Ketone body turnover during and after exercise in overnight-fasted and starved humans

1983 ◽  
Vol 245 (4) ◽  
pp. E318-E325 ◽  
Author(s):  
F. Fery ◽  
E. O. Balasse

The concentration of ketone bodies and their rate of transport (estimated with an infusion of beta-[14C]-hydroxybutyrate) were determined before, during, and after exercise in overnight-fasted and 3- to 5-day-fasted subjects who walked on a treadmill for 2 h at approximately 50% of their VO2max. In overnight-fasted subjects, exercise increased the rate of turnover (+125% after 2 h) and the metabolic clearance rate of ketone bodies whose concentration rose from 0.20 to 0.39 mM. Discontinuation of exercise was associated with a marked increase in ketone levels (+0.73 mM after 30 min of recovery) that was related to a further stimulation of ketogenesis (+19%) and to a marked drop of the metabolic clearance rate to below preexercise values. In sharp contrast with overnight-fasted subjects, starved subjects (with a resting ketone level averaging 5.7 mM) responded to work by a decrease in the turnover rate and in the concentration of ketones, their metabolic clearance rate remaining unchanged. Thus, the response of ketogenesis and muscular ketone uptake to exercise are both markedly influenced by the initial degree of fasting ketosis.

1986 ◽  
Vol 250 (5) ◽  
pp. E495-E501 ◽  
Author(s):  
F. Fery ◽  
E. O. Balasse

This study examines the effects of a 2-h exercise of moderate intensity (50% of VO2 max) on the tracer-determined turnover rate of ketone bodies (KB) in 21 normal subjects fasted for 16 h, 5 days, whose basal ketonemia ranged between 0.09 and 6.16 mM. The KB response observed at the end of exercise is a function of the initial degree of ketosis. When basal ketonemia is below 0.6 mM, exercise enhances ketogenesis (Ra), the amplitude of this process being positively correlated with KB level. There is a concomitant acceleration of the metabolic clearance rate (MCR) of KB attaining 40-50%. When ketonemia exceeds 2.5 mM, the stimulatory effects of exercise on Ra and on MCR become less marked as basal ketonemia rises and are completely abolished or even reversed when initial KB level is higher than 3-4 mM. The pattern of changes in the concentration and in the overall disposal rate of KB were similar to that of Ra. It is suggested that the parallel inhibition of the stimulatory effect of work on hepatic ketogenesis and on muscular extraction of ketones associated with increasing degrees of fasting hyperketonemia has two physiological implications: it maintains the preferential utilization of KB by nonmuscular tissues (presumably the brain) and prevents the development of uncontrolled hyperketonemia, despite the intense catabolic situation created by the combination of exercise and starvation.


1976 ◽  
Vol 156 (2) ◽  
pp. 233-238 ◽  
Author(s):  
R N Barton

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.


1979 ◽  
Vol 82 (3) ◽  
pp. 409-415 ◽  
Author(s):  
C. E. GROSVENOR ◽  
N. S. WHITWORTH

The prolactin concentration in the plasma of lactating rats rose less rapidly and attained a significantly lower plateau level in response to suckling on day 20–21 of lactation than it did on day 13–14 of lactation. Neither differences in suckling stimulation of the older pups nor a higher metabolic clearance rate (MCR) of prolactin were implicated in the reduced prolactin concentration seen in the late-lactating rats. The MCR was, in fact, slightly reduced in both conscious and late-lactating rats anaesthetized with urethane when compared with those in mid-lactation. The MCR of prolactin was not significantly altered by urethane anaesthesia in rats on either day of lactation. However, the secretion rate of prolactin, computed from the MCR multiplied by the equilibrum concentration of prolactin during suckling, was considerably reduced (665 to 392 ng/min) from mid- to late lactation. We conclude from these data that the reduced plasma concentration of prolactin in response to suckling in late lactation is the result of an impairment within the prolactin secretory mechanism.


2003 ◽  
Vol 90 (4) ◽  
pp. 777-786 ◽  
Author(s):  
Jacques Delarue ◽  
Francois Labarthe ◽  
Richard Cohen

