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This study was designed to examine effects of alterations in energy balance on adaptive changes in components of total energy expenditure (TEE). Nineteen young healthy males were studied during a 10-day sedentary energy balance baseline period and then randomly assigned to one of four 10-day treatment groups: 1) no change in energy intake (EI) or physical activity (PA; energy balance at low energy flux), 2) EI increased by 50% with no change in PA (positive energy balance), 3) TEE increased by 50% by increasing PA, matched by a 50% increase in EI (energy balance at high energy flux), and 4) TEE increased by 50% by increasing PA with no change in EI (negative energy balance). TEE was measured with doubly labeled water, resting metabolic rate (RMR) by indirect calorimetry, and thermic response to feeding (TEF) by indirect calorimetry; energy expenditure of physical activity (EEPA) was estimated by subtracting RMR, TEF, and prescribed PA from TEE. TEE was significantly increased by PA (by design) but not EI. There was a significant main effect of intake and a significant intake-by-activity interaction for changes in RMR. In post hoc analysis, RMR was significantly increased during positive energy balance and energy balance at high energy flux relative to change in RMR when energy balance was maintained at low energy flux. A significant increase in RMR was also noted during negative energy balance after adjustment for change in fat-free mass. There was no significant difference in change in RMR among the three treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)

To determine the effects of cafeteria feeding on brown (BAT) and white (WAT) adipose tissue cellularity, thermogenesis and body composition, male Sprague-Dawley rats were fed a cafeteria or a Purina chow diet for 52 days postweaning. Interscapular BAT (IBAT) was removed from subgroups of rats on each diet, and the animals continued on the same regimens. The IBAT weight of rats fed cafeteria diets was 160% of controls after 3 days and 220% after 52 days of the dietary regimens, and brown adipocyte numbers were 130 and 300% those of stock diet-fed rats, respectively, during the same period. Brown adipocyte diameters were initially greater in rats fed cafeteria diet than in rats fed stock diet but were similar after 52 days. Norepinephrine-stimulated thermogenesis was greater in rats fed cafeteria diets than in rats fed stock diet and was intermediate between the two in the IBAT-lipectomized group fed cafeteria diet. Surgical reduction of IBAT resulted in hypertrophy of WAT and an improved efficiency of weight gain, whereas body composition, WAT cellularity, and the efficiency of weight gain of similarly operated rats fed stock diet were unaltered from those of unoperated animals fed stock diet. These results are consistent with the development of a nutritionally induced hyperplasia and/or differentiation of BAT similar to that which follows cold acclimatization. BAT may play an active role in the expenditure of excess energy during periods of overnutrition, and thereby influence an animal's propensity for fatness.

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.

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.

To assess whether thermogenesis or sympathetic nervous system (SNS) function might differ between lean and obese human subjects, studies of thermic and sympathetic responses to standard stimuli were undertaken in Pima Indians, an ethnic group with a high prevalence of obesity. Plasma levels of norepinephrine (NE) and energy expenditure at rest and in response to feeding, exercise, and graded infusions of NE were compared in five lean and five obese Indians during a period of weight maintenance (WM), after 3 weeks of overfeeding (OF) and, in the obese, also after 6 weeks of underfeeding (UF). Basal energy expenditure, when adjusted for fat free mass, was equivalent during WM and increased 3% with OF (P less than 0.01) in both groups. Thermic responses to exercise or a test meal did not differ in lean and obese and did not change with OF, while thermic responses to NE infusion fell during OF to a greater degree in obese than lean (P less than 0.05). A similar pattern (decreased effect in obese with OF) was also noted in the glycemic response to infused NE (P less than 0.05). Although not quantitatively different in lean and obese, the plasma NE concentration appeared to vary more in response to feeding or dietary alteration in the obese than lean, a finding that may reflect lower plasma clearance of NE in the obese. These studies, therefore, raise the possibility that overfeeding in obese Pima Indians may limit the contribution of sympathetically mediated thermogenesis to energy expenditure, though the implications of this for body weight regulation are speculative.

The characteristics of regional brown (BAT) and white adipose tissue (WAT) growth and of thermogenesis following experimental overfeeding were studied in groups of male Sprague-Dawley rats fed lab chow or cafeteria diets for 8 weeks postweaning. Regional BAT and WAT growth was determined by dissection and weighing, and thermogenesis was characterized by measurements of resting and norepinephrine (NE)-stimulated oxygen consumption, of serum thyroid hormone concentrations, and of 24-hour urinary NE excretion levels. Cafeteria feeding resulted in a 113% increase in total BAT, with the most prominent increases in the interscapular, thoracic, and perirenal regions. Retroperitoneal, epididymal, and omental WAT were significantly greater in cafeteria than in chow-fed rats. Resting oxygen consumption of cafeteria-fed rads increased by 10% and NE excretion by 64% compared to chow-fed controls, while serum T3 concentrations were nearly doubled in the cafeteria-fed rats. The thermogenic response to NE injection in cafeteria-fed rats was 102% of their resting levels, compared to a 51% increase in the chow-fed controls. The results indicate that increased BAT growth occurs in all primary BAT depots following cafeteria-feeding in rats, and that the greater BAT mass is qualitatively proportional to their greater capacity for non-shivering thermogenesis. Also, the increased NE excretion and greater serum T3 concentration are consistent with increased sympathetic and thyroidal activity and may in part explain the thermogenic response to diet in the rat.

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.

Serum 3,5,3'-triiodothyronine (T3) is increased by overnutrition and decreased by starvation. The production rate of T3 was increased by overfeeding (82%), but T4 production did not change. Feeding a weight maintenance diet with high CHO mimiced serum T3 and rT3 changes of overfeeding, substitution of CHO by FAT those of starvation. VO2 increased during overfeeding and in T4 equilibrated volunteers supplemented with 40 microgram T3 daily for 2 weeks. No weight change occurred in the latter subjects. Yet no decrease in VO2 was found when serum T3 was reduced by the administration of iopanoic acid. VO2 decreased during starvation in normal and hypothyroid rats, and in hypothyroid animals replaced with T4 or T3.