Effect of age on protein conservation during very-low-energy diet in obese Sprague-Dawley rats.

OBJECTIVE: To examine the effect of age on body protein losses occurring during severe energy restriction in obesity. RESEARCH METHODS AND PROCEDURES: Weanling (young) Sprague-Dawley rats (YR) were fed a high fat (35% energy) diet (HFD) until mean body weight approached that of a group of chow-fed retired breeder (aged) rats (AR). Both groups were then fed HFD for an additional 2 weeks, after which selected controls from YR and AR groups were killed for baseline carcass analysis. Remaining rats were fed a very-low-energy diet (VLED, 33% kcal of HFD) for 3 weeks and then killed for carcass analysis. RESULTS: YR had greater fat stores before VLED, and lost proportionately more fat and less protein during VLED than did AR. Weight loss composition during VLED was 66.7% fat, 11.1% protein, and 22.2% water in YR, and 39.4% fat, 26.2% protein, and 34.3% water in AR. Greater YR fat loss during VLED (70.6+/-30.4 vs. 32.6+/-29.1 g in AR; mean+/-SD) was paralleled by significantly larger decreases in epididymal and retroperitoneal fat pad weights, mean adipocyte size, and lipoprotein lipase activity. Greater protein loss in AR (21.6+/-13.9 g vs. 11.8+/-10.7 g in YR) coincided with larger decreases in visceral organ weights and serum thyroxine and triiodothyronine. Energy expenditure changes during VLED were similar between groups. DISCUSSION: Dietary obese young rats appear better able than aged rats to conserve body protein while losing body fat during severe energy restriction.

Resting energy expenditure in the obese: a cross-validation and comparison of prediction equations.

OBJECTIVE: To examine the accuracy and precision of 12 equations or tables for predicting resting metabolic rate (RMR) in obese persons. DESIGN: Observational (correlational) study. SETTING: Obesity Research Center, St Luke's/Roosevelt Hospital, New York, NY. SUBJECTS/SAMPLES: One hundred twenty-six (73 women, 53 men) healthy, obese subjects recruited through the Obesity Research Center's Weight Control Unit. MEASURES: RMR by indirect calorimetry. Weight and height were measured to the nearest 0.1 kg and to the nearest 1 cm. STATISTICAL ANALYSES PERFORMED: Bivariate regression of predicted RMR on measured RMR; paired t tests for the difference between means of predicted RMR and measured RMR. RESULTS: Of the 12 prediction equations, 6 had intercepts or slopes that were significantly different from 0 and 1, respectively. With two exceptions, the equations accounted for between 56% and 63% of the variance in measured RMR. The Robertson and Reid (1952) equation and the Fleisch (1951) equation performed best with our obese sample. APPLICATIONS/CONCLUSIONS: The Robertson and Reid (1952) and the Fleisch (1951) equations are recommended for clinical use with obese patients.

Clinical correlates of short- and long-term weight loss.

This study was designed to identify psychological, behavioral, and physiological correlates of short- and long-term weight loss. Measures of psychological functioning, body composition, fat cell size and number, and attendance were evaluated in 76 obese women for their relationship to weight loss at the end of treatment and at a 1-y follow-up evaluation. Losing more weight during the first month of treatment and attending a higher percentage of treatment sessions were strongly associated with greater weight loss at the end of treatment and at 1-y follow-up. In addition, patients with the highest initial weights lost the most weight both at the end of treatment and at 1-y follow-up. Easily obtained measures are as successful in predicting weight loss as are more expensive and complicated measures.

Height-normalized indices of the body's fat-free mass and fat mass: potentially useful indicators of nutritional status.