The present study examined the effects of a 3-week fish-oil supplementation (6 g/d) on the rate of plasma glucose disappearance (Rd glucose), hepatic glucose production (HGP), carbohydrate oxidation and lipid oxidation during exercise. Six untrained males (23±1 years; 67·6±2·7kg) performed two 90min cycling exercise sessions at 60% of maximal O2 output separated by 20 d. During the 20 d before the first test, they ingested 6g olive oil/d, then 6g fish oil/d during the 20 d before the second test. Plasma glucose fluxes and lipolysis were traced using 6,6-[2H2]glucose and 1,1,2,3,3-[2H5]glycerol respectively. Substrates oxidation was obtained from indirect calorimetry. At rest HGP and the Rd glucose were similar after olive oil and fish oil (1.83 (se 0·05) v. 1·67 (se 0·11) mg/kg per min). During exercise, fish oil reduced the stimulation of both the Rd glucose (5·06 (se 0·23) v. 6·37 (se 0·12) mg/kg per min; P<0·05) and HGP (4·88 (se 0·24) v. 5·91 (se 0·21) mg/kg per min; P<0·05). Fish oil also reduced glucose metabolic clearance rate (6·93 (se 0·29) v. 8·30 (se 0·57) ml/min). Carbohydrate oxidation tended to be less stimulated by exercise after fish oil than after olive oil (12·09 (se 0·60) v. 13·86 (se 1·11) mg/kg per min; NS). Lipid oxidation tended to be more stimulated by exercise after fish oil (7·34 (se 0·45) v. 6·85 (se 0·17) mg/kg per min; NS). Glycaemia, lactataemia, insulinaemia and glucagonaemia were similarly affected by exercise after fish oil and olive oil. Lipolysis at rest was similar after fish oil and olive oil (2·92 (se 0·42) v. 2·94 (se 0·28) μmol/kg per min) and similarly stimulated by exercise (6·42 (se 0·75) v. 6·77 (se 0·72) μmol/kg per min). It is concluded that fish oil reduced the Rd glucose by 26% by reducing glucose metabolic clearance rate, possibly by facilitating fat oxidation, and reduced HGP by 21%, possibly by a feedback mechanism.


1997 ◽  
Vol 154 (1) ◽  
pp. 113-117 ◽  
Author(s):  
M A Pavia ◽  
B Paier ◽  
M I Noli ◽  
K Hagmüller ◽  
A A Zaninovich

Abstract The effect of in vivo administration of cadmium chloride on the pituitary-thyroidal axis was assessed in 200 g body weight Wistar rats. A dose of 2·5 mg/kg body weight was injected i.v. 24 h before the experiments were initiated. Plasma thyroxine (T4) and tri-iodothyronine (T3) concentrations in cadmium-treated rats were significantly (P<0·01) decreased, whereas plasma TSH failed to increase in response to low T4 and T3. However, the TSH response to TRH and the pituitary content of TSH in these rats were both normal. Cadmium induced a significant (P<0·01) decrease in 4-h thyroidal 131I uptake and in thyroid/plasma radioactivity ratio. The in vitro conversion of T4 to T3 in the pituitary was significantly (P<0·01) blocked by cadmium whereas there was no in vivo effect. Parameters of peripheral T4 kinetics in cadmium-treated rats, such as metabolic clearance rate (P<0·01), fractional turnover rate (P<0·01), absolute disposal rate (P<0·05), urinary clearance (P<0·05) and faecal clearance (P<0·05), were all decreased by cadmium. The lack of response of TSH to low plasma T4 and T3 and the normal response to exogenous TRH in this and in other non-thyroidal illness syndromes produced by other pathologies suggest a decreased stimulation of pituitary thyrotrophs by endogenous TRH. Journal of Endocrinology (1997) 154, 113–117


1988 ◽  
Vol 74 (1) ◽  
pp. 41-48 ◽  
Author(s):  
A. M. Umpleby ◽  
D. Chubb ◽  
M. A. Boroujerdi ◽  
P. H. Sonksen

1. The effect of an infusion of sodium β-hydroxybutyrate on leucine and alanine metabolism was investigated in dogs starved for 12 h. To determine whether the metabolic changes produced by this infusion were due to the resultant alkalaemia the effect of an equimolar infusion of sodium bicarbonate was also studied. 2. The sodium β-hydroxybutyrate infusion reduced alanine concentration as a result of a decrease in alanine production rate and an increase in alanine metabolic clearance rate. The sodium bicarbonate infusion induced a small decrease in alanine concentration which was due to an increased metabolic clearance rate. Alanine production rate showed no change. This demonstrates that the fall in alanine concentration after a sodium β-hydroxybutyrate infusion is due both to a ketone-specific inhibitory effect on alanine production rate and an increased metabolic clearance rate caused by the alkalaemia. 3. Leucine concentration was increased after the ketone infusion due to a small increase in production rate and there was a small increase in the rate of leucine incorporation into protein. Alkalaemia had no effect on leucine concentration or metabolism.


