Marcia Statt

Total and resting energy expenditure in obese women reduced to ideal body weight.

Obesity could be due to excess energy intake or decreased energy expenditure (EE). To evaluate this, we studied 18 obese females (148 +/- 8% of ideal body weight [IBW], mean +/- SD) before and after achieving and stabilizing at IBW for at least 2 mo and a control group of 14 never obese females (< 110% of IBW or < 30% fat). In the obese, reduced obese, and never obese groups, the percent of body fat was 41 +/- 4%, 27 +/- 4%, and 25 +/- 3%; total energy expenditure (TEE) was 2704 +/- 449, 2473 +/- 495, and 2259 +/- 192 kcal/24 h; while resting metabolic rate was 1496 +/- 169, 1317 +/- 159, and 1341 +/- 103 kcal/24 h, respectively. 15 obese subjects who withdrew from the study had a mean initial body composition and EE similar to the subjects who were successful in achieving IBW. In 10 subjects followed for at least one year after stabilizing at IBW there was no significant relationship between the deviation from predicted TEE at IBW and weight regain. These studies indicate that, in a genetically heterogeneous female population, neither the propensity to become obese nor to maintain the obese state are due to an inherent metabolic abnormality characterized by a low EE.

Reduced metabolic rate during β-adrenergic blockade in humans☆

We previously reported that 1 week of propranolol treatment (160 to 240 mg/d, orally) reduced resting metabolic rate (RMR) an average of 9% in healthy men. To determine whether this response was caused by the 25% reduction in serum triiodothyronine (T3), rather than β-adrenergic blockade, we examined the effect of nadolol on RMR in five healthy men. Nadolol is a nonselective β-adrenergic antagonist that does not affect T3 production. After 6 to 10 days of nadolol treatment (240 mg/d), mean postabsorptive RMR declined 7% (P < .01), with no significant change in serum T3 or thyroxine (T4) concentrations. This effect is significantly different from that of a hospitalized control group that received no drug and had no change in mean RMR, and was not different from the response to propranolol (previously published data). Nadolol slightly reduced the mean thermic response to a meal (12%), but this effect was not statistically significant. Mean postprandial RMR was 8% lower after nadolol treatment (P < .01), mainly because of the reduced postabsorptive RMR, rather than a change in the response to the meal. These data suggest that β-adrenergic activity makes a small but significant contribution to resting energy expenditure in man.

Increased protein turnover in obese women

Some previous studies have indicated that rates of proteolysis and protein synthesis are greater in obese than in lean subjects, whereas others have not supported this finding. In the present study, we have measured postabsorptive protein turnover in a large group (n = 24) of obese women to establish more conclusively whether obese women have higher rates of protein turnover than lean women (n = 12), and to determine whether obese subjects with the greatest abdominal fat accumulation or those with the most severe insulin resistance (as determined by oral glucose tolerance testing) have the highest rates of protein turnover. Leucine appearance rate (Ra) was used as an index of whole-body proteolysis, and the fraction of Ra not oxidized was used as an index of whole-body protein synthesis. Leu Ra, oxidation, and incorporation into protein after an overnight fast were approximately 25% greater in obese than in lean women, and were approximately 10% to 15% greater after dividing by lean body mass (LBM) or adjusting for LBM by analysis of covariance. Among obese women, the degree of obesity (over the range of 30% to 47% fat) was not a significant determinant of protein turnover, nor were degree of insulin resistance, visceral fat accumulation (determined by magnetic resonance imaging [MRI]), or subcutaneous abdominal fat accumulation (also determined by MRI). However, the women with the highest rates of protein turnover also had higher waist to hip circumference ratios (WHR). We conclude that even moderate obesity is associated with increased protein turnover, and that this effect is not completely explained by the higher LBM in obese subjects.

