Unaltered glucose-induced thermogenesis in Graves' disease.

The thermogenic response to a 100-g oral glucose challenge was studied in 12 patients with Graves' disease using continuous indirect calorimetry. Seven hyperthyroid patients were reinvestigated under the same experimental conditions after medical therapy. The mean net increase in energy expenditure (delta EE) following the glucose challenge was the same in hyperthyroid patients as compared to a control group (delta EE = +0.15 +/- 0.02 and 0.15 +/- 0.01 kcal/min, respectively) and the treated patients (delta EE = +0.11 +/- 0.03 kcal/min ns). When expressed as a percentage of the energy content of the glucose challenge, the mean glucose induced thermogenesis was similar in all three groups: 7.0 +/- 1.0%, 7.4 +/- 0.5%, and 5.5 +/- 1.3% in hyperthyroid, control subjects, and treated patients, respectively. It is concluded that the high energy requirement of hyperthyroid patients is due primarily to an elevated resting energy expenditure. The postprandial thermogenesis in itself does not contribute to the elevated fuel utilization in Graves' disease.

Nutritional influences on lipogenesis and thermogenesis after a carbohydrate meal.

In vivo lipogenesis and thermogenesis were studied for 24 h after ingestion of 500 g of carbohydrate (CHO) in subjects who had consumed either a high-fat, a mixed, or a high-CHO diet during the 3-6 days preceding the test. CHO oxidation and conversion to fat was significantly less in the high-fat diet group (222 +/- 5 g) than in the mixed (300 +/- 13 g) or high-CHO diet (331 +/- 7 g) groups, resulting in a greater glycogen storage in the high-fat (278 +/- 6 g) than in the other two groups (197 +/- 11 and 170 +/- 2 g). Net lipogenesis occurred sooner and lasted longer in the high-CHO group, amounting to 0.8 +/- 0.5, 3.4 +/- 0.6, and 9 +/- 1 g of lipid synthesized in the high-fat, mixed, and high-CHO groups, respectively. The thermic effect of the CHO load was 5.2 +/- 0.5% on the high-fat, 6.5 +/- 0.4% on the mixed diet, and 8.6 +/- 0.4% on the high-CHO diet. Significant relationships were demonstrated between the postabsorptive nonprotein respiratory quotient and net lipogenesis after the CHO load (r = 0.82) and between net lipogenesis and the increase in energy expenditure (r = 0.71). It is concluded that the antecedent diet influences the amount of net lipogenesis and the magnitude of thermogenesis after a large CHO test meal. However, lipogenesis remains too limited even after such large CHO intakes to cause an increase in the body's fat content.

Diurnal and exercise-related variability of haemoglobin and reticulocytes in athletes.

Haemoglobin (Hb) and Reticulocytes (Ret) are measured as indirect markers of doping in athletes. We studied the diurnal variation, the impact of exercise, fluid intake and ambient temperature in athletes on these parameters. Hourly venous blood samples were obtained from 36 male athletes of different disciplines (endurance (END) and non-endurance (NON-END)) over 12 h during a typical training day. Seven inactive subjects served as controls (CON). Hb and Ret were determined. A mixed model procedure was used to analyse the data. At baseline, Hb was similar for all groups, END showed lower Ret than NON-END and CON. Exercise showed a significant impact on Hb (+0.46 g/dl, p<0.001), the effect disappeared approximately 2 h after exercise. Hb decreased over the day by approximately 0.55 g/dl (p<0.01). There was no relevant effect on Ret. Fluid intake and ambient temperature had no significant effect. Hb shows significant diurnal- and exercise related variations. In an anti-doping context, most of these variations are in favour of the athlete. Blood samples taken after exercise might therefore provide reliable results and thus be used for the longitudinal monitoring of athletes if a timeframe for the re-equilibration of vascular volumes is respected.

Postprandial thermogenesis in lactating and non-lactating women from The Gambia.

