Starvation-induced decreased sensitivity of resting metabolic rate to triiodothyronine.

The decrease in resting oxygen consumption induced by starvation was found to occur not only in euthyroid rats but also in hypothyroid and even in hypothyroid animals treated with triiodothyronine. Furthermore, the effectiveness of triiodothyronine was decreased when given to hypothyroid animals.

Household decision-making about delivery in health facilities: evidence from Tanzania.

This study investigated how partners' perceptions of the healthcare system influence decisions about delivery-location in low-resource settings. A multistage population-representative sample was used in Kasulu district, Tanzania, to identify women who had given birth in the last five years and their partners. Of 826 couples in analysis, 506 (61.3%) of the women delivered in the home. In multivariate analysis, factors associated with delivery in a health facility were agreement of partners on the importance of delivering in a health facility and agreement that skills of doctors are better than those of traditional birth attendants. When partners disagreed, the opinion of the woman was more influential in determining delivery-location. Agreement of partners regarding perceptions about the healthcare system appeared to be an important driver of decisions about delivery-location. These findings suggest that both partners should be included in the decision-making process regarding delivery to raise rates of delivery at facility.

Evidence that insulin resistance is responsible for the decreased thermic effect of glucose in human obesity.

The thermic effect of glucose was investigated in nine obese and six lean subjects in whom the same rate of glucose uptake was imposed. Continuous indirect calorimetry was performed for 240 min on the supine subject. After 45 min, 20% glucose was infused (609 mg/min) for 195 min and normoglycemia was maintained by adjusting the insulin infusion rate. At 2 h, propranolol was infused (bolus 100 micrograms/kg; 1 microgram/kg X min) for the remaining 75 min. To maintain the same glucose uptake (0.624 g/min), it was necessary to infuse insulin at 3.0 +/- 0.6 (leans) and 6.6 +/- 1.2 mU/kg X min (obese) (P less than 0.02). At this time, glucose oxidation was 0.248 +/- 0.019 (leans) and 0.253 +/- 0.022 g/min (obese) (NS), and nonoxidative glucose disposal was 0.375 +/- 0.011 and 0.372 +/- 0.029 g/min, respectively. Resting metabolic rate (RMR) rose significantly by 0.13 +/- 0.02 kcal/min in both groups, resulting in similar thermic effects, i.e., 5.5 +/- 0.7% (leans) 5.4 +/- 0.9% (obese) (NS) and energy costs of glucose storage 0.35 +/- 0.06 and 0.39 +/- 0.09 kcal/g (NS), respectively. With propranolol, glucose uptake and storage remained the same, while RMR fell significantly in both groups, with corresponding decreases (P less than 0.05) in the thermic effects of glucose to 3.7 +/- 0.6% and 2.9 +/- 0.8% (NS) and the energy costs of glucose storage 0.23 +/- 0.04 and 0.17 +/- 0.05 kcal/g (NS) in the lean and obese subjects, respectively. These results suggest that the defect in the thermic effect of glucose observed in obese subjects is due to their insulin resistance, which is responsible for a lower rate of glucose uptake and hence decreased rate of glucose storage, which is an energy-requiring process.

Capacity for moderate exercise in obese subjects after adaptation to a hypocaloric, ketogenic diet.

To study the capacity for moderate endurance exercise and change in metabolic fuel utilization during adaptation to a ketogenic diet, six moderately obese, untrained subjects were fed a eucaloric, balanced diet (base line) for 2 wk, followed by 6 wk of a protein-supplemented fast (PSF), which provided 1.2 g of protein/kg ideal body wt, supplemented with minerals and vitamins. The mean weight loss was 10.6 kg. The duration of treadmill exercise to subjective exhaustion was 80% of base line after 1 wk of the PSF, but increased to 155% after 6 wk. Despite adjusting up to base line, with a backpack, the subjects' exercise weight after 6 wk of dieting, the final exercise test was performed at a mean of 60% of maximum aerobic capacity, whereas the base-line level was 76%. Resting vastus lateralis glycogen content fell to 57% of base line after 1 wk of the PSF, but rose to 69% after 6 wk, at which time no decrement in muscle glycogen was measured after >4 h of uphill walking. The respiratory quotient (RQ) during steady-state exercise was 0.76 during base line, and fell progressively to 0.66 after 6 wk of the PSF. Blood glucose was well maintained during exercise in ketosis. The sum of acetoacetate and beta hydroxybutyrate rose from 3.28 to 5.03 mM during exercise after 6 wk of the PSF, explaining in part the low exercise RQ. The low RQ and the fact that blood glucose and muscle glycogen were maintained during exhausting exercise after 6 wk of a PSF suggest that prolonged ketosis results in an adaptation, after which lipid becomes the major metabolic fuel, and net carbohydrate utilization is markedly reduced during moderate but ultimately exhausting exercise.

