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Menopause-related changes in body fat distribution may partially explain the greater risk of cardiovascular and metabolic disease during the postmenopausal years. To date, however, the effect of the menopause transition on body fat distribution remains unclear. Cross-sectional and longitudinal studies using waist circumference or the waist-to-hip ratio show no effect of menopause on body fat distribution. By contrast, studies using dual-energy X-ray absorptiometry showed increased trunk fat in postmenopausal women. Moreover, studies using computed tomography (CT) and magnetic resonance imaging (MRI) show that postmenopausal women have greater amounts of intra-abdominal fat compared to premenopausal women. Collectively, these studies suggest that the menopause transition is associated with an accumulation of central fat and, in particular, intra-abdominal fat. Whether menopause-related differences in trunk or intra-abdominal fat are independent of age and/or adiposity, however, is unclear. Thus, we recently examined the effect of menopausal status on body composition and abdominal fat distribution in 53 middle-aged, premenopausal women (47 +/- 3 years) and 28 early postmenopausal women (51 +/- 4 years). Postmenopausal women had 36% more trunk fat (p < 0.01), 49% greater intra-abdominal fat area (p < 0.01), and 22% greater subcutaneous abdominal fat area (p < 0.05) than premenopausal women. The menopause-related difference in intra-abdominal fat persisted (p < 0.05) after statistical adjustment for age and fat mass, whereas no differences were noted in trunk or abdominal subcutaneous fat. A similar pattern of differences in trunk, subcutaneous, and intra-abdominal fat was observed in subsamples of pre- and postmenopausal women matched for age or fat mass. Our data and that of others suggest that early postmenopausal status is associated with a preferential increase in intra-abdominal fat that is independent of age and total adiposity. Thus, CT and MRI should be used when examining menopause-related changes in body fat distribution.

Physical activity energy expenditure (PAEE) is a determinant of prognosis and fitness in older patients with coronary heart disease (CHD). PAEE and total energy expenditure (TEE) are closely related to fatness, physical function, and metabolic risk in older individuals. The goal of this study was to assess effects of resistance training on PAEE, TEE, and fitness in older women with chronic CHD and physical activity limitations ( N = 51, mean age: 72 + 5 yr). The study intervention consisted of a progressive, 6-mo program of resistance training vs. a control group condition of low-intensity yoga and deep breathing. The study interventions were completed by 42 of the 51 participants. The intervention group manifested a 177 ± 213 kcal/day (+9%) increase in TEE, pre- to posttraining, measured by the doubly labeled water technique during a nonexercise 10-day period ( P < 0.03 vs. controls). This was due to a 50 ± 74 kcal/day (4%) increase in resting metabolic rate measured by indirect calorimetry ( P < 0.01, P < 0.05 vs. controls) and a 123 ± 214 kcal/day (9%) increase in PAEE ( P < 0.03, P = 0.12 vs. controls). Resistance training was associated with significant increases in upper and lower body strength, but no change in fat-free mass, measured by dual X-ray absorptiometry, or left ventricular function, measured by echocardiography and Doppler. Women in the control group showed no alterations in TEE or its determinants. There were no changes between groups in body composition, aerobic capacity, or measures of mental depression. These results demonstrate that resistance training of 6-mo duration leads to an increase in TEE and PAEE in older women with chronic CHD.

A unique subset of individuals termed metabolically obese but normal weight (MONW) has been identified. These young women are potentially at increased risk for development of the metabolic syndrome despite their young age and normal body mass index. We seek to determine metabolic and behavioral factors that could potentially distinguish MONW women from young women with a normal metabolic profile. Ninety-six women were classified as MONW (n 12) or non-MONW (n 84) based on a cut point of insulin sensitivity (as estimated by the homeostasis model assessment). Potentially distinguishing phenotypes between groups measured included serum lipids, ghrelin, leptin, adiponectin, body composition and body fat distribution, resting and physical activity energy expenditure, peak oxygen uptake, dietary intake, dietary behavior, and family history and lifestyle variables. Despite a similar body mass index between groups, MONW women showed higher percent body fat, lower fat-free mass, lower physical activity energy expenditure, and lower peak oxygen uptake than non-MONW women. Plasma cholesterol level was higher in MONW women, whereas no differences were noted for other blood lipids, ghrelin, leptin, adiponectin, and resting energy expenditure. MONW women had lower dietary restraint scores than non-MONW women, but no differences were noted in disinhibition, hunger, and dietary intake. Stepwise regression analysis performed on all subjects showed that 33.5% of the unique variance of the homeostasis model assessment was explained with the variables of percentage of body fat (17.1%), level of dietary restraint (10.4%), and age (6%). Both metabolic and dietary behavioral variables contribute to the deleterious metabolic profile of MONW women. They display lower insulin sensitivity due potentially to a cluster of sedentary behavior patterns that contribute to their higher adiposity. Furthermore, cognitive attitudes toward food (i.e. dietary restraint) and concomitant lifestyle behaviors may play a role in regulating insulin sensitivity in MONW women. (J Clin Endocrinol Metab 89: 5013–5020, 2004)