Postprandial thermogenesis was assessed by indirect calorimetry in 32 Gambian women classified into three groups as follows: 12 non-pregnant non-lactating and 10 lactating women studied during the dry season and 10 lactating women studied during the rainy season. The test meal consisted of a typical Gambian breakfast and its energy content corresponded to 30% of the individual's resting metabolic rate (RMR)/24 h. During the dry season, the postprandial thermogenesis of the lactating women averaged 6.0 +/- 0.4% of the test meal energy content and was similar to that observed in the non-pregnant non-lactating women studied during the same season (5.8 +/- 0.3%). In contrast, the postprandial thermogenesis of lactating women studied during the rainy, nutritionally unfavourable season was found to be significantly lower (4.9 +/- 0.5%). There was no significant difference in the pre- and postprandial respiratory quotients among groups. This leads to the conclusion that lactation does not alter the thermogenic response to food and that the reduction in postprandial thermogenesis observed in lactating women during the wet season constitutes an adaptive response to energy deficit allowing a saving of energy in periods of food restriction.

Glut2-dependent glucose-sensing controls thermoregulation by enhancing the leptin sensitivity of NPY and POMC neurons.

The physiological contribution of glucose in thermoregulation is not completely established nor whether this control may involve a regulation of the melanocortin pathway. Here, we assessed thermoregulation and leptin sensitivity of hypothalamic arcuate neurons in mice with inactivation of glucose transporter type 2 (Glut2)-dependent glucose sensing. Mice with inactivation of Glut2-dependent glucose sensors are cold intolerant and show increased susceptibility to food deprivation-induced torpor and abnormal hypothermic response to intracerebroventricular administration of 2-deoxy-d-glucose compared to control mice. This is associated with a defect in regulated expression of brown adipose tissue uncoupling protein I and iodothyronine deiodinase II and with a decreased leptin sensitivity of neuropeptide Y (NPY) and proopiomelanocortin (POMC) neurons, as observed during the unfed-to-refed transition or following i.p. leptin injection. Sites of central Glut-2 expression were identified by a genetic tagging approach and revealed that glucose-sensitive neurons were present in the lateral hypothalamus, the dorsal vagal complex, and the basal medulla but not in the arcuate nucleus. NPY and POMC neurons were, however, connected to nerve terminals from Glut2-expressing neurons. Thus, our data suggest that glucose controls thermoregulation and the leptin sensitivity of NPY and POMC neurons through activation of Glut2-dependent glucose-sensing neurons located outside of the arcuate nucleus.

Comparison of thermogenic effect of fructose and glucose in normal humans.

After nutrient ingestion there is an increase in energy expenditure that has been referred to as dietary-induced thermogenesis. In the present study we have employed indirect calorimetry to compare the increment in energy expenditure after the ingestion of 75 g of glucose or fructose in 17 healthy volunteers. During the 4 h after glucose ingestion the plasma insulin concentration increased by 33 +/- 4 microU/ml and this was associated with a significant increase in carbohydrate oxidation and decrement in lipid oxidation. Energy expenditure increased by 0.08 +/- 0.01 kcal/min. When fructose was ingested, the plasma insulin concentration increased by only 8 +/- 2 microU/ml vs. glucose. Nonetheless, the increments in carbohydrate oxidation and decrement in lipid oxidation were significantly greater than with glucose. The increment in energy expenditure was also greater with fructose. When the mean increment in plasma insulin concentration after fructose was reproduced using the insulin clamp technique, the increase in carbohydrate oxidation and decrement in lipid oxidation were markedly reduced compared with the fructose-ingestion study; energy expenditure failed to increase above basal levels. To examine the role of the adrenergic nervous system in fructose-induced thermogenesis, fructose ingestion was also performed during beta-adrenergic blockade with propranolol. The increase in energy expenditure during fructose plus propranolol was lower than with fructose ingestion alone. These results indicate that the stimulation of thermogenesis after carbohydrate ingestion is related to an augmentation of cellular metabolism and is not dependent on an increase in the plasma insulin concentration per se.(ABSTRACT TRUNCATED AT 250 WORDS)

Beta-adrenergic blockade and intravenous nutrient-induced thermogenesis in lean and obese women.