Glucose metabolism and the response to insulin by human adipose tissue in spontaneous and experimental obesity. Effects of dietary composition and adipose cell size.

[1-(14)C]glucose oxidation to CO(2) and conversion into glyceride by adipose tissue from nonobese and obese subjects has been studied in vitro in the presence of varying medium glucose and insulin concentrations as functions of adipose cell size, the composition of the diet, and antecedent weight gain or loss. Increasing medium glucose concentrations enhance the incorporation of glucose carbons by human adipose tissue into CO(2) and glyceride-glycerol. Insulin further stimulates the conversion of glucose carbons into CO(2), but not into glyceride-glycerol. Incorporation of [1-(14)C]glucose into glyceride-fatty acids by these tissues could not be demonstrated under any of the conditions tested. Both adipose cell size and dietary composition influence the in vitro metabolism of glucose in, and the response to insulin by, human adipose tissue. During periods of ingestion of weight-maintenance isocaloric diets of similar carbohydrate, fat, and protein composition, increasing adipose cell size is associated with (a) unchanging rates of glucose oxidation and increasing rates of glucose carbon incorporation into glyceride-glycerol in the absence of insulin, but (b) decreasing stimulation of glucose oxidation by insulin. On the other hand, when cell size is kept constant, increasing dietary carbohydrate intake is associated with an increased basal rate of glucose metabolism and response to insulin by both small and large adipose cells. Thus, the rate of glucose oxidation and the magnitude of the insulin response of large adipose cells from individuals ingesting a high carbohydrate diet may be similar to or greater than that in smaller cells from individuals ingesting an isocaloric lower carbohydrate diet.The alterations in basal glucose metabolism and insulin response observed in adipose tissue from patients with spontaneous obesity are reproduced by weight gain induced experimentally in nonobese volunteers; these metabolic changes are reversible with weight loss. The relationships among adipose cell size, dietary composition, and the metabolism of adipose tissue are similar in spontaneous and in experimental obesity.

Dietary-induced alterations in thyroid hormone metabolism during overnutrition.

Diet-induced alterations in thyroid hormone concentrations have been found in studies of long-term (7 mo) overfeeding in man (the Vermont Study). In these studies of weight gain in normal weight volunteers, increased calories were required to maintain weight after gain over and above that predicted from their increased size. This was associated with increased concentrations of triiodothyronine (T3). No change in the caloric requirement to maintain weight or concentrations of T3 was found after long-term (3 mo) fat overfeeding. In studies of short-term overfeeding (3 wk) the serum concentrations of T3 and its metabolic clearance were increased, resulting in a marked increase in the production rate of T3 irrespective of the composition of the diet overfed (carbohydrate 29.6 +/- 2.1 to 54.0 +/- 3.3, fat 28.2 +/- 3.7 to 49.1 +/- 3.4, and protein 31.2 +/- 2.1 to 53.2 +/- 3.7 microgram/d per 70 kg). Thyroxine production was unaltered by overfeeding (93.7 +/- 6.5 vs. 89.2 +/- 4.9 microgram/d per 70 kg). It is still speculative whether these dietary-induced alterations in thyroid hormone metabolism are responsible for the simultaneously increased expenditure of energy in these subjects and therefore might represent an important physiological adaptation in times of caloric affluence. During the weight-maintenance phases of the long-term overfeeding studies, concentrations of T3 were increased when carbohydrate was isocalorically substituted for fat in the diet. In short-term studies the peripheral concentrations of T3 and reverse T3 found during fasting were mimicked in direction, if not in degree, with equal or hypocaloric diets restricted in carbohydrate were fed. It is apparent from these studies that the caloric content as well as the composition of the diet, specifically, the carbohydrate content, can be important factors in regulating the peripheral metabolism of thyroid hormones.

