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Original Research Communications |
1 From the Rockefeller University, the Laboratory of Human Behavior and Metabolism, New York, and the Division of Molecular Genetics, College of Physicians & Surgeons, the Department of Pediatrics, The New York Presbyterian Medical Center, Columbia University, New York.
2 Presented in part at the first meeting of the Association for Patient-Oriented Research, May 1999, Atlantic City, NJ. 3 Supported in part by NIH grants DK30583, DK01983, GCRCRR00102, and 2P30DK26687. 4 Address reprint requests to M Rosenbaum, Russ Berrie Medical Science Pavilion, 6th Floor, 1150 Street, Nicholas Avenue, New York, NY 10032. E-mail: mr475{at}columbia.edu.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Objective: We hypothesized that changes in energy expenditure associated with weight gain or loss were due in part to changes in catecholamine release, thyroid hormones, carbohydrate utilization, or a combination thereof.
Methods: Urinary catecholamine excretion, serum thyroid hormone concentrations, and results of 3-h oral-glucose-tolerance tests were examined in obese and never-obese subjects at their usual weights, during weight loss or gain, and at stable weights 10–20% below or 10% above usual.
Results: Urinary norepinephrine excretion decreased significantly during and after weight loss and increased during and after weight gain. Serum concentrations of reverse triiodothyronine increased significantly during and after weight loss, whereas serum concentrations of triiodothyronine increased significantly (by 
0%) during and after weight gain. Serum insulin and glucose concentrations during the oral-glucose-tolerance test increased significantly after weight gain in obese subjects. The percentage change in urinary norepinephrine excretion and in serum concentrations of triiodothyronine were significantly correlated with percentage changes in energy expenditure and with each other.
Conclusions: Changes in body weight were associated with changes in catecholamine excretion and thyroid hormones, which might—by virtue of the effects on energy expenditure—have favored a return to usual body weight. Weight gain induced more apparent insulin resistance in the obese than the never-obese subjects, suggesting a threshold effect of total body fat on this phenomenon.
Key Words: Obesity • diabetes • glucose • catecholamines • thyroid hormones • weight change • energy homeostasis • body weight • adults
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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SUBJECTS AND METHODS |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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± SEM); body mass index, 52.7 ± 4.5 (in kg/m2); 12 women: weight, 132 ± 9 kg; body mass index, 47.2 ± 3.4] and 22 never-obese subjects (14 men: weight, 70 ± 3 kg; body mass index, 22.2 ± 0.5; 8 women: weight, 58 ± 3 kg; body mass index, 18.2 ± 3.1) aged 19–42 y were recruited by advertisement or by physician referral. All subjects were at their maximum lifetime body weights and had maintained these weights within a range of 2 kg for 
6 mo. None of the subjects were taking any medication or consuming a special diet. Subjects whose initial body mass indexes were >28.0 were defined as obese (19). All subjects had normal findings on physical examination and from laboratory evaluations, including thyroid function tests [thyroid-stimulating hormone (TSH), thyroxine (T4), triiodothyronine (T3), T3 resin uptake, and free T4 index], complete blood count, hepatitis A and B serologies, HIV testing, biochemistry panel, urinalysis, and oral-glucose-tolerance tests (see below). The protocol was approved by the Rockefeller University Hospital Institutional Review Board, and written, informed consent was obtained from all subjects.