Continuous respiratory exchange measurements were performed in nine obese and eight lean women for 1 h before, 3 h during, and 1 h after the intravenous administration of a nutrient mixture infused at twice the postabsorptive resting energy expenditure (REE). This experiment was conducted without or with beta-adrenergic blockade (iv propranolol). Propranolol administration did not change the postabsorptive REE [i.e., 1.03 +/- 0.07 before vs. 1.01 +/- 0.02 kcal/min after administration in lean women and 1.16 +/- 0.04 vs. 1.15 +/- 0.03 kcal/min (NS) in obese women]. The mean overall thermogenic response expressed as a percentage of the infused energy was similar in both groups and was not significantly blunted after propranolol infusion [6.9 +/- 0.4 vs. 5.9 +/- 0.6% in the lean women and 7.5 +/- 0.5 vs. 7.1 +/- 0.6% (NS) in the obese women]. During beta-adrenergic blockade the rate of lipid oxidation decreased in the lean group but was unchanged in the obese group and the glycemic response to nutrient administration was significantly higher in both groups than without propranolol. It is concluded that beta-adrenergic blockade has no effect on REE and on intravenous nutrient-induced thermogenesis in both lean and obese women.

Decreased thermal conductance during the luteal phase of the menstrual cycle in women.

To study the influence of the menstrual cycle on whole body thermal balance and on thermoregulatory mechanisms, metabolic heat production (M) was measured by indirect calorimetry and total heat losses (H) were measured by direct calorimetry in nine women during the follicular (F) and the luteal (L) phases of the menstrual cycle. The subjects were studied while exposed for 90 min to neutral environmental conditions (ambient temperature 28 degrees C, relative humidity 40%) in a direct calorimeter. The values of M and H were not modified by the phase of the menstrual cycle. Furthermore, in both phases the subjects were in thermal equilibrium because M was similar to H (69.7 +/- 1.8 and 72.1 +/- 1.8 W in F and 70.4 +/- 1.9 and 71.4 +/- 1.7 W in L phases, respectively). Tympanic temperature (Tty) was 0.24 +/- 0.07 degrees C higher in the L than in the F phase (P less than 0.05), whereas mean skin temperature (Tsk) was unchanged. Calculated skin thermal conductance (Ksk) was lower in the L (17.9 +/- 0.6 W.m-2.degrees C-1) than in the F phase (20.1 +/- 1.1 W.m-2.degrees C-1; P less than 0.05). Calculated skin blood flow (Fsk) was also lower in the L (0.101 +/- 0.008 l.min-1.m-2) than in the F phase (0.131 +/- 0.015 l.min-1.m-2; P less than 0.05). Differences in Tty, Ksk, and Fsk were not correlated with changes in plasma progesterone concentration. It is concluded that, during the L phase, a decreased thermal conductance in women exposed to a neutral environment allows the maintenance of a higher internal temperature.

Induced normothermia attenuates cerebral metabolic distress in patients with aneurysmal subarachnoid hemorrhage and refractory Fever.

BACKGROUND AND PURPOSE: The purpose of this study was to analyze whether fever control attenuates cerebral metabolic distress after aneurysmal subarachnoid hemorrhage (SAH). METHODS: Eighteen SAH patients, who underwent intracranial pressure (ICP) and cerebral microdialysis monitoring and were treated with induced normothermia for refractory fever (body temperature >or=38.3 degrees C, despite antipyretics), were studied. Levels of microdialysate lactate/pyruvate ratio (LPR) and episodes of cerebral metabolic crisis (LPR >40) were analyzed during fever and induced normothermia, at normal and high ICP (>20 mm Hg). RESULTS: Compared to fever, induced normothermia resulted in lower LPR (40+/-24 versus 32+/-9, P<0.01) and a reduced incidence of cerebral metabolic crisis (13% versus 5%, P<0.05) at normal ICP. During episodes of high ICP, induced normothermia was associated with a similar reduction of LPR, fewer episodes of cerebral metabolic crisis (37% versus 8%, P<0.01), and lower ICP (32+/-11 versus 28+/-12 mm Hg, P<0.05). CONCLUSIONS: Fever control is associated with reduced cerebral metabolic distress in patients with SAH, irrespective of ICP.

Thermogenesis in obese women: effect of fructose vs. glucose added to a meal.