Thermic effect of infused glucose and insulin in man. Decreased response with increased insulin resistance in obesity and noninsulin-dependent diabetes mellitus.

The thermic effect of infused glucose and insulin was measured by combining the hyperinsulinemic euglycemic clamp technique with indirect calorimetry, in 10 normal weight volunteers (group I), 7 obese subjects with normal glucose tolerance (group II), and 13 obese subjects with abnormal glucose tolerance or noninsulin-dependent diabetes mellitus before (group IIIa) and after weight loss of 10.8 +/- 0.4 kg (group IIIb). During hyperinsulinemia (760-1,100 pmol/liter), total glucose disposal from combined endogenous production and glucose infusion was 545 +/- 49, 441 +/- 70, 233 +/- 35, 231 +/- 31 mg/min and energy expenditure changed by + 0.476 +/- 0.080, +0.293 +/- 0.095, -0.114 +/- 0.063, and +0.135 +/- 0.082 kJ/min in group I, II, IIIa, and IIIb, respectively. The increased energy expenditure correlated with glucose storage (measured cost of processing the glucose: 1.33 kJ/g). In group IIIa there was no increase in energy expenditure in response to glucose and insulin infusions. After therapy (group IIIb) there was a significant recovery (P less than 0.05) of the thermic effect of infused glucose although total glucose disposal was unchanged. It is proposed that the recovered thermic effect of infused insulin/glucose is due to the different contributions of gluconeogenesis in the fasting state and during the glucose clamp before and after weight loss. In addition we hypothesize that some of the lower thermic effect of food reported in obese noninsulin-dependent diabetics may be explained by decreased energy expenditure due to a greater suppression of hepatic gluconeogenesis as well as by lower storage rate.

Effects of chronic beta receptor stimulation on glucose metabolism.

The acute administration of a beta receptor-stimulating agent profoundly affects insulin-mediated glucose metabolism; however, little is known about the impact of chronic beta receptor stimulation on glucose metabolism and insulin sensitivity. We therefore investigated the effect of the chronic administration of a beta-2-agonist, terbutaline sulfate (TS), on glucose metabolism in 7 healthy, normal-weight, male volunteers between the ages of 21 and 30 yr. Studies were performed using the euglycemic, hyperinsulinemic (1.0 mU/min X kg) clamp technique before and after the oral administration of 5 mg of TS three times a day for 1 and 2 wk. Basal endogenous glucose production (EGP) (2.54 +/- 0.11 versus 2.64 +/- 0.14 mg/min X kg) and basal glucose oxidation (1.87 +/- 0.16 versus 2.0 +/- 0.2 mg/min X kg) were unchanged by the chronic administration of TS. However, insulin-stimulated total glucose metabolism increased by 29% (7.0 +/- 0.47 versus 9.05 +/- 0.67 mg/min X kg; P less than 0.02). Insulin-stimulated, nonoxidative glucose disposal increased by 45% (3.62 +/- 0.42 versus 5.26 +/- 0.48 mg/min X kg; P less than 0.01), while insulin-stimulated glucose oxidation did not change significantly (3.38 +/- 0.15 versus 3.79 +/- 0.22 mg/min X kg). EGP was completely suppressed under both conditions. Mean basal plasma insulin concentration (41 +/- 9 versus 49 +/- 15 pmol/L) and insulin clearance during the clamp procedure was unchanged (477 +/- 45 versus 474 +/- 37 ml/min X m2). We conclude that chronic beta receptor stimulation with TS improves insulin-stimulated glucose disposal in man, mostly by improving nonoxidative glucose disposal, i.e., "glucose storage."(ABSTRACT TRUNCATED AT 250 WORDS)

Increase in insulin action and fat oxidation after treatment with CL 316,243, a highly selective beta3-adrenoceptor agonist in humans.