Experimental design
The subjects were admitted to the inpatient facility of the Clinical Research Center at Rockefeller University at usual body weight (Wtinitial) and were fed a liquid-formula diet [40% of energy as fat (corn oil), 45% as carbohydrate (glucose polymer), and 15% as protein (casein hydrolysate)] supplemented with 5.0 g iodized NaCl, 1.9 g K+ as a potassium salt, 2.5 g CaCO3/d, 1 mg folic acid twice weekly, and 36 mg ferrous Fe every other day. Energy intake was adjusted until body weight was constant [slope of the regression line of body weight (kg) versus time (d) <10 g/d] for 14 d. Once subjects were clearly weight stable, they underwent a series of previously reported tests of energy expenditure [24-h total energy expenditure (TEE) by adjustment of energy to maintain weight and resting energy expenditure (REE) and the thermic effect of feeding (TEF) by indirect calorimetry (20)], body composition [by hydrodensitometry (21)], fat distribution (measurement of waist and hip circumferences), and abdominal and gluteal subcutaneous fat cell lipid content in samples obtained by needle aspiration (22, 23) during an 10-d period while continuing to ingest a weight-maintaining quantity of formula diet. These studies were published previously (1). During this testing period, total urine output was collected over 2 separate 24-h periods for determination of 24-h creatinine concentrations and an aliquot of the 24-h collection was mixed with 0.5 mL of 6 mol HCl/L and assayed for the catecholamines epinephrine, norepinephrine, and dopamine; the CVs for these assays are 6.2%, 5.7%, and 7.1%, respectively (24). Serum concentrations of TSH, T4, T3, and reverse T3 (rT3; the bioinactive enantiomer of T3) were determined by radioimmunoassay (25). The subjects underwent a 3-h oral-glucose-tolerance test in the postabsorptive state at 0900 after administration of 100 g dextrose in a cola-flavored beverage (Cola 100; Stephens Scientific, Riverdale, NJ). Serum glucose was measured by colorimetric assay with a DAX analyzer (Miles Laboratories Inc, Elkhart, IN) and serum insulin was measured by radioimmunoassay (26) at -15, 0, 15, 30, 45, 60, 75, 90, 120, and 180 min relative to the administration of dextrose. Abdominal and gluteal subcutaneous adipose tissues were aspirated by needle biopsy under local anesthesia with 1% xylocaine, and the adipocyte volume (expressed as µg lipid/cell) was determined by using the osmium fixation method of Hirsch and Gallian (23).
After studies at Wtinitial, 13 never-obese subjects and 13 obese subjects were provided a maximum tolerated intake of self-selected foods (generally providing 20920–33472 kJ, or 5000–8000 kcal/d) until they had gained 10% of their initial body weight. No formula was ingested during the period of weight gain, which averaged 4–6 wk in never-obese subjects and 6–10 wk in obese subjects. At the new weight plateau, 10% above Wtinitial (Wt+10%), the formula diet was reinstated and the quantity adjusted to maintain constant body weight. When subjects had been weight-stable (as defined above) for 14 d at Wt+10%, the catecholamine, thyroid, and oral-glucose-tolerance studies described above were repeated. [We showed previously that the metabolic changes that accompany the maintenance of an altered body weight do not represent a carryover effect from the dynamic processes of weight loss or gain (1, 2)]. In addition, to contrast periods of dynamic weight change with those of weight stability, urinary catecholamine and thyroid studies were conducted in obese subjects at the end of the weight-gain period when these subjects had achieved Wt+10% but were not yet consuming a weight-maintenance energy intake. Eight obese women who had undergone weight gain and the maintenance of an elevated body weight at Wt+10% were then provided 3347 kJ (800 kcal)/d of the formula diet until they had returned to their initial weight (Wtinitial2), at which time measurements of urinary catecholamines, thyroid function, and oral glucose tolerance were repeated. Urinary catecholamines and thyroid hormones were measured in these 8 women while they were still losing weight at the end of the period of weight loss until Wtinitial2.
After studies at Wtinitial, 11 never-obese subjects and 12 obese subjects were provided 3347 kJ (800 kcal)/d of the formula diet until they had lost 10% of Wtinitial. The period of weight loss averaged 4–6 wk in never-obese subjects and 6–10 wk in obese subjects. At the new weight plateau (Wt –10%), the formula diet was reinstated and the quantity adjusted to maintain constant body weight. When the subjects had been weight-stable at Wt–10% for 14 d, the catecholamine, thyroid, and oral-glucose-tolerance studies described above were repeated. In addition, at the end of the weight-loss period, when the subjects had achieved Wt–10% but were still ingesting 3347 kJ (800 kcal)/d, urinary catecholamine and thyroid studies were performed in obese subjects. An additional 10 obese subjects then continued losing weight while consuming 3347 kJ (800 kcal)/d until they were at 20% below Wtinitial (Wt–20%), at which time they were again maintained at their new weight, and catecholamine, thyroid, and oral-glucose-tolerance studies were repeated. The protocol is schematized in Figure 1