Obesity is thought to be a heterogeneous disorder with several possible etiologies; therefore, by examining subtypes of obesity we attempt to understand obesity’s heterogeneous nature. The purpose of this review was to investigate the roles of metabolic, body composition, and cardiovascular disease risk in subtypes of obesity. We briefly consider two subtypes of obesity that have been identified in the literature. One subset of individuals, termed the metabolically healthy, but obese (MHO), despite having large amounts of fat mass compared with at risk obese individuals shows a normal metabolic profile, but remarkably normal to high levels of insulin sensitivity. Preliminary evidence suggests that this could be due at least in part to lower visceral fat levels and earlier onset of obesity. A second subset, termed the metabolically obese, but normal weight (MONW), present with normal body mass index, but have significant risk factors for diabetes, metabolic syndrome, and cardiovascular disease, which could be due to higher fat mass and plasma triglycerides as well as higher visceral fat and liver content. We also briefly consider the potential role of adipose and gastrointestinal hormonal profiles in MHO and MONW individuals, which could lead to a better understanding of potential factors that may regulate their body composition. This information will eventually be invaluable in helping us understand factors that predispose to or protect obese individuals from metabolic and cardiovascular disease. Collectively, a greater understanding of the MHO and MONW individual has important implications for therapeutic decision making, the characterization of subjects in research protocols, and medical education.

The physiological factors mediating gender differences in resting metabolic rate (RMR) in older individuals are presently unclear. We examined the contribution of sympathetic nervous system activity to gender differences in resting metabolic rate in older men and women and its relation to body fat distribution. We performed measurements of noradrenaline (NA) kinetics from infusions of [3H]-NA, RMR, body fat distribution, body composition, peak Vo2 and dietary intake in 29 older men (69 +/- 6 years) and 26 older women (65 +/- 5 years). Older men weighed more (P < 0.01) and had a greater fat-free mass (P < 0.01) and a larger waist circumference (P < 0.01) than older women. Older men had a higher RMR (P < 0.05) than older women, which persisted after controlling for differences in fat-free mass and fat mass. Older men also showed a greater NA appearance rate (P < 0.01) at rest than older women. The higher NA appearance rate in older men was partly related to their greater waist circumference (r = 0.50, P < 0.01). We explored the sympathetic contribution to gender differences in RMR by statistically controlling for differences in body composition and NA appearance rate. After this procedure, we found no gender differences in adjusted RMR between older men (4.3 +/- 0.5 kJ min(-1)) and older women (4.3 +/- 0.4 kJ min(-1)). Our results suggest that: (a) older men have a higher RMR than older women independent of differences in body composition; (b) the higher RMR in older men may be partly due to higher levels of sympathetic nervous system activity; (c) the higher sympathetic nervous system activity in older men is partly related to their greater waist circumference, a proxy measure of central body fatness.

We evaluated the value of resistance training on measures of physical performance in disabled older women with coronary heart disease (CHD).The study intervention consisted of a 6-month program of resistance training in a randomized controlled trial format. Training intensity was at 80% of the single-repetition maximal lift. Control patients performed light yoga and breathing exercises. Study participants included 42 women with CHD, allor= 65 yr of age and community dwelling. Subjects were screened by questionnaire to have low self-reported physical function. The primary study measurements related to the performance of 16 household activities of the Continuous Scale Physical Functional Performance test (CSPFP). These ranged from dressing, to kitchen and cleaning activities, to carrying groceries and walking onto a bus with luggage, and a 6