Stimulation of beta3-adrenoceptors by selective agonists improves insulin action and stimulates energy metabolism in various rodent models of obesity and type 2 diabetes. Whether selective beta3-adrenoceptor stimulation exerts metabolic actions in humans remains to be proven. The effects of a highly selective beta3-adrenoceptor agonist on insulin action, energy metabolism, and body composition were assessed in 14 healthy young lean male volunteers (age 22.5 +/- 3.3 years, 15 +/- 5% body fat [mean +/- SD]) randomly assigned to 8 weeks of treatment with either 1,500 mg/day of CL 316,243 (n = 10) or placebo (n = 4). Insulin-mediated glucose disposal (IMGD), nonoxidative glucose disposal (NOGD), oxidative glucose disposal (OGD) (indirect calorimetry), and splanchnic glucose output (SGO; beta3-[H3]glucose) were determined during a 100-min hyperinsulinemic-euglycemic glucose clamp (40 mU x m(-2) x min(-1)) before and after 4 and 8 weeks of treatment. The 24-h energy expenditure (24-EE), 24-h respiratory quotient (24-RQ), and the oxidation rates of fat and carbohydrate were determined in a respiratory chamber before and after 8 weeks. After 4 weeks, treatment with CL 316,243 increased IMGD (+45%, P < 0.01) in a plasma concentration-dependent manner (r = 0.76, P < 0.02). This effect was due to an 82% increase in NOGD (P < 0.01), while OGD and SGO remained unchanged. The effects on insulin action were markedly diminished after 8 weeks; this was significantly related to an unexpected decline in the plasma concentrations of CL 316,243 (-36%, P = 0.08). At this time, 24-RQ was lowered (P < 0.001), corresponding to a 23% increase in fat oxidation (P < 0.01) and a 17% decrease in carbohydrate oxidation (P = 0.05). The 24-EE after 8 weeks did not differ from baseline, and there was no change in body weight or body composition. Plasma concentrations of glucose, insulin, and leptin were unaffected by treatment, while free fatty acid concentrations increased by 41% (P < 0.05), again linearly with the achieved plasma concentration of CL 316,243 (r = 0.67, P < 0.05). Treatment with CL 316,243 had no effect on heart rate or blood pressure and caused no cases of tremors. We conclude that treatment of lean male subjects with CL 316,243 increases insulin action and fat oxidation, both in a plasma concentration-dependent manner. This is the first study to demonstrate unequivocal metabolic effects of a highly selective beta3-adrenoceptor agonist in humans.

Seasonal variation and the influence of body temperature on plasma concentrations and binding of thyroxine and triiodothyronine in the woodchuck.

Woodchuck plasma was collected during four seasons of the year and assayed for total and dialyzable (free) T4 and T3 and for rT3. Plasma concentrations of total and free T4 and T3 were higher in the spring (T4, 5.4 +/- 0.6 microgram/dl; free T4, 3.0 +/- 0.4 ng/dl; T3, 202 +/- 22 ng/dl; free T3, 0.51 +/- 0.04 ng/dl) and lower in the prehibernatory fattening period in summer (T4, 2.3 +/- 1.0 microgram/dl; free T4, 1.2 +/- 0.5 ng/dl; T3, 45 +/- 27 ng/dl; free T3, 0.16 +/- 0.10 ng/dl) and fall (T4, 3.2 +/- 1.0 microgram/dl; free T4, 1.3 +/- 0.2 ng/dl; T3, 130 +/- 12 ng/dl; free T3, 0.25 +/- 0.02 ng/dl). In spite of the extremely high concentrations of T3 in the winter (437 +/- 32 ng/dl), free T3 concentrations (0.034 +/- 0.003 ng/dl), when measured at the appropriate temperature for hibernation, were significantly lower than those found at other seasons of the year. Plasma binding of T3 was lower during the summer and increased again to approximately double the spring value during the winter. rT3 was at or below the sensitivity of the method (6 ng/dl) at all seasons. It is suggested that the wide seasonal variations in thyroid hormone concentrations and altered plasma protein binding may represent important adaptations influencing the metabolic rate and the process of hibernation in the woodchuck.