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10% above usual was associated with an 15% increase in 24-h TEE, a 40% increase in NREE, and a 60% increase in the TEF normalized to fat-free mass (ie, corrected for weight gain–associated changes in fat-free mass). Return to Wtinitial2 was not associated with any significant change in any of these indexes. Maintenance of a reduced body weight (Wt–10% or Wt–20%) was associated with an 15% decrease in TEE, a 10% decrease in REE, and a 20% decrease in NREE, again normalized to fat-free mass. Changes between weight plateaus in each measure of energy expenditure were correlated with changes in 24-h excretion of urinary catecholamines (norepinephrine, epinephrine, and dopamine) and measures of thyroid hormones (T3, T4, rT3, and TSH) to determine whether changes in any component of energy expenditure were significantly correlated with changes in autonomic nervous system tone or thyroid axis function. We reported previously that plasma concentrations of the protein leptin are highly correlated with adipose tissue mass (27). Ahima et al (28) noted that leptin administration blunted the degree of hypothalamic-pituitary-thyroid axis suppression that occurred in mice during starvation conditions, suggesting that there may be a relation between plasma leptin concentration and activity of the thyroid axis. We examined postabsorptive plasma leptin concentrations with a solid-phase sandwich enzyme immunoassay using an affinity-purified polyvalent antibody immobilized in microliter wells (performed by Margery Nicolson; Amgen Inc, Thousand Oaks, CA). Bound leptin was detected with affinity-purified antibody conjugated to horseradish peroxidase and quantified with a chromogenic substrate (tetramethyl benzidine–peroxide). Leptin concentrations were calculated from standard curves generated for each assay by using recombinant human leptin. The minimum detectable leptin concentration in this assay is 20 ng/L. All samples from individual subjects were analyzed in the same assay (27). The leptin data were reported previously (29), but had not been correlated with measures of insulin sensitivity, catecholamine release, or thyroid hormone concentrations. These relations were analyzed in the present study.
Statistical analyses
Within-group comparisons for within-subject effects of changes in body weight were made by two-way analysis of variance (ANOVA) with repeated measures. Comparisons between obese and never-obese subjects were made by two-way ANOVA (30). Analyses of group (obese compared with never-obese) x time (weight plateau) interactions were determined by using multivariate ANOVA with repeated measures. Regression analyses were performed to determine possible relations between energy expenditure, catecholamine excretion, and circulating concentrations of thyroid hormones and leptin at each weight plateau. To determine whether changes in serum thyroid hormones or urinary catecholamine excretion were correlated with each other or with changes in energy expenditure that occur after weight gain or loss, the percentage change in each of these variables between the values at Wtinitial and Wt+10% or Wt–10% was calculated. Least-squares regression analysis was performed to relate changes in serum thyroid hormone and urinary catecholamine excretion with each other and with various compartments of energy expenditure. Normality of distributions was ascertained by using the Wilks-Shapiro test of the residuals from the regression analysis to ascertain that significant correlations were not due to clumping of values in a bimodal distribution after weight gain or weight loss. Unless otherwise noted, data are presented as means ± SEMs. Significance was defined as P < 0.05. Data were analyzed by using STATISTICA (StatSoft, Tulsa, OK)
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RESULTS |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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). Although, as expected, the women initially had a significantly greater percentage of body fat (44.3 ± 3.2%) than did the men (26.3 ± 3.3%; P < 0.001), no significant sex differences in the composition of weight lost or gained were noted. Similarly, as expected, the women had a more peripheral (gynoid) body fat distribution than did the men. The initial waist-to-hip ratio (WHR) and the ratio of abdominal to gluteal fat cell size were significantly lower in the women (WHR: 0.83 ± 0.03; abdominal:gluteal fat cell size: 0.85 ± 0.05) than in the men (WHR: 0.93 ± 0.02; abdominal:gluteal fat cell size: 0.95 ± 0.05), but no significant sex effects on changes in these ratios were noted.
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8 wk later during static weight maintenance. The same changes noted in T3 (an increase after weight gain and a decrease after weight loss), rT3 (an increase after weight loss), urinary norepinephrine excretion (an increase after weight gain and a decrease after weight loss), and urinary dopamine excretion (a decrease after weight loss) during maintenance of an altered body weight were noted during dynamic weight loss or gain (Wt+10% or Wt–10%, respectively). No significant differences in urinary catecholamine excretion or serum thyroid hormone concentrations were found between dynamic weight gain or loss to weights above or below usual and static weight maintenance at the new weight (Wt+10% or Wt–10%). However, urinary dopamine and norepinephrine excretion during weight loss from 10% above initial weight (Wt+10%) back to initial weight (Wtinitial2) were significantly lower than that at initial weight or when weight was stable for 4–6 wk at Wtinitial2, and values were similar to those observed during weight loss to 10% below initial weight. Unlike dynamic weight loss to 10% below initial weight, no significant effect of dynamic weight loss from 10% above initial weight to Wtinitial2 was noted on serum thyroid hormone concentrations. Although TSH was noted to be lower during both dynamic weight loss and gain than at Wtinitial, Wtinitial2, or Wt+10%, these differences were not significant (Table 3).