Expressing fat-free mass (FFM) and body fat mass (BFM) as percentages of body weight or by weight is unsatisfactory. For example, tall patients with protein-energy malnutrition (PEM) can exhibit values for FFM and BFM similar to those of shorter well-nourished individuals. To obviate such difficulties, we propose use of height-normalized indices, namely, a FFM index [FFM (kg)/height (m)2, or FFMI] and a BFM index [BFM (kg)/height (m)2, or BFMI]. We calculated these indices in a reference population of 124 healthy young men and in 32 nonobese young men (from the Minnesota Study) before, during, and after experimental semistarvation. When values for FFMI and BFMI falling below the reference cohort's 5th percentile cutoff point were used as a criterion for PEM, these indices, together with basal oxygen-consumption rate, diagnosed PEM in 27 of the 32 Minnesota Study subjects after 12 wk of semi-starvation. These findings indicate that FFMI and BFMI may be useful in nutritional assessment.

Weight loss and change in resting metabolic rate.

The relation between change in resting metabolic rate (RMR) and change in fat-free mass (FFM) after weight loss is not well understood and is often inappropriately expressed in kilocalories per unit of FFM. We measured RMR and FFM in 35 obese patients enrolled in a conservative weight-loss program. RMR per kilogram FFM was not different after weight loss. However, the regression of delta RMR on delta FFM revealed that the decline in RMR tended to be greater than could be accounted for by loss of FFM. At initial test and retest, body fat (Fat) was not a predictor of RMR after FFM had been taken into account but delta Fat significantly contributed to the prediction of delta RMR when added to the equation after delta FFM. Thus, people losing larger amounts of weight had declines in RMR greater than could be accounted for by loss of FFM. Self-reported age of onset of obesity was not related to delta RMR.

Calorie restriction and iopanoic acid effects on thyroid hormone metabolism.

We measured the effects of iopanoic acid on thyroid hormone metabolism in obese men during severe calorie restriction to study the nutrition regulation of thyroid hormone metabolism. Eight morbidly obese men received a weight-maintenance diet followed by 6 wk of 600 kcal/d. During underfeeding, patients received iopanoic acid or placebo for 2-wk periods in a double-blind crossover fashion. Underfeeding alone (UF) produced a 28.3% decline in the serum triiodothyronine (T3) concentration, and iopanoic acid plus underfeeding (IOP) produced a 49.5% decline in T3 concentration from baseline. Serum reverse T3 concentrations increased 289% during IOP compared with UF alone (p less than 0.001). Serum TSH concentration was unchanged by underfeeding but increased twofold during IOP treatment. Thyroid hormone kinetics demonstrated a decrease in T3 production during IOP compared with UF. These findings suggest that calorie restriction regulates T3 production by modulating only type I 5'-deiodinase activity.

Refeeding after fasting in rats: effects of duration of starvation and refeeding on food efficiency in diet-induced obesity.

Rats with diet-induced obesity starved for 8, 15, and 25 d lost liver and muscle glycogen, excess protein, and fat in proportion to duration of starvation. Fat-cell size decreased but fat-cell number did not. Upon refeeding, body fat was only partly restored, with further increase in adipocyte hyperplasia occurring in the starved obese rats. In contrast, fat-cell size was restored to near that of the prefasting value in the starved controls (dry-food-fed, fasted 4 d) after refeeding. With refeeding, food efficiency increased only if starvation had caused a reduction of adipocyte size below normal. Change in food efficiency was not associated with decreases in total carcass protein, specific tissue proteins, or glycogen stores but was correlated with degree of adipocyte filling. It is possible that adipose tissue status somehow modulates energy-dissipating mechanisms.

Resting energy expenditure, body composition, and excess weight in the obese.

This study investigated differences between measured and predicted resting energy expenditure (REE) in 80 women who averaged 104.6 kg in weight and were 49 kg and 88% overweight. Body composition analysis showed that 68% of the excess weight was fat and 32% was fat-free mass (FFM). Normalized for height, total body potassium (TBK) was 113 +/- 15% and total body water (TBW) was 133 +/- 21% of values in nonobese controls. The health of the FFM, defined as the potassium content per kg of FFM, was 84 +/- 13% of normal. Measured and predicted REE were only modestly related (r = +.59), and only 59% of measured REEs were within 10% of predicted values. A stepwise multiple regression indicated that weight was the single best predictor of measured REE and that the size of the FFM made a significantly greater contribution to REE than did the size of the fat mass. Commonly used equations for the prediction of REE are not appropriate for moderately or severely obese patients. Caloric prescription for weight reduction must be tailored to individuals rather than recommending the same caloric intake to persons with varying metabolic rates.