To assess the effect of a fructose meal on resting energy expenditure (EE), indirect calorimetry was used in 23 women (10 lean and 13 obese) for 30 min before and 6 h after the ingestion of a mixed meal containing 20% protein, 33% fat, and either 75 g glucose or 75 g fructose as carbohydrate source (47%). Expressed as a percentage of the energy content of the meal, the thermogenic response to the fructose meal was significantly greater (10.2 +/- 0.5%) than that of the glucose meal (8.4 +/- 0.4%, P less than 0.01). This difference was still apparent when the lean and obese women were considered separately. The mean respiratory quotient during the 6-h postprandial period was significantly greater (P less than 0.01) for the fructose (0.85 +/- 0.01) than for the glucose meal (0.83 +/- 0.01) in the combined subjects. In addition, cumulative carbohydrate oxidation was significantly greater after the fructose than after the glucose meal (51.1 +/- 2.3 vs. 40.9 +/- 2.0 g/6 h, respectively, P less than 0.01). Only small changes were observed in postprandial plasma levels of glucose and insulin after the fructose meal, but the plasma levels of lactate increased more with fructose than with the glucose meal. These results suggest that there might be some advantages (higher thermogenesis and carbohydrate oxidations) in using fructose as part of the carbohydrate source in diet of people with obesity and/or insulin resistance.

Investigations of a thermosensitive gel to temporarily occlude crural arteries in femoro-distal bypass surgery.

OBJECTIVES: Long occlusions in calcified crural arteries are a major cause of endovascular technical failure in patients with critical limb ischaemia. Therefore, distal bypasses are mainly performed in patients with heavily calcified arteries and with consequently delicate clamping. A new reverse thermosensitive polymer (RTP) is an alternative option to occlude target vessels. The aim of the study is to report our technical experience with RTP and to assess its safety and efficiency to temporarily occlude small calcified arteries during anastomosis time. METHODS: Between July 2010 and December 2011, we used RTP to occlude crural arteries in 20 consecutive patients with 20 venous distal bypasses. We recorded several operative parameters, such as volume of injected RTP, duration of occlusion and anastomotic time. Quality of occlusion was subjectively evaluated. Routine on-table angiography was performed to search for plug emboli. Primary patency, limb salvage and survival rates were reported at 6 months. RESULTS: In all patients, crural artery occlusion was achieved with the RTP without the use of an adjunct occlusion device. Mean volume of RTP used was 0.3 ml proximally and 0.25 ml distally. Mean duration of occlusion was 14.4 ± 4.5 min, while completion of the distal anastomosis lasted 13.4 ± 4.3 min. Quality of occlusion was judged as excellent in eight cases and good in 12 cases. Residual plugs were observed in two patients and removed with an embolectomy catheter, before we amended the technique for dissolution of RTP. At 6 months, primary patency rate was 75% but limb salvage rate was 87.5%. The 30-day mortality rate was 10%. CONCLUSIONS: This study shows that RTP is safe when properly dissolved and effective to occlude small calcified arteries for completion of distal anastomosis.

Primary fluid bolus therapy for infection-associated hypotension in the emergency department.

OBJECTIVES: The physiological changes associated with fluid bolus therapy (FBT) for patients with infection-associated hypotension in the emergency department (ED) are poorly understood. We describe the physiological outcomes of FBT in the first 6 hours (primary FBT) for patients presenting to the ED with infection-associated hypotension. METHODS: We studied 101 consecutive ED patients with infection and a systolic blood pressure (SBP)<100 mmHg who underwent FBT in the first 6 hours. RESULTS: We screened 1123 patients with infection and identified 101 eligible patients. The median primary FBT volume given was 1570 mL (interquartile range, 1000- 2490 mL). The average mean arterial pressure (MAP) did not change from admission to 6 hours in the whole cohort, or in patients who were hypotensive on arrival at the ED. However, the average MAP increased from its lowest value during the first 6 hours (66 mmHg [SD, 10 mmHg]) to its value at 6 hours (73 mmHg [SD, 12 mmHg]; P<0.001). The mean heart rate, body temperature, respiratory rate and plasma creatinine level decreased (P<0.05). In patients who were severely hypotensive (SBP<90 mmHg) on arrival at the ED, the MAP increased from 54 mmHg (SD, 8 mmHg) to 70 mmHg (SD, 14 mmHg) (P<0.001). At 6 hours, however, SBP was still <100 mmHg in 44 patients and <90 mmHg in 17 patients. When noradrenaline was used, in 10 patients, hypotension was corrected in all 10 and the MAP increased from 58 mmHg (SD, 9 mmHg) to 75 mmHg (SD, 13 mmHg). CONCLUSION: Among ED patients admitted to an Australian teaching hospital with infection, hypotension was uncommon. FBT for hypotension was limited in volumes given and failed to achieve a sustained SBP of >100 mmHg in 40% of cases. In contrast, noradrenaline therapy corrected hypotension in all patients who received it.