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). Data in these regression analyses were normally distributed as determined by Wilks-Shapiro testing, ie, there was not significant clumping of data at high and low percentages to account for the significance of the regression. No significant correlations between any of these variables were noted within a given weight plateau, and serum thyroid hormone concentrations and urinary catecholamine excretion were not significantly correlated with the TEF, NREE, or the composition (fat mass compared with fat-free mass) of the weight lost or gained (data not shown).
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where the partial r for the % change in norepinephrine = 0.48 (P = 0.0016) and the partial r for % change in T3 = 0.26 (P = 0.15)
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where the partial r for % change in norepinephrine = 0.39 (P = 0.0016) and the partial r for % change in T3 = 0.07 (P = 0.65), ie, there was no significant improvement in the regression equation over that relating changes in energy expenditure to changes in urinary norepinephrine excretion alone. This analysis suggests that whatever effect the changes in circulating concentrations of T3 exert on changes in energy expenditure must be due to changes in sympathetic nervous system tone.
No significant effects of body fat distribution (defined as the WHR) or waist circumference alone on any of these variables at individual weight plateaus were noted. No significant effect of initial body fat distribution on changes in any of these variables at subsequent weight plateaus was noted.
Carbohydrate metabolism
In the obese subjects, weight gain was associated with a significant increase in the area under the insulin x time and glucose x time curves during oral-glucose-tolerance testing (Table 4). The 50% rise in the area under the insulin x time curve was insufficient to prevent an 30% rise in the area under the glucose x time curve, indicating that the obese subjects were relatively insulinopenic and more resistant to insulin-mediated glucose uptake, at Wt+10%. In contrast, the never-obese subjects showed no significant effects of weight gain on glucose-stimulated insulin release (as measured by area under the insulin x time curve) or insulin-mediated glucose uptake (as measured by the area under the glucose x time curve). No significant effects of weight loss on serum glucose or insulin concentrations were noted in either obese or never-obese subjects at Wt–10%; however, insulin excursions were significantly lower in obese subjects studied at Wt–20% than in the same subjects studied at Wtinitial (Figures 5–8).
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). There was a significant interaction between initial somatotype and the shape of the insulin x time curve such that at Wt+10%, obese subjects had greater insulin release between 30 and 120 min after glucose ingestion than did never-obese subjects at Wt+10%. There was also a significant somatotype effect on the changes in the shape of this curve that occurred after weight gain so that insulin release between 30 and 120 min increased to a significantly greater extent (compared with Wtinitial) in obese subjects than in never-obese subjects after weight gain than in studies at Wtinitial (Table 3). Of the 11 never-obese subjects studied at Wtinitial and Wt+10%, 7 showed an increase in the area under the insulin x time curve and in the ratio of the areas under the insulin x time curve and glucose x time curves (NS). Of the 13 obese subjects studied at Wtinitial and Wt+10%, 11 showed an increase in the area under the insulin x time curve and in the ratio of the areas under the insulin x time curve and glucose x time curves (P < 0.05; paired sign test). Therefore, the differences in the changes in apparent insulin sensitivity (insulin area/glucose area) associated with weight gain between obese and never-obese subjects were not due to differences in variance in the data or to relatively large changes in only a few obese subjects. Neither initial body mass index nor percentage of body fat were significantly correlated with the magnitude of the changes in area under the insulin x time curve after weight gain. No significant effects of initial body fat distribution (WHR) on changes in any of these variables at subsequent weight plateaus were noted.