Serum insulin and blood pressure in an obese population.

Serum insulin has been implicated as a determinant of blood pressure (BP) level in obese hypertensive individuals. We examined the relationships among fasting insulin, mean arterial pressure (MAP), body composition, and fat distribution in 204 subjects unselected for glucose tolerance. All met the criteria of taking no oral hypoglycemic agents, insulin or antihypertensive medications. 95 percent were considered obese and 78 percent were female. Mean age was 39 years (range 15-71), percent ideal body weight (IBW) 171 percent (109-332), BP 125/81 mmHg (80-181/50-110) and fasting insulin 44 microU/ml (4-196). Lean body mass (LBM) and body fat were measured by tritium dilution. The correlation coefficient between insulin and MAP was 0.32 (P less than 0.0001). Both insulin and MAP correlated highly with percentage IBW, percentage body fat, fat mass, LBM, body build and upper fat pattern. Controlling for these variables simultaneously eliminated the association between insulin and BP. By contrast, the correlations between MAP and measures of body composition and fat distribution retained significance after controlling for insulin level. These findings suggest that measures of body composition and fat distribution have a relationship with BP that is not entirely accounted for by serum insulin level, and the relationship between serum insulin and BP is indirect and largely accounted for by their mutual association with measures of body composition and fat distribution.

The relative contribution of body fat and fat pattern to blood pressure level.

Although the association between body weight and blood pressure is irrefutable, body fat mass and blood pressure level may not necessarily be directly related. To clarify the relative contribution of fat mass to blood pressure level, we analyzed data on 399 adults consecutively entering a weight control program. Although most subjects were notably overweight (mean ideal body weight 177%), the population represented a wide spectrum of body weights and blood pressure levels. Study parameters included body fat mass (by total body water, 40K, and Steinkamp formula), lean body mass, body build (chest to height ratio), fat cell number and size from bilateral buttock biopsy specimens, upper fat pattern by arm to thigh circumference ratio, and central fat pattern by subscapular to triceps skinfold ratio. Our results concurred with previously noted correlations between obesity and blood pressure (as mean arterial pressure): weight (r = 0.44), percentage of body fat (r = 0.19), and absolute fat mass (r = 0.38; all p less than 0.01); however, lean body mass, age, and body build correlated highly with both fat mass and mean arterial pressure, thereby confounding this relationship. Multivariate analysis was performed to evaluate the relative contribution of fat mass to mean arterial pressure in the presence of these and other potentially confounding variables. Lean body mass, age, body build, and an upper body fat pattern were found to contribute significantly to the variation in mean arterial pressure (p less than 0.01). In their presence, percentage of body fat, absolute fat mass, central fat pattern, fat cell characteristics, and age of onset of obesity did not significantly improve the predictability of mean arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Energy depot replenishment in rats during refeeding after fasting: effect of exercise.

The effect of progressive moderate exercise on body weight gain, visceral and muscle protein stores, and thyroid hormone levels during an 8-day refeeding period after 65 h of starvation was studied in 2-month-old male Sprague-Dawley rats. Twenty-four animals were divided into three groups and acclimated for 5 days while being fed with ordinary Purina Chow. After the fasting phase, a group of rats was killed in order to provide base-line information concerning fasting-induced changes in body composition; a sedentary group was fed Purina Chow ad libitum; and a treadmill-exercised group was pair fed with the sedentary rats. During the refeeding phase, the exercised animals regained significantly less weight than the sedentary animals (p less than 0.001), but the two groups did not differ significantly with respect to visceral, muscle, eviscerated carcass, and skin protein. Total body fat content was lower in the exercised than the sedentary group. The thyroid hormone levels were not significantly different for the two refed groups. These results indicate that exercise during refeeding may alter the pattern of body weight gain during refeeding after fasting such that the replenishment of adipose tissue stores is reduced without compromising the restoration and growth of lean tissue.