Effects of chronic beta-receptor stimulation on sympathetic nervous system activity, energy expenditure, and thyroid hormones.

The effects of hyper- and hypothyroidism on sympathetic nervous system activity and energy expenditure are well recognized. The impact of altered sympathetic nervous system activity on energy expenditure and thyroid hormone metabolism has not been well studied. We investigated the effects of orally administered terbutaline sulfate, a beta 2-receptor agonist (5 mg, three times per day for 2 weeks), on the activity of the sympathetic nervous system, energy expenditure, and thyroid hormone metabolism in six normal men, aged 21-36 yr. The cardiovascular, metabolic, and thermogenic responses to an infusion of the beta-adrenergic agonist isoproterenol were clearly blunted after 2 weeks of treatment with terbutaline sulfate, indicating down-regulation of beta-receptors and/or development of reduced sensitivity. There were no significant changes in the cardiovascular, metabolic, or thermogenic responses to an infusion of the alpha-adrenergic agonist phenylephrine. Basal metabolic rate was significantly increased by the chronic administration of terbutaline sulfate [5.040 +/- 0.167 (+/- SE) vs. 5.421 +/- 0.234 kJ/min; P less than 0.05]. There was a highly significant change in the serum T3 to T4 ratio (19.4 +/- 1.0 vs. 24.4 +/- 1.0; P less than 0.001). This was a result of increased serum T3 concentrations (136 +/- 9 vs. 160 +/- 14 ng/dl; P less than 0.05) and decreased serum T4 concentrations (7.2 +/- 0.8 vs. 6.7 +/- 0.8 micrograms/dl; P = NS). Chronic beta-receptor stimulation with terbutaline sulfate increases the basal metabolic rate and T3 concentrations. These changes occurred despite down-regulation of beta-receptors and/or decreased sensitivity in response to chronic terbutaline administration.

Changes in serum concentrations of 3,3',5'-triiodothyronine and 3,5,3'-triiodothyronine during prolonged moderate exercise.

The effect of moderate bicycle exercise (3.5 h) on peripheral thyroid hormone metabolism was studied under two conditions (with and without glucose infusion) in four normal males. Serum T3, rT3, total protein, plasma glucose, and FFA were determined. Exercise induced an increase in rT3 from 29 to 40 ng/dl (P less than 0.01), a decrease in T3 from 154 to 147 ng/dl (P less than 0.01), and an increase in T4 from 7.1 to 7.5 micrograms/dl (P less than 0.05). When glucose was infused during exercise, the changes in rT3 were blunted (P less than 0.01) and the changes in T3 and T4 were diminished. During exercise, rT3 correlated with FFA (r = 0.95) and plasma glucose (r = -0.87). When glucose was infused during exercise, these correlations decreased (r = 0.81 and -0.56, respectively). Since moderate, prolonged exercise induces a state of early or acute starvation it is concluded that the changes in peripheral thyroid hormone metabolism reported here are similar to those found in starvation. The temporal changes of rT3, FFA, and plasma glucose during exercise suggest a relationship between thyroid hormone metabolism and the uptake and utilization of FFA and glucose or the mixture of these body fuels.

Monodeiodination of triiodothyronine and reverse triiodothyronine during low and high calorie diets.