Fasting concentrations of insulin and glucose and areas under the insulin x time and glucose x time curves during the oral-glucose-tolerance test were regressed against measures of body composition (fat mass, fat-free mass, and body mass index) and body fat distribution (waist circumference, hip circumference, WHR, abdominal subcutaneous adipose tissue volume, gluteal subcutaneous adipose tissue volume, and the ratio of abdominal to gluteal subcutaneous adipose tissue volume) to determine whether there were significant interactions between these variables and whether such interactions were different between obese and never-obese subjects or between men and women. No significant interactions between body composition or fat distribution and any measure of glucose were noted. There were significant correlations of many measures of body composition and fat distribution with fasting insulin concentrations and, to a lesser extent, with area under the insulin x time curves. No significant differences were noted in oral-glucose-tolerance test data between men and women when groups were compared by sex at each weight plateau and within each somatotype group (obese or never-obese). However, regression equations relating areas under the insulin x time curve to measures of body composition were different between men and women, presumably reflecting the sex differences in body composition (higher percentage of body fat in women) and fat distribution (lower WHR and abdominal:gluteal fat cell size in women; see body-composition data above). Significant regression equations by sex are shown in Table 5.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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) suggest that 25–40% of the changes in TEE and REE that occur after weight gain or loss may be the result of changes in catecholamine action. Although correlations of changes in energy expenditure with changes in serum T3 are significant, the addition of changes in serum T3 as an independent variable to equations relating changes in energy expenditure to changes in urinary norepinephrine excretion did not significantly improve the regression coefficients. Therefore, whatever effects the changes in serum T3 exert on changes in energy expenditure appear to be dependent on changes in sympathetic nervous system tone. There was a noteworthy dichotomy in the responses of thyroid hormones and urinary catecholamine excretion to weight loss (to Wtinitial2) after weight gain (to Wt+10%). Weight change (either dynamic or weight maintaining) above or below Wtinitial is associated with significant respective increases or decreases in serum T3, unlike the process by which weight returns to usual after weight gain. On the other hand, significant increases during weight gain and declines during both weight loss from Wt+10% to Wtinitial and to plateaus below Wtinitial were noted in 24-h excretion of norepinephrine. Thus, serum thyroid hormone concentrations are affected only by dynamic change from usual weight as well as by maintenance of an altered body weight, whereas urinary norepinephrine excretion is affected by any dynamic weight change as well as by maintenance of an altered body weight. These data suggest that thyroid status may be responsive to perturbations relative to usual weight (perhaps to changes in body fat stores) rather than to the process of weight loss per se, whereas changes in autonomic nervous system function may be triggered by the process of weight gain or loss per se as well as by changes in body fat relative to usual. The trend toward a decline in TSH during any dynamic weight change is of interest, even though the change was not significant. It is possible that the observed decline in T3 and increase in rT3 during and after weight loss was due, in part, to a central declines in TSH production, whereas the significant increase in circulating T3 concentrations during weight gain represented a change in T3 metabolism, which cause a central TSH suppression.
The lack of change in urinary catecholamine excretion or serum concentrations of thyroid hormones measured at initial weight and after return to initial weight (Wtinitial2) from Wt+10% is in agreement with the results of other studies of catecholamine and thyroid status of "weight cyclers," ie, those who have lost weight and then regained it (33). However, changes in catecholamine excretion during and after weight reduction were not detected in some other studies (34, 35). The present study examined 24-h excretion of catecholamines, whereas previous studies have generally examined plasma catecholamines at isolated time points or urine catecholamines only in the postabsorptive state, or postexercise, state. The higher catecholamine excretion rate in our obese than in our never-obese subjects agreed with the results of previous studies (36). We also did not detect any of the significant increases in adrenergic activity, especially in urinary epinephrine excretion, during hypoenergetic intake that were reported by others (37). This discrepancy may reflect differences in the severity of energy restriction [total fasting to 1674 kJ (400 kcal)/d in other studies compared with 3347 kJ (800 kcal)/d in the present study], differences in the way in which catecholamines were measured (serum concentrations, often in response to standing or exercise in other studies versus 24-h urinary excretion in the present study), or the lack of maintenance of a constant sodium intake in other studies [sodium restriction is associated with an increase in circulating concentrations of norepinephrine (38)].
We detected no significant correlations between plasma concentrations of leptin and measures of thyroid hormone or urinary catecholamine release. The lack of such correlations agrees with our observation that plasma leptin concentrations were not significantly correlated with any measure of energy expenditure at any weight plateau once corrected for body composition (29). Although there is a sexual dimorphism in circulating leptin concentrations and in changes in the relation between leptin and fat mass that occur after weight loss or gain (29), no such dimorphism was noted in the effects of weight changes on thyroid hormones, catecholamine excretion, or carbohydrate metabolism.