Variability in body protein loss during protracted, severe caloric restriction: role of triiodothyronine and other possible determinants.

Six morbidly obese subjects were maintained in a metabolic ward for 64 days on liquid diets providing 600 to 800 kcal/day. Three received protein at a level of 1.5 g/kg desirable weight per day. The other three were given an identical diet in which half the protein was replaced by carbohydrate. Because there were no significant differences in either mean protein or mean fat losses between the two groups, the data on all six subjects were combined. Over the 64 days, the mean weight loss (+/- SEM) of the subjects per 1000 kcal deficit was 174.3 +/- 25.5 g. The composition of this weight loss was 36.0% water, 58.9% fat, and 5.1% protein. Although the rate of fat loss was relatively constant throughout the study, wide interindividual variations in cumulative protein (nitrogen) deficit were observed. Total nitrogen losses per subject ranged from 90.5 to 278.7 g. Cumulative nitrogen loss during the first 16 days tended to correlate negatively with initial mean fat cell size and positively with initial lean body mass. Most notable was the strong negative correlation between the size of the decrease in serum triiodothyronine over the 64-day study and the magnitude of the concurrent cumulative N deficit. During severe caloric restriction, one's ability to decrease circulating serum triiodothyronine levels may be critical to achievement of an adaptational decrease in body protein loss.

Cardiac dysfunction in obese dieters: a potentially lethal complication of rapid, massive weight loss.

During 1977 and 1978, 17 obese but otherwise healthy adult Americans died suddenly of ventricular arrhythmias during or shortly after completing rapid, massive weight reduction induced by very low-calorie diets consisting largely of collagen hydrolysates for 2 to 8 months. A reexamination of the data on these victims has disclosed a significant positive correlation (r = 0.824) between their prediet body mass index and their duration of survival on the very low-calorie diets. Since body mass index reflects degree of fatness, this observation indicates that the ability to defer the lethal effects of severe caloric restriction was a function of the proportion of body fat before dieting. During caloric reduction, the ratio of nitrogen loss to weight loss is inversely related to body fat content; accordingly, we suggest that the fattest dieters survived the longest because they were better able to conserve body (and myocardial) protein. Also, obese people have an enlarged lean body mass which may afford additional protection.

A new method for estimation of body composition in the live rat.

Measurement of total body electrical conductivity (TOBEC) has been used to estimate lean and fat content of meat based on the principle that electrical conductivity of lean tissue is far greater than that of fat. This approach was used to estimate body composition of live rats. An instrument designed for commercial analysis of ground meat (DjMe 100) was used to measure TOBEC in 30 male Sprague-Dawley rats (197-433 g). Individual TOBEC values were obtained in 20 seconds and repeated twice for each rat. The animals were then killed with ether, hair was shaved, lungs collapsed and body density measured hydrostatically. Carcasses were homogenized and analyzed for fat, nitrogen, and water. A high correlation was found between TOBEC and lean body mass by densitometry (r = .97) and between TOBEC and fat-free mass derived from direct carcass analysis (r = .97). Rats weighing up to 450 g could be accommodated in this particular instrument. Measurement of TOBEC should prove useful in estimating body composition and monitoring its changes in live rats and other small laboratory animals.

Prediction of the resting metabolic rate in obese patients.

Resting metabolic rate (RMR) was measured in 154 women and 48 men before the beginning of a weight reduction program. In both sexes there were significant univariate correlations between RMR and fat-free mass, body fat, weight, fat cell weight, and fat cell number (from total body water). Women also showed significant correlations between RMR and fat cell number (from total body potassium), free triiodothyronine index, and fasting and postglucose insulin levels. Multiple regression analysis showed that both fat-free mass and fat cell weight and number were significant predictors of RMR. The contribution of fat-free mass was three to five times greater per kg than that of body fat. There was no significant contribution of thyroid hormones or insulin to the prediction of RMR. Fat cell number and fat cell weight were significant predictors of RMR, whether determined from body water, body potassium, or a formula using both water and potassium. There was no significant difference in regression coefficients between men and women. Thus the difference in RMR between the sexes is probably caused by the higher proportion of fat-free mass in men. The effect of age was small and not statistically significant.