Differential effect of insulin on whole-body proteolysis and glucose metabolism in normal-weight, obese, and reduced-obese women

The whole-body rate of proteolysis, as indicated by the postabsorptive appearance rate (Ra) of leucine, is increased in obese women. The present study was conducted to examine the hypothesis that the increased proteolysis is explained by insulin resistance, and to determine if proteolysis returns to normal when obese women reduce to normal weight. The mean basal leucine Ra was 21% higher in 31 obese women (> 135% ideal weight) than in 17 normal-weight women, and 9% higher per kilogram lean body mass ([LBM] P > .05). When 17 of the obese women reduced and stabilized at 100% to 116% of ideal weight, their mean basal leucine Ra decreased 17% (7%/kg LBM) and was not significantly different from that of the normal-weight control group. Insulin (40 mU/m2/min) was infused for 2 hours while maintaining euglycemia in eight normal-weight, 14 obese, and eight reduced-obese subjects. Glucose disposal per kilogram LBM was 29% lower in obese than in normal-weight subjects (P < .05) and was normal in the reduced-obese subjects. Insulin suppressed the leucine Ra an average of 18.4% in the control group, 20.4% in the obese group, and 24.1% in the reduced-obese group. Suppression of the leucine Ra by insulin did not correlate with the waist to hip ratio (WHR), glucose disposal rate, or basal leucine Ra. We conclude that the increased basal proteolysis of obese women is reversed by weight loss, and is not caused by insulin resistance.

The effects of weight reduction to ideal body weight on body fat distribution

Obesity is a well-known health risk factor. Several studies have demonstrated that upper-body fat distribution plays a major role in the association between increased adiposity and metabolic disorders. The present study was undertaken to evaluate changes in intraabdominal and subcutaneous fat areas in obese subjects undergoing a weight reduction to their ideal body weight (IBW), as defined by a body mass index (BMI) no greater than 21 or body fat less than 30%, and compare the fat distribution at IBW with that of never-obese control subjects. We studied 33 obese women (151% +/- 1% of IBW; BMI, 31.6 +/- 2.5 [mean +/- SE]) before and after weight loss and a control group of 16 never-obese women (101.0% +/- 1.0% of IBW; BMI, 21.2 +/- 1.1). Eighteen obese women successfully achieved and stabilized at IBW for at least 2 months. Nonsuccessful obese subjects were significantly younger than reduced-weight subjects, but other physical characteristics were similar. In obese, reduced-obese, and never-obese groups, weight was 85 +/- 2.0, 62 +/- 1, and 58 +/- 1 kg; percent body fat was 41% +/- 1%, 24% +/- 2%, and 23% +/- 1%; intraabdominal fat area was 82 +/- 5, 28 +/- 3, and 25 +/- 4 cm2; waist subcutaneous fat area was 275 +/- 15, 120 +/- 9, and 81 +/- 7 cm2; hip subcutaneous fat area was 416 +/- 17, 204 +/- 10, and 195 +/- 7 cm2; and waist to hip ratio (WHR) was 0.84 +/- 0.02, 0.77 +/- 0.01, and 0.73 +/- 0.01, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanism of Glomerular Hyperfiltration After a Protein Meal in Humans: Role of hormones and amino acids

OBJECTIVES Previous studies demonstrated that protein meals and amino acid (AA) infusions increase glomerular nitration rate (GFR) and renal plasma flow (RPF) and that somatostatin (SRIH) infusion inhibits these increments. We tested whether a single AA such as alanine could increase GFR and RPF and whether the changes in GFR and RPF could be explained on the basis of changes in glucagon, growth hormone (GH), and insulin. RESEARCH DESIGN AND METHODS In the first experiment, alanine was infused with or without SRIH in five normal subjects. In the second experiment, five other subjects were infused with SRIH on three separate occasions. In a control study, insulin, glucagon, and GH were given at replacement doses; in a hyperglucagonemia study, glucagon was given at a rate of 0.2 μ · kg−1 · h−1 (hypoglucagonemia); and in a high GH study, GH was given at a rate of 2 /μg · kg−1· h−1. GFR and RPF were measured using inulin and para-aminohippurate, respectively. RESULTS Alanine increased GFR and RPF, whereas SRIH inhibited these changes (P < 0.05). Hyperglucagonemia or high GH with or without insulin failed to increase RPF or GFR. CONCLUSIONS A single AA such as alanine increases GFR and RPF, and this increase is dependent on a factor inhibited by SRIH. Although GH, glucagon, and insulin are factors inhibited by SRIH, none of these factors explains the changes in RPF and GFR in our acute studies.