Acutely decreased thermoregulatory energy expenditure or decreased activity energy expenditure both acutely reduce food intake in mice

Despite the suggestion that reduced energy expenditure may be a key contributor to the obesity pandemic, few studies have tested whether acutely reduced energy expenditure is associated with a compensatory reduction in food intake. The homeostatic mechanisms that control food intake and energy expenditure remain controversial and are thought to act over days to weeks. We evaluated food intake in mice using two models of acutely decreased energy expenditure: 1) increasing ambient temperature to thermoneutrality in mice acclimated to standard laboratory temperature or 2) exercise cessation in mice accustomed to wheel running. Increasing ambient temperature (from 21°C to 28°C) rapidly decreased energy expenditure, demonstrating that thermoregulatory energy expenditure contributes to both light cycle (40±1%) and dark cycle energy expenditure (15±3%) at normal ambient temperature (21°C). Reducing thermoregulatory energy expenditure acutely decreased food intake primarily during the light cycle (65±7%), thus conflicting with the delayed compensation model, but did not alter spontaneous activity. Acute exercise cessation decreased energy expenditure only during the dark cycle (14±2% at 21°C; 21±4% at 28°C), while food intake was reduced during the dark cycle (0.9±0.1 g) in mice housed at 28°C, but during the light cycle (0.3±0.1 g) in mice housed at 21°C. Cumulatively, there was a strong correlation between the change in daily energy expenditure and the change in daily food intake (R² = 0.51, p<0.01). We conclude that acutely decreased energy expenditure decreases food intake suggesting that energy intake is regulated by metabolic signals that respond rapidly and accurately to reduced energy expenditure.     

Increased energy expenditure, decreased adiposity, and tissue-specific insulin sensitivity in protein-tyrosine phosphatase 1B-deficient mice

Protein-tyrosine phosphatase 1B (PTP-1B) is a major protein-tyrosine phosphatase that has been implicated in the regulation of insulin action, as well as in other signal transduction pathways. To investigate the role of PTP-1B in vivo, we generated homozygotic PTP-1B-null mice by targeted gene disruption. PTP-1B-deficient mice have remarkably low adiposity and are protected from diet-induced obesity. Decreased adiposity is due to a marked reduction in fat cell mass without a decrease in adipocyte number. Leanness in PTP-1B-deficient mice is accompanied by increased basal metabolic rate and total energy expenditure, without marked alteration of uncoupling protein mRNA expression. In addition, insulin-stimulated whole-body glucose disposal is enhanced significantly in PTP-1B-deficient animals, as shown by hyperinsulinemic-euglycemic clamp studies. Remarkably, increased insulin sensitivity in PTP-1B-deficient mice is tissue specific, as insulin-stimulated glucose uptake is elevated in skeletal muscle, whereas adipose tissue is unaffected. Our results identify PTP-1B as a major regulator of energy balance, insulin sensitivity, and body fat stores in vivo.     

Reduction in postprandial energy expenditure during pregnancy.

Energy expenditure was measured during pregnancy in seven primigravid women at 12-15, 25-28, and 34-36 weeks and after the cessation of lactation. On each occasion the resting metabolic rate and the increase in metabolic rate after ingestion of a liquid test meal were measured by indirect calorimetry. In absolute terms the resting metabolic rate increased steadily during pregnancy but when expressed per unit of body weight no change was found. The energetic response to a mixed constituent meal was significantly reduced by 28% in the middle trimester of pregnancy. These findings suggest a possible maternal adaptation to increase energetic efficiency at a time when the energy demands of the fetus are high.     