Refeeding after fasting in the rat: effects of dietary-induced obesity on energy balance regulation.

Obesity was induced in male Sprague-Dawley rats by overfeeding a cafeteria-style diet. The obesity was characterized by both adipocyte hypertrophy and hyperplasia. Body weight was then reduced by starvation to match that of control animals that had been fed ordinary Purina Chow. The previously obese rats were then refed to match the same body weight as controls, or given the same amount of Purina Chow as consumed by the controls. This resulted in a remaining moderate obesity, now due only to adipocyte hyperplasia with normal fat cell size. The previously obese rats needed less energy to keep their body weight equal to controls, and they spontaneously ate less than controls. They were, however, less food efficient because they did not accumulate as much energy in fat and protein depots during the period of refeeding as the controls did, and consequently must have transformed more energy into heat. This is in sharp contrast to nonobese animals subjected to a similar experimental procedure. Lipogenic enzymes and lipoprotein lipase activity in adipose tissue as well as plasma insulin concentrations were elevated in overfed rats but normalized during refeeding of Chow after fasting.

Refeeding after fasting in the rat: effects of carbohydrate.

In order to find ways to modify adaptations during refeeding after fasting the amount of carbohydrate fed during refeeding was varied, or its absorption slowed by a glucosidase inhibitor. Exchanging dietary carbohydrate with fat diminished refeeding adaptations in carbohydrate pathways (glycogen contents of liver and muscle, glucose incorporation into carbondioxide, and triglyceride in adipose tissue), but instead facilitated lipid storage (weight of and lipoprotein lipase activity in adipose tissue). An early specific effect of carbohydrate refeeding was an increase in the insulin response in glucose metabolic pathways in adipose tissue. Inhibiting carbohydrate absorption by a glucosidase inhibitor (Acarbose) caused a delay in energy accumulation during refeeding both in glycogen stores, and, more markedly, in adipose tissue triglyceride stores. These data are consistent with the interpretation that the drug prevents or delays carbohydrate uptake, and causes less adaptations of adipose tissue metabolic pathways for lipid storage. The tissue adaptations during refeeding after fasting seem to depend on the energy substrate reaching these tissues.

Refeeding after fasting in the rat: effects on body composition and food efficiency.

Adult male Sprague-Dawley rats were fasted for 65 h and then refed ad libitum for 8 days, during which time body weight and body composition returned to the levels of nonfasting controls. During refeeding, after a decrease on the lst day, daily food intake was moderately increased above control levels. This compensatory increase after the fast brought the total consumption for the whole period to the same level as for the controls. Thus, a greater body weight increase per gram food consumed ("food efficiency") was achieved during the refeeding period. Starvation-induced energy conservation processes thus seemed to persist during refeeding. This mechanism(s) might participate in causing weight gain after reduction as a treatment for obesity.

Refeeding after fasting in the rat: energy substrate fluxes and replenishment of energy stores.

Rats were fasted and refed and concentrations of plasma glucose, glycerol, triglyceride, insulin, and glucagon as well as glucose kinetics after injection of labeled glucose and glycerol were determined. In addition, concentrations and synthesis in vivo (from tritiated water) and in vitro of glycogen, triglycerides, and protein were followed in liver, muscle, and adipose tissues. The refeeding state after fasting was characterized by a decrease in glucose and triglyceride concentrations in plasma. Glucose turnover rate was increased. Protein losses were repleted, first in the liver then in muscle tissue. Synthesis of glycogen and lipid increased above control in liver and adipose tissue. These results are compatible with an increased outflux during refeeding of different energy substrates from plasma into the depleted protein and energy stores to an extent causing lower concentration of these substrates. Such phenomena might be of importance for energy intake regulation during the phase.