Thermogenic effect of the new beta-adrenoreceptor agonist Ro 16-8714 in healthy male volunteers.

Previous investigations in experimental animals have shown that a new type of beta-adrenoceptor agonist (Ro 16-8714) possesses both thermogenic and antihyperglycemic properties. The aim of the study was to assess the thermogenic capacity of the compound in man after acute administration. Following an overnight fast three different doses (5, 10 and 20 mg) and a placebo were given per os to six normal-weight young men. The rate of energy expenditure (EE) and substrate utilization were determined by indirect calorimetry (hood system) before and for 6 h following the drug administration. Heart rate and blood pressure as well as plasma glucose, insulin and free fatty acid (FFA) concentrations were also measured at regular intervals throughout the study. The increment relative to base-line (mean +/- s.e.m.) in EE with placebo, 5, 10 and 20 mg was 4 +/- 3, 10 +/- 2, 11 +/- 2 and 21 +/- 2 percent respectively whereas heart rate was enhanced by 2 +/- 2, 8 +/- 3, 22 +/- 2, and 49 +/- 8 percent. Systolic blood pressure increased less (1 +/- 2, 8 +/- 1, 11 +/- 1 and 13 +/- 2 percent), and diastolic blood pressure did not change significantly. Simultaneously we observed a slight and transient increase in blood glucose, insulin and FFA concentrations. It is concluded that in lean individuals Ro 16-8714 is a potent thermogenic agent; however, new beta-adrenoceptor agonists should be developed in order to avoid the tachycardia associated with the thermogenic effect.

Diving capacity and foraging behaviour of the water shrew (Neomys fodiens)

With regard to semi-aquatic mammals, Schröpfer & Stubbe (1992) distinguished three riparian guilds: the herbivores with the water vole and the beaver; the megacarnivores with the mink and the otter; and the macrocarnivores with water shrews and desmans. Among water shrews, the evolution of aquatic foraging behaviour occurred several times: Nectogale and Chimarrogale in Asia, several species of the genus Sorex in America, and Neomys in Eurasia (Churchfield, 1990). The fairly common European water shrew N. fodiens is the best known. However, the reports on the degree of adaptation to the water habitat are conflicting. Therefore some important findings from the literature are reviewed in this introduction, whereas new data are presented in the following sections. The swimming locomotion of water shrews was analysed by Ruthardt & Schröpfer (1985) and Köhler (1991), and the related morphological adaptation were reviewed by Hutterer (1985) and Churchfield (this volume pp. 49-51). They obviously present a compromise between the requirements for activity on land and in the water. Thermoregulation is a major problem for semi-aquatic mammals, because heat conductance in water is 25-fold greater than in air (Calder, 1969). According to this author, the body temperature of immersed American Sorex palustris dropped by a rate of 2.8 °C per min. However, this may be an experimental artefact, because Neomys fodiens can maintain its body temperature at 37 °C during an immersion of 6 min (Vogel, 1990).

The systemic control of circadian gene expression.

The mammalian circadian timing system consists of a central pacemaker in the brain's suprachiasmatic nucleus (SCN) and subsidiary oscillators in nearly all body cells. The SCN clock, which is adjusted to geophysical time by the photoperiod, synchronizes peripheral clocks through a wide variety of systemic cues. The latter include signals depending on feeding cycles, glucocorticoid hormones, rhythmic blood-borne signals eliciting daily changes in actin dynamics and serum response factor (SRF) activity, and sensors of body temperature rhythms, such as heat shock transcription factors and the cold-inducible RNA-binding protein CIRP. To study these systemic signalling pathways, we designed and engineered a novel, highly photosensitive apparatus, dubbed RT-Biolumicorder. This device enables us to record circadian luciferase reporter gene expression in the liver and other organs of freely moving mice over months in real time. Owing to the multitude of systemic signalling pathway involved in the phase resetting of peripheral clocks the disruption of any particular one has only minor effects on the steady state phase of circadian gene expression in organs such as the liver. Nonetheless, the implication of specific pathways in the synchronization of clock gene expression can readily be assessed by monitoring the phase-shifting kinetics using the RT-Biolumicorder.