There was a sexual dimorphism in the relation between measures of body composition and body fat distribution and insulin sensitivity. For example, there were significant correlations between measures of insulin sensitivity and fat mass or WHR in the men; these correlations were not seen in the women. These correlations, however, were clearly weaker than those reported in other studies (39). The weaker correlations between measures of body fat distribution or abdominal adipocyte volume and insulin sensitivity noted in the present study probably reflect the extensive metabolic screening of our subjects (including oral-glucose-tolerance testing) to exclude subjects with marked insulin resistance or impaired glucose tolerance.
The basis for the sexual dimorphism in the relations of body composition and fat distribution to insulin sensitivity may be due to the relatively larger amounts of body fat in subcutaneous than in visceral depots in women than in men. Visceral adipose tissue constitutes 5% of total fat mass in women and 10% in men (40). A larger visceral adipose tissue depot is associated with decreased insulin sensitivity (41). The mechanism for the association between body fat distribution and morbidity is hypothesized to be the direct drainage of the intraabdominal fat depot into the portal circulation. High concentrations of free fatty acids are thus presented to the liver, resulting in increased synthesis of LDLs and VLDLs and the promotion of insulin resistance by interfering with first-pass metabolism of insulin by the liver (42–44). The significant associations between tissue insulin sensitivity and measures of adiposity and adipose tissue distribution in men in the present study may have been because the size of the visceral adipose tissue depot in men, but not in women, was large enough to significantly affect sensitivity even at Wtinitial, even though none of the subjects had results that would be classified as showing impaired glucose tolerance (45).
Differences between never-obese and obese subjects in circulating concentrations of insulin, but not of glucose, were noted during oral-glucose-tolerance testing. Although it is also possible that the administration of a purely liquid-formula diet (compared with a solid-food diet) affected the results of the oral-glucose-tolerance test, the observed results are consistent with those from studies of subjects consuming less-restricted diets. Increased resistance to insulin-mediated glucose transport is a well-documented effect of obesity (39, 46). It is notable that, even in obese subjects prescreened with an oral-glucose-tolerance test to ensure that they were not diabetic, there were significant increases in insulin resistance associated with weight gain and significant decreases in insulin excursion during the oral-glucose-tolerance test after a 20% weight loss. Such changes did not occur in the never-obese subjects after weight gain. The requirement of greater weight loss than previously reported in obese subjects (14–18) to induce a significant change in insulin excursion may again reflect the extensive prescreening of our subjects. The significant effects of weight gain on the insulin x time curve (to the point of considerable insulin resistance) in obese but not in never-obese subjects suggests that obese subjects are more sensitive to the stress of a 10% weight gain than are never-obese subjects and that obese subjects who may have oral-glucose-tolerance-test results that would be considered "normal" may be at substantial risk of impaired glucose tolerance or overt type 2 diabetes mellitus after even modest degrees of additional weight gain.
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ACKNOWLEDGMENTS |
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 C. Bernal-Mizrachi, S. Weng, B. Li, L. A. Nolte, C. Feng, T. Coleman, J. O. Holloszy, and C. F. Semenkovich Respiratory Uncoupling Lowers Blood Pressure Through a Leptin-Dependent Mechanism in Genetically Obese Mice Arterioscler. Thromb. Vasc. Biol., June 1, 2002; 22(6): 961 - 968. [Abstract] [Full Text] [PDF]
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 C. Pelletier, E. Doucet, P. Imbeault, and A. Tremblay Associations between Weight Loss-Induced Changes in Plasma Organochlorine Concentrations, Serum T3 Concentration, and Resting Metabolic Rate Toxicol. Sci., May 1, 2002; 67(1): 46 - 51. [Abstract] [Full Text] [PDF]
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R. Weinsier, G. Hunter, and Y. Schutz Metabolic response to weight loss Am. J. Clinical Nutrition, March 1, 2001; 73(3): 655 - 657. [Full Text] [PDF]
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M. Rosenbaum and R. L Leibel Reply to R Weinsier et al Am. J. Clinical Nutrition, March 1, 2001; 73(3): 657 - 658. [Full Text] [PDF]
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