The impact of varying caloric intake on peripheral monodeiodination and plasma disposal of T3, rT3, and the three diiodothyronines (T2) was studied in five normal subjects while they were consuming a low calorie diet (1200 Cal/day) and again while receiving a high calorie diet (3600 Cal/day). Toward the end of each diet period 240 nmol 3,3'-T2 (126 micrograms) and 80 nmol 3',5'-T2 (42 micrograms) were infused for 7 h, and a bolus injection of 137 nmol 3,5-T2 (72 micrograms) was followed by a 12-h infusion of 69 nmol 3,5-T2 (36 micrograms) and 111 nmol rT3 (72 micrograms) on another day. [125I]T3 (30 muCi) was injected on the third day. The T2 and rT3 concentrations were measured by RIA during the 2 days of infusion, and the serum disappearance of [125I]T3 was studied by immunoprecipitation and trichloroacetic acid precipitation of the labeled T3. Four to 5% of the plasma disposal of T3 was accounted for by 3'-monodeiodination, and 36-39% by 5-monodeiodination. Increasing caloric intake resulted in a higher overall plasma disposal rate of T3, but no change in the percentage of T3 metabolized by monodeiodination pathways. In contrast, 5'-monodeiodination accounted for 21% of the total plasma disposal of rT3 during the low calorie diet and 45% during the high calorie intake. This increase in 5'-monodeiodination of rT3 was at the expense of alternative pathways of disposal. A marked increase in the plasma clearance rate of 3,5-T2 was also found during the high calorie diet, indicating that the level of caloric intake affects pathways of metabolism other than outer ring monodeiodination. These studies emphasize the important role played by diet in the regulation of peripheral thyroid hormone metabolism through modulating outer ring monodeiodination, and that overnutrition changes other pathways of iodothyronine metabolism as well.

The interaction of free fatty acids in radioimmunoassays for reverse triiodothyronine.

We have investigated the effect of FFA on the RIA of rT3 because of our previous findings of a correlation between serum rT3 values and increased FFA concentrations during prolonged exercise and reports of interference by FFA in other thyroid hormone assays. Apparent rT3 values increased by 19% and 34% in in vivo studies of acute lipolysis in subjects 5 min post exercise or 10 min post heparin, respectively, while T3 and T4 concentrations were unchanged. Varying concentrations of palmitic acid were added in vitro to four normal sera, and the increase in FFA concentration correlated significantly with the increase in apparent rT3 values. The mean +/- SE of the regression slope was 9.3 +/- 1.8 ng/dl rT3/mM FFA (r = 0.96 +/- 0.02). The addition of linoleic acid produced a similar effect. T3 and T4 concentrations were unchanged. The interaction of FFA in the rT3 RIA was unrelated to the procedure used to separate the assay, to the concentration of 8-anilino-1-napthalene-sulfonic acid in the assay buffer, to FFA binding directly to the antisera or to use of a particular antisera. The magnitude of the effect was similar in charcoal-treated sera, and the addition of 2 mM palmitic acid to the assay standard curve decreased the y intercept but did not alter the slope, suggesting an interaction of rT3 with FFA, rather than change in affinity of the antisera.

The role of thyroid hormones and insulin in the regulation of energy metabolism.

Strong support has been gathered for a defect in insulin-glucose-mediated thermogenesis in obese and particularly obese insulin-resistant and/or diabetic subjects compared to lean subjects. This defect appears to be reversible with weight loss and improved insulin sensitivity. The mechanism for this blunted thermogic response is directly related to the decreased glucose storage in the obese and obese diabetic subjects.

Decreased thermic effect of a mixed meal during overnutrition in human obesity.

Short-term mixed calorie overfeeding increases basal energy expenditure in man but its effects on the thermic effect of a meal (TEM) are unclear. The thermogenic and hormonal responses to an 800-kcal liquid mixed meal were measured in six lean and six obese subjects during weight maintenance, during 18 d of overfeeding 1000 kcal/d, and during 18 d of a 589 kcal/d diet (obese subjects only). There was no change in the TEM in lean subjects between weight maintenance and overfeeding. In the obese group the TEM was lower during both overfeeding (p less than 0.05) and underfeeding (p less than 0.05) compared with weight maintenance. Overfeeding increased rates of net postprandial glucose oxidation and decreased lipid oxidation in the lean subjects only. Alterations in glucose oxidation rates and the insulin response to meals may contribute to an impaired TEM in human obesity during overnutrition.

Enteral versus parenteral nutrition: comparison of energy metabolism in lean and moderately obese women.