Increased thermoregulatory responsiveness in cold adapted but not in hyperthyroid hypermetabolic rats

Cold-adapted (CA) rats, unlike non-adapted (NA) ones, give exaggerated metabolic response to acute cold exposure, with paradoxical "overshoot" core temperature (Tc) rise in the cold, and they also give enhanced hyperthermia to central injection of prostaglandin E1 (PGE1). The adaptation-dependent differences might be explained either by the high thermogenic capacity of peripheral tissues in CA rats or by differences in the central processing of regulatory signals. If high tissue metabolism sufficiently explains the extreme responses of CA animals, other hypermetabolic states (with high resting metabolic rate, RMR), e.g. hyperthyroidism, should also be accompanied by enhanced reactions. In the present study thermoregulatory responses to acute cold exposure or to PGE1 were compared in hypermetabolic CA, similarly hypermetabolic thyroxine-treated (T4) and control non-hypermetabolic NA rats (mean RMR = 8.12, 8.47 and 6.03 W kg(-1), respectively). Cold exposure was followed by paradoxical core temperature (Tc) rise of 0.5 to 0.7 degrees C only in CA rats, but by Tc fall (0.8 to 2.1 degrees C) in NA and T4 animals. Identical central stimuli (PGE1) induced larger elevations of Tc and metabolic rate in CA rats than in similarly hypermetabolic T4 or in non-hypermetabolic NA animals (mean Tc rise of 1.9 degrees C in CA vs. 0.9 degrees C in T4 and 1.0 degrees C in NA rats). Vasodilatation thresholds were also similar in NA and T4, but lowered in CA animals. A hypermetabolic status, per se, does not seem to explain the enhanced thermoregulatory responsiveness of CA animals, adaptation-induced central regulatory changes may be more important for the "overshoot" phenomenon.     

An energy 'sources' and 'fractions' approach to the mechanical energy expenditure problem--III. Mechanical energy expenditure reduction during one link motion

Mechanical energy economy and transformation during one link motion are analyzed on the basis of the theory developed in the previous publications (parts I and II of this series, J. Biomechanics 19, 287-300). The 'compensation coefficient' characterizing mechanical energy economy is introduced. The attempts to estimate MEE using only energy curves and neglecting the powers of real sources of energy implicitly lead to replacement of real force and moment systems by the systems reduced to the centers of mass. But such an unintentional substitution of imaginary sources for real ones, specifically, the reduction of forces acting on the link to the equivalent system, changes estimates of mechanical energy expenditure (MEE). That is why the methods of calculating MEE economy based on the determination of so-called 'quasi-mechanical' work (the sum of the kinetic and potential energy increases per one cycle of motion) are not correct. There are two mechanisms to reduce the MEE using the antiphase fluctuations (corresponding to energy transformations) of the (a) rotational and translational fractions of the total energy (at the expense of the F-sources); (b) potential and kinetic energies (at the expense of the mg-source).     

Effect of whole-body electromyostimulation on energy expenditure during exercise

The application of whole-body electromyostimulation (WB-EMS) in the area of fat reduction and body shaping has become more popular recently. Indeed, some studies prove positive outcomes concerning parameters related to body composition. However, there are conflicting data as to whether EMS relevantly impacts energy expenditure (EE) during or after application. Thus, the main purpose of the study was to determine the acute effect of WB-EMS on EE. Nineteen moderately trained men (26.4 ± 4.3 years) were randomly assigned to a typically used low-intensity resistance exercise protocol (16 minutes) with (85 Hz) and without WB-EMS. Using a crossover design, the same subjects performed both tests after completely recovering within 7 days. Energy expenditure as the primary endpoint of this study was determined by indirect calorimetry. The EE during low-intensity resistance exercise with adjuvant WB-EMS was significantly higher (p = 0.008) than that during the control condition (412 ± 60 vs. 352 ± 70 kcal; effect size; d = 0.92). This study clearly demonstrates the additive effect of WB-EMS on EE in moderately trained subjects during low-intensity resistance exercise training. Although this effect was statistically significant, the fast and significant reductions of body fat observed in recent studies suggest that the effect of WB-EMS on EE may still be underestimated by indirect calorimetry because of the inability of indirect calorimetry to accurately assess EE during "above-steady state conditions." Although from a statistically point of view WB-EMS clearly impacts EE, the relatively small effect did not suggest a broad application of this device in this area. However, taking other positive outcomes of this technology into account, WB-EMS may be a time-saving option at least for subjects unwilling or unable to exercise conventionally.     

