes

1983 ◽  
Vol 49 (1) ◽  
pp. 129-143 ◽  
Author(s):  
D. W. Pethick ◽  
D. B. Lindsay ◽  
P. J. Barker ◽  
A. J. Northrop
Keyword(s):  
Fatty Acids ◽  
Hind Limb ◽  
Ketone Bodies ◽  
Gravid Uterus ◽  
Limb Muscle ◽  
Entry Rate ◽  
Esterified Fatty Acids ◽  
Arterial Concentration ◽  
Pregnant Sheep ◽  
Hind Limb Muscle

1. The over-all and regional metabolism of non-esterified fatty acids (NEFA) was studied using a combination of isotopic and arteriovenous-difference techniques.2. There was a common linear relationship, whether stearic, palmitic or oleic acids were used as tracer, between the arterial NEFA concentration and the rates of entry and oxidation.3. Assuming that the tracer used reflected the metabolism of all the NEFA, the total entry rate in fed and fasted pregnant ewes was (mean±SE) 0·44±0·02 and 0·55±0·07 mmol/h per kg body-weight respectively. Oxidation of NEFA contributed (mean±SE) 34±5 and 58±7% to the respiratory carbon dioxide in fed and fasted animals, this accounting for (mean±SE) 46±6 and 59±3% of the respective entry rates.4. Hind-limb muscle both utilized and produced NEFA. The mean gross fractional extraction (calculated from isotopic uptake) was (mean±SE) 9±1%. Gross utilization of any NEFA and appearance of 14CO2 across the muscle were linearly related to the arterial concentration of tracer fatty acid, irrespective of whether this was oleate or stearate. The amount of 14CO2 appearing was consistent with (mean±SE) 54±8% of the CO2 produced by the hind-limb being derived from NEFA oxidation.5. Infused NEFA were partly converted to ketone bodies. Uptake and oxidation in the hind-limb of ketones formed in the liver could account for approximately 20% of the 14CO2 apparently produced in muscle from NEFA. Correction for this reduces the proportion of CO2 derived from NEFA to 43%. There was some indication that ketones were also produced from NEFA in the hind-limb.6. NEFA were not a significant energy source for the gravid uterus.7. An over-all view of energy sources for the whole animal and for hind-limb muscle in normal and fasted pregnant sheep was presented.

scholarly journals Evaluation of the isolated perfused rat hindquarter for the study of muscle metabolism

1971 ◽  
Vol 124 (3) ◽  
pp. 639-651 ◽  
Author(s):  
N. B. Ruderman ◽  
C. R. S. Houghton ◽  
R. Hems
Keyword(s):  
Glucose Uptake ◽  
Nerve Stimulation ◽  
Ketone Bodies ◽  
Synthetic Medium ◽  
Lactate Production ◽  
Muscle Metabolism ◽  
High Rate ◽  
O2 Consumption ◽  
Glycerol Release

1. The metabolic integrity of a new isolated rat hindquarter preparation was studied. The hindquarter was perfused with a semi-synthetic medium containing aged human erythrocytes. More than 95% of the oxidative metabolism of the preparation was due to muscle, the remainder being due to bone, adipose tissue and, where present, skin. 2. Consumption of O2, glucose utilization, glycerol release and lactate production were similar in the presence and in the absence of the skin, indicating that the latter contributed little to the overall metabolism of the preparation. 3. After 40min of perfusion, tissue concentrations of creatine phosphate, ATP and ADP were similar to those found in muscle taken directly from intact animals. The muscle also appeared normal under the electron microscope. 4. The hindquarter did not lose K% to the medium during a 30min perfusion. In the presence of insulin it had a net K% uptake. 5. Insulin caused a sixfold increase in glucose uptake, stimulated O2 consumption by nearly 40% and depressed glycerol release to less than half the control value. 6. Bilateral sciatic-nerve stimulation caused severalfold increases in O2 consumption and lactate production. In the absence of insulin nerve stimulation also enhanced glucose uptake; in the presence of insulin it did not further increase the already high rate of glucose uptake. 7. Rates of lactate production and O2 consumption of the rat hindquarter in vivo and the isolated perfused hindquarter were very similar. 8. Ketone bodies were a major oxidative fuel in vivo of the hindquarter of a rat starved for 2 days. If the acetoacetate and 3-hydroxybutyrate removed by the tissue were completely oxidized, they would have accounted for 77% of the O2 consumption. 9. Acetoacetate accounted for 84% of the ketone bodies removed by the hindquarter in vivo even though its arterial concentration was half that of 3-hydroxybutyrate. 10. Similar rates of acetoacetate and 3-hydroxybutyrate utilization were observed in the perfused hindquarter. 11. Acetoacetate utilization by the perfused hindquarter was not diminished by the addition of either oleate or insulin to the perfusate. 12. Oxidation of glucose to CO2 accounted for less than 4% of the O2 consumed by the perfused hindquarter in both the presence and the absence of insulin. 13. The results indicate that the isolated perfused hindquarter is a useful tool for studying muscle metabolism. They also suggest that ketone bodies, if present in sufficient concentration, are the preferred oxidative fuel of resting muscle.