Continuous respiratory-exchange measurements were performed on ten moderately obese and ten lean young women for 1 h before, 3 h during, and 3 h after either parenteral (IV) or intragastric (IG) administration of a nutrient mixture infused at twice the postabsorptive, resting energy expenditure (REE). REE rose significantly from 0.98 +/- 0.02 to 1.13 +/- 0.03 kcal/min (IV) and from 0.99 +/- 0.02 to 1.13 +/- 0.02 kcal/min (IG) in the lean group; from 1.10 +/- 0.02 to 1.27 +/- 0.03 kcal/min (IV) and from 1.11 +/- 0.02 to 1.29 +/- 0.03 (IG) in the obese group. These increases resulted in similar nutrient-induced thermogenesis of 10.0 +/- 0.7% (IV) and 9.3 +/- 0.9% (IG) in the lean group; of 9.2 +/- 0.7% (IV) and 10.1 +/- 0.8% (IG) in the obese. Nutrient utilization was comparable in both groups and in both routes of administration, although the response time to IG feeding was delayed. These results showed no significant difference in both the thermogenic response and nutrient utilization between moderately obese and control groups using acute IV or IG feeding.

Thyroid hormones and thermogenesis: the metabolic cost of food and exercise.

To mimic plasma T3 levels observed in a previous overfeeding study, six lean healthy men received replacement amounts of L-thyroxine (200 micrograms/d) to block endogenous thyroid hormone production while consuming their habitual diet. After 4 weeks equilibration on T4, L-triiodothyronine (T3) was given (45 micrograms/d) in addition to T4, to produce mild T3-thyrotoxicosis, for another 2 weeks. At the end of this period T3 was discontinued but the subjects continued to receive T4 for another 2 weeks. Resting metabolic rate, exercise efficiency, and the thermic effect of food were measured using a ventilated hood, open circuit indirect calorimeter at the end of each phase of the experiment. There was a significant increase in the resting metabolic rate of 6% (P less than 0.01) while the subjects were mildly T3-thyrotoxic. The increase in energy expenditure however, during exercise on a bicycle ergometer or following a 500 kcal liquid-formula meal remained unaltered in the same situation. Thus, mild T3-toxicosis does not alter the efficiency of exercise or the thermic effect of food. These results suggest that the increased plasma T3 levels, observed in overfeeding, could explain corresponding increases in resting metabolic rate but not changes in the efficiency of exercise or the utilization of food.

Effects of aerobic exercise on energy expenditure and nitrogen balance during very low calorie dieting.

Aerobic exercise in addition to severe caloric restriction was studied for its effects on resting energy expenditure (REE), weight loss, and lean tissue preservation in adult women. A formula diet providing 1.5 g protein and 0.5 g carbohydrate (CHO) per kilogram of ideal body weight daily (mean intake 720 kcal/d) was given to 12 overweight inpatients for 4 to 5 weeks. Six subjects remained sedentary (group 1), while the other six subjects (group 2) performed supervised endurance exercise (a total of 27 hours at 50% of maximal oxygen uptake (VO2max) over 4 weeks). Lean tissue preservation was excellent in both groups and was unaffected by the group 2 exercise regimen. Weight loss over 4 weeks in the two groups did not differ (group 1, 6.9 +/- 0.7 kg; group 2, 6.5 +/- 0.7 kg). The VO2max was not increased after 4 weeks of exercise compared with controls. The resting oxygen consumption (rVO2) of both groups declined 10% (P less than .001) in the first seven days of dieting. Thereafter the rVO2 in group 1 remained stable, but a further 17% reduction occurred in group 2 (P less than .03) by the third week of exercise. The free triiodothyronine (fT3) concentration also fell more in group 2 (P less than .05), suggesting a relationship between fT3 and energy expenditure during severe caloric restriction. The ergometer exercise for up to two hours daily was well tolerated. The absence of either a training effect or accelerated weight loss in group 2 may be due to the limited duration (4 weeks) or intensity of the exercise.(ABSTRACT TRUNCATED AT 250 WORDS)