Effects on energy expenditure of facial cooling during exercise.

Estimated energy expenditures for men during Arctic manhauling expeditions were 29-33 MJ day-1, higher than those documented for other hard-working groups and exceeding predicted energy costs for such activities. Although physiological effects from generalised cooling were unlikely, cold exposure of the face could have influenced exercise metabolism via autonomic stimulation. This hypothesis was examined by measuring oxygen consumption, energy expenditure, respiratory exchange ratio (R) and cardiovascular changes during rest and exercise, with and without exposure of the face to air at--20 degrees C. Measurements were made in five subjects during 15 min of rest followed by continuous exercise on a cycle ergometer consisting of 15-min periods at 75, 100, 125 and 150 W external work. The cold air caused a profound fall in facial temperatures and small falls in mean skin and rectal temperatures (P less than 0.001). These changes were associated with a small increase in the mean oxygen consumption over all levels of rest and exercise (0.86 l min-1 vs 0.82 l min-1, P less than 0.001) and a corresponding increase in mean energy expenditure (294 W vs 283 W, P less than 0.05). Cold air also caused an increase in mean resting R values (1.00 vs 0.88, P less than 0.01) but a decrease in the mean R value for all levels of exercise (0.85 vs 0.91, P less than 0.05). Pulse rates were unchanged but systolic and diastolic blood pressures were relatively elevated throughout the cold face experiments (P less than 0.001).     

Effect of endurance training on gross energy expenditure during exercise

We compared the effect of endurance exercise training on gross energy expenditure (GEE) during steady-state exercise in 20 younger men (31.2 +/- 0.6 years) and 20 middle-aged men (49.2 +/- 1.1 years). The subjects trained for eight months. The training program consisted of three 45-min walking and jogging exercise sessions per week at an intensity of approximately 60-85% of the heart rate at peak VO2. We administered bicycle ergometer tests at 0, 4, and 8 months into training. Participants exercised at a power output of 100 W for 10 min using a pedaling frequency of 50 rpm. We determined GEE (kcal/min) by measuring the oxygen consumption and respiratory exchange ratio. We found a significant reduction (p less than 0.05) in GEE (0.7-1.3 kcal/min) following 4 months of endurance training in both age groups, with a further reduction (p less than 0.05) noted in only the middle-aged group at month 8. We found no difference (p greater than 0.05) in GEE between the younger and middle-aged men. We conclude that chronic exercise may modify GEE during a submaximal exercise bout and that this adaptation is similar in magnitude in younger and middle-aged men.     

Increased lipolysis and energy expenditure in a mouse model with severely impaired glucagon secretion

Background

Secretion of insulin and glucagon is triggered by elevated intracellular calcium levels. Although the precise mechanism by which the calcium signal is coupled to insulin and glucagon granule exocytosis is unclear, synaptotagmin-7 has been shown to be a positive regulator of calcium-dependent insulin and glucagon secretion, and may function as a calcium sensor for insulin and glucagon granule exocytosis. Deletion of synaptotagmin-7 leads to impaired glucose-stimulated insulin secretion and nearly abolished Ca²⁺-dependent glucagon secretion in mice. Under non-stressed resting state, however, synaptotagmin-7 KO mice exhibit normal insulin level but severely reduced glucagon level.

Methodology/Principal Findings

We studied energy expenditure and metabolism in synaptotagmin-7 KO and control mice using indirect calorimetry and biochemical techniques. Synaptotagmin-7 KO mice had lower body weight and body fat content, and exhibited higher oxygen consumption and basal metabolic rate. Respiratory exchange ratio (RER) was lower in synaptotagmin-7 KO mice, suggesting an increased use of lipid in their energy production. Consistent with lower RER, gene expression profiles suggest enhanced lipolysis and increased capacity for fatty acid transport and oxidation in synaptotagmin-7 KO mice. Furthermore, expression of uncoupling protein 3 (UCP3) in skeletal muscle was approximately doubled in the KO mice compared with control mice.