1986 ◽  
Vol 251 (2) ◽  
pp. E139-E145 ◽  
Author(s):  
W. K. Waldhausl ◽  
P. Bratusch-Marrain ◽  
S. Gasic ◽  
M. Komjati ◽  
L. Heding

To determine the role of proinsulin on endogenous insulin release, splanchnic output and arterial concentrations of C-peptide were measured in healthy subjects before and during infusion of human (HPI) and porcine (PPI) proinsulin at increasing rates for 70 min each (HPI, 328 and 656 micrograms X m-2 X h-1; PPI, 54, 134, and 268 micrograms/m-2 X h-1), while euglycemia was maintained by variable glucose infusion. By using this approach splanchnic C-peptide output was reduced by human proinsulin infusion from 143 +/- 16 (mean +/- SE) pmol/min to 111 +/- 18 and 75 +/- 11 pmol/min (P = 0.01). Simultaneously, arterial concentrations of C-peptide decreased from 716 +/- 40 pmol/l by 23 and 32%. Similar inhibition was induced by porcine PPI of splanchnic C-peptide output at an infusion rate of 268 micrograms X m-2 X h-1. Mean metabolic clearance rate was 2.7 and 3.7 ml X kg-1 X min-1 for HPI and PPI, respectively. Splanchnic glucose output was almost completely suppressed by human and porcine proinsulin at maximal infusion rates. This effect preceded both inhibition by proinsulin of splanchnic C-peptide output and stimulation of peripheral glucose utilization. We conclude that human and porcine proinsulin suppress endogenous insulin secretion at pharmacological concentrations. The observed constancy of the metabolic clearance rate of HPI demonstrates that its clearance remains a nonsaturable process up to supraphysiological HPI concentrations, while clearance of PPI appears to be subject to saturation. Furthermore, it appears that splanchnic glucose output responds earlier to proinsulin exposure than suppression of C-peptide release or stimulation of peripheral glucose utilization.


1978 ◽  
Vol 44 (1) ◽  
pp. 5-11 ◽  
Author(s):  
E. O. Balasse ◽  
F. Fery ◽  
M. A. Neef

Seven normal subjects fasted for 3 days were exercised for 30 min on a bicycle ergometer at 60 +/- 30% (mean +/- SE) of their maximal aerobic capacity. Rates of transport and oxidation of ketone bodies were determined at rest and during exercise using a primed constant infusion of [14C]acetoacetate. During the initial 7.5 min of exercise, ketone concentration abruptly decreased (-19.4 +/- 3.1%; P less than 0.001) as the result of a 22.2 +/- 7.0% reduction (P less than 0.05) in ketone production rate (Ra) and a 30.4 +/- 7.5% increase (P less than 0.01) in the rate of uptake (Rd) of ketones. As work progressed, blood ketones continued to fall slowly until the 15th min of exercise and thereafter plateaued at a level which was 21.9 +/- 4.1% lower (P less than 0.005) than resting values. During this apparent new steady state, both Ra and Rd were below control values but tended to be equal and to return simultaneously to their preexercise level. The metabolic clearance rate was increased throughout the entire period of exercise, the rise being more marked during the initial 7.5 min (+40.7 +/- 7.5%; P less than 0.01) than at later periods (+19.0 +/- 7.4%; P less than 0.05). Exercise greatly enhanced ketone oxidation which became virtually complete; despite this, the %CO2 derived from ketones, which averaged 17.6 +/- 1.6% at rest, decreased to 10.1 +/- 0.6% (P less than 0.01) after 30 min of work. This indicates that even during the hyperketonemia of fasting, the increased energy needs related to exercise are met primarily by fuels other than ketones.


1969 ◽  
Vol 47 (12) ◽  
pp. 963-968 ◽  
Author(s):  
O. Héroux ◽  
V. M. Petrovic

Thyroid activity was estimated from thyroxine (T4) turnover rate values by using the single injection isotope dilution technique in rats acclimated to 28 °C and 6 °C and fed either a high-bulk diet (Master Laboratory Cubes (MLC)) or a low-bulk thyroxine-free diet (T4F). In cold-acclimated rats, whether fed MLC or T4F, the metabolic clearance rate of thyroxine was faster than in the 28 °C control rats. The plasma thyroxine level was unchanged after cold acclimation in rats fed MLC but was significantly lower in the T4F-fed rats. The product of the metabolic clearance rate and the plasma thyroxine level or the thyroxine turnover rate was significantly higher after cold acclimation in rats fed the commercial chow diet (MLC) than in rats fed the semipurified T4F diet. This result demonstrates that the increased thyroxine turnover rate, previously observed in cold-acclimated rats, can be taken as another example of a diet-dependent change similar to the thyroid hypertrophy, higher resting metabolic rate, and greater fecal excretion of thyroxine, which have all been shown to be diet-dependent and unnecessary once cold acclimation is established.


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