scholarly journals Effect of ischaemic limb injury on the rates of metabolism of ketone bodies in starved rats

1976 ◽  
Vol 156 (2) ◽  
pp. 233-238 ◽  
Author(s):  
R N Barton
Keyword(s):  
Clearance Rate ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Whole Body ◽  
Metabolic Clearance ◽  
O2 Consumption ◽  
Clearance Rates ◽  
Metabolic Clearance Rate ◽  
Limb Injury ◽  
Blood Ketone Bodies

1. Rats starved for 30h were injected with trace amounts of [3-14C]acetoacetate and β-hydroxy[3-14C]butyrate 1h after ischaemic limb injury in a 20 °C environment, and the concentrations and radioactivities of blood ketone bodies were determined at intervals. 2. Starvation alone raised the rates of production and utilization of β-hydroxybutyrate plus acetoacetate about 3.7-fold, but lowered their metabolic clearance rates by about 50%. In the starved rat ketone-body oxidation could account for up to 30% of whole body O2 consumption. 3. Injury in starved rats lowered the rates of production and utilization of both β-hydroxybutyrate and acetoacetate, the combined fall of about 37% slightly exceeding the concomitant fall in whole-body O2 consumption. The concentration of β-hydroxybutyrate decreased after injury, but its metabolic clearance rate was unaltered; the concentration of acetoacetate rose slightly and its metabolic clearance rate fell.

Exchange of Metabolites in the Leg of Exercising Juvenile Diabetic Subjects

1978 ◽  
Vol 55 (1) ◽  
pp. 73-80 ◽  
Author(s):  
J. Lyngsøe ◽  
J. P. Clausen ◽  
J. Trap-Jensen ◽  
L. Sestoft ◽  
O. Schaffalitzky de Muckadell ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Glucose Uptake ◽  
Ketone Bodies ◽  
Normal Subjects ◽  
Close Correlation ◽  
Juvenile Diabetes ◽  
Control Subjects ◽  
Arterial Blood ◽  
Esterified Fatty Acids ◽  
And Control

1. Exchange of metabolic substrates was studied across the leg at rest and during a bicycle exercise demanding 50% of the maximal oxygen uptake in seven patients with juvenile diabetes and six control subjects. The leg blood flow and the femoral arterial and venous substrate concentrations were measured in the fasting state and, in the diabetic subjects, 24 h after the last administration of insulin. 2. At rest a close correlation was seen in the control subjects between the leg glucose uptake and the arterial insulin concentration. The diabetic subjects, including three patients in whom it could be shown that the insulin concentrations were extremely low, had a resting glucose uptake in the same order of magnitude as the control subjects. The glucose uptake was inversely related to the arterial concentrations of non-esterified fatty acids in both groups. 3. During exercise the glucose uptake increased in both patients and control subjects, but the increase was not related to arterial concentrations of insulin or non-esterified fatty acids. 4. The release of lactate, pyruvate, alanine and glycerol from the leg was not different in diabetic and control subjects neither at rest nor during exercise. 5. The ketonaemia was increased in the diabetic subjects, but the uptake of total ketone bodies was not different in the two groups. No increase in the uptake of total ketone bodies in control and diabetic subjects was found during exercise. The leg uptake of acetoacetate was a function of the substrate load and tended to be higher in diabetic subjects during exercise, when no net uptake of β-hydroxybutyrate was found. 6. The above results suggest that the glucose uptake in human skeletal muscle at rest depends on the concentration of insulin and possibly also of non-esterified fatty acids in arterial blood. In contrast the glucose uptake during exercise is not related to the concentration of insulin or non-esterified fatty acids, which may explain why no differences in this aspect are seen between the leg metabolism of diabetic and normal subjects.