Conclusions

These results show that the lean phenotype in synaptotagmin-7 KO mice was mostly attributed to increased lipolysis and energy expenditure, and suggest that reduced glucagon level may have broad influence on the overall metabolism in the mouse model.     

Increased oxidative stress during hyperglycemic cerebral ischemia

In this review, we summarize the role of hyperglycemia during cerebral ischemia. Hyperglycemia occurring during experimental and clinical stroke has been associated with increased cerebral damage. Increased oxidative stress resulting from hyperglycemia is believed to contribute to the exacerbated damage. More specifically, superoxide, nitric oxide and peroxynitrite are believed to play an important role in cerebral damage. This also involves increased recruitment of various blood cells to the ischemic zone that contribute to inflammation. We present data from our group and others that demonstrate that free radical production is increased during hyperglycemic stroke in rodents. Recent data suggest that inflammation is an important component of ischemic damage under both normo- and hyperglycemic conditions. We summarize numerous studies that indicate that a variety of antioxidant (inhibition of free radical production, scavenging of free radicals and increasing free radical degradation) and anti-inflammatory strategies decrease cerebral infarction. Finally, we compare the success of some of these strategies in clinical trials compared to the animal models.     

Activity and energy expenditure

The influence of small changes in activity on energy expenditure and hence on energy requirements and energy balance is assessed. Evidence from direct and indirect calorimetry suggests that differences in spontaneous minor activity could readily alter 24-h energy expenditure by as much as 20%. This compares with values in the order of 10% for moderate overfeeding and somewhat less than this during mild cold exposure. Individual variability in 24-h energy expenditure can therefore be accounted for not only by differences in resting metabolism and the thermic responses to energy intake and temperature but also by differences in minor activity. Interactions between activity and environmental factors such as nutrition and temperature can modify the effect of activity on energy balance. Very little is known about mechanisms that could account for differences in spontaneous activity and these need to be the subject of future investigations.     

An energy 'sources' and 'fractions' approach to the mechanical energy expenditure problem--V. The mechanical energy expenditure reduction during motion of the multi-link system

Mechanical energy economy during motion of the multi-link system is analyzed on the basis of the theory developed in the previous publications (parts I-IV of this series, J. Biomechanics 19, 287-309). The compensation coefficients for the F- and M-sources and also the absolute compensation coefficient reflecting the mechanical energy economy due to four possible resources are introduced. These resources are the antiphase fluctuations of (I) each link's total energy fractions involving energy transformations between (1) rotational and translational fractions by F-sources, (2) kinetic and potential fractions by mg-source; (II) the links' total energies involving energy transfers between (3) links by F-sources, (4) links by M-sources. The conditions of mechanical energy economy, particularly due to M-sources, are analyzed.     

Inhibiting influence of testosterone on stress responsiveness during adolescence

The maturation of the hypothalamo-pituitary-adrenal (HPA) axis is a key-component of the changes that occur during adolescence. In guinea pigs, HPA responsiveness during late adolescence depends strongly on the quantity and quality of social interactions: Males that lived in a large mixed-sex colony over the course of adolescence exhibit a lower stress response than males that were kept in pairs (one male/one female). Since colony-housed males have higher testosterone (T) levels than pair-housed males, and inhibiting effects of T on HPA function are well known, we tested the hypothesis that the decrease in stress responsiveness found in colony-housed males is due to their high T concentrations. We manipulated T levels in two experiments: 1) gonadectomy/sham-gonadectomy of colony-housed males (which usually have high T levels), 2) application of T undecanoate/vehicle to pair-housed males (which usually have low T levels). As expected, gonadectomized males showed a significantly increased stress response in comparison with sham-gonadectomized males, and T-injected males had a significantly lower stress response than vehicle-injected males. Both experiments thus confirm an inhibiting effect of T on HPA responsiveness during adolescence, which can mediate the influence of social interactions. The reduction in stress responsiveness is hypothesized to have a biologically adaptive value: A sudden increase in glucocorticoid concentrations can enhance aggressive behavior. Thus, pair-housed males might be adapted to aggressively defend their female (‘resource defense strategy’), whereas colony-housed males display little aggressive behavior and are capable of integrating themselves into a colony (‘queuing strategy’).     