The Relationships between Plasma Substrates and Hormones and the Severity of Injury in 277 Recently Injured Patients

1979 ◽  
Vol 56 (6) ◽  
pp. 563-573 ◽  
Author(s):  
H. B. Stoner ◽  
K. N. Frayn ◽  
R. N. Barton ◽  
C. J. Threlfall ◽  
R. A. Little
Keyword(s):  
Amino Acids ◽  
Fatty Acids ◽  
Injury Severity ◽  
Ketone Bodies ◽  
Total Concentration ◽  
Plasma Concentrations ◽  
Severely Injured ◽  
Esterified Fatty Acids ◽  
Severity Of Injury ◽  
Injured Patients

1. The plasma concentrations of glucose, lactate, amino acids, non-esterified fatty acids, glycerol, ketone bodies, ethanol, cortisol and insulin were measured in patients within a few hours of injury and before treatment. The severity of the injuries was assessed by the Injury Severity Score (ISS) method. 2. Plasma lactate and glucose concentrations both rose significantly with increasing ISS. 3. The concentrations of non-esterified fatty acids and glycerol were greater after moderate (ISS 7–12) than after minor (ISS 1–6) injuries. The glycerol concentrations were no higher and the non-esterified fatty acid concentrations were lower after severe (ISS > 12) than after moderate injuries. The concentrations of total ketone bodies tended to follow those of non-esterified fatty acids and there was a highly significant correlation between them. 4. The total concentration of amino acids was not affected by the severity of injury and there were no systematic changes in the concentrations of individual ones. 5. Plasma insulin concentrations were very variable and not related to severity. A weak correlation with the plasma glucose concentration seen after minor and moderate injuries was lost in the severely injured. 6. The plasma cortisol concentration was positively related to ISS up to ISS 12 but negatively so in the severely injured. 7. Factors such as age, sex and time after last meal were investigated. The most important factor modifying the response was intake of ethanol, which reduced the plasma concentrations of glucose, non-esterified fatty acids and alanine and raised that of lactate as well as the [β-hydroxybutyrate]/[acetoacetate] ratio.

Whole body energy expenditure and fuel oxidation after 2,5-anhydro-D-mannitol administration

1995 ◽  
Vol 268 (1) ◽  
pp. R299-R302 ◽  
Author(s):  
C. R. Park ◽  
R. J. Seeley ◽  
L. Benthem ◽  
M. I. Friedman ◽  
S. C. Woods
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Food Intake ◽  
Ketone Bodies ◽  
Whole Body ◽  
Acid Oxidation ◽  
Metabolic Variables ◽  
Continued Use ◽  
Body Energy ◽  
Lines Of Evidence

The fructose analogue 2,5-anhydro-D-mannitol (2,5-AM) increases food intake in nondeprived rats. Several lines of evidence indicate that vagal signals arising from the liver are critical for this effect. In addition, 2,5-AM decreases plasma glucose and increases lipolysis, resulting in an increase in plasma free fatty acids and ketone bodies. In these respects 2,5-AM produces a state analogous to that observed after food deprivation. Using an indirect calorimeter, we determined that 2,5-AM (300 mg/kg ip) causes a potent and long-lasting decrease in respiratory quotient, indicating a decrease in the fraction of total energy derived from carbohydrate oxidation and an increase in the fraction derived from fatty acid oxidation. These metabolic variables were altered without affecting total metabolic rate. This dose of analogue also stimulated significantly greater food intake than injections of vehicle. These results support the continued use of 2,5-AM as a tool to probe the metabolic controls of food intake.

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