Anaerobic energy expenditure and mechanical efficiency during exhaustive leg press exercise

Information about anaerobic energy production and mechanical efficiency that occurs over time during short-lasting maximal exercise is scarce and controversial. Bilateral leg press is an interesting muscle contraction model to estimate anaerobic energy production and mechanical efficiency during maximal exercise because it largely differs from the models used until now. This study examined the changes in muscle metabolite concentration and power output production during the first and the second half of a set of 10 repetitions to failure (10RM) of bilateral leg press exercise. On two separate days, muscle biopsies were obtained from vastus lateralis prior and immediately after a set of 5 or a set of 10 repetitions. During the second set of 5 repetitions, mean power production decreased by 19% and the average ATP utilisation accounted for by phosphagen decreased from 54% to 19%, whereas ATP utilisation from anaerobic glycolysis increased from 46 to 81%. Changes in contraction time and power output were correlated to the changes in muscle Phosphocreatine (PCr; r = −0.76; P<0.01) and lactate (r = −0.91; P<0.01), respectively, and were accompanied by parallel decreases (P<0.01-0.05) in muscle energy charge (0.6%), muscle ATP/ADP (8%) and ATP/AMP (19%) ratios, as well as by increases in ADP content (7%). The estimated average rate of ATP utilisation from anaerobic sources during the final 5 repetitions fell to 83% whereas total anaerobic ATP production increased by 9% due to a 30% longer average duration of exercise (18.4±4.0 vs 14.2±2.1 s). These data indicate that during a set of 10RM of bilateral leg press exercise there is a decrease in power output which is associated with a decrease in the contribution of PCr and/or an increase in muscle lactate. The higher energy cost per repetition during the second 5 repetitions is suggestive of decreased mechanical efficiency.     

Radiant heat affects thermoregulation and energy expenditure during rewarming from torpor

The high expenditure of energy required for endogenous rewarming is one of the widely perceived disadvantages of torpor. However, recent evidence demonstrates that passive rewarming either by the increase of ambient temperature or by basking in the sun appears to be common in heterothermic birds and mammals. As it is presently unknown how radiant heat affects energy expenditure during rewarming from torpor and little is known about how it affects normothermic thermoregulation, we quantified the effects of radiant heat on body temperature and metabolic rate of the small (body mass 25 g) marsupial Sminthopsis macroura in the laboratory. Normothermic resting individuals exposed to radiant heat were able to maintain metabolic rates near basal levels (at 0.91 ml O(2) g(-1) h(-1)) and a constant body temperature down to an ambient temperature of 12 degrees C. In contrast, metabolic rates of individuals without access to radiant heat were 4.5-times higher at an ambient temperature of 12 degrees C and body temperature fell with ambient temperature. During radiant heat-assisted passive rewarming from torpor, animals did not employ shivering but appeared to maximise uptake of radiant heat. Their metabolic rate increased only 3.2-times with a 15- degrees C rise of body temperature (Q(10)=2.2), as predicted by Q(10) effects. In contrast, during active rewarming shivering was intensive and metabolic rates showed an 11.6-times increase. Although body temperature showed a similar absolute change between the beginning and the end of the rewarming process, the overall energetic cost during active rewarming was 6.3-times greater than that during passive, radiant heat-assisted rewarming. Our study demonstrates that energetic models assuming active rewarming from torpor at low ambient temperatures can substantially over-estimate energetic costs. The low energy expenditure during passive arousal provides an alternative explanation as to why daily torpor is common in sunny regions and suggests that the prevalence of torpor in low latitudes may have been under-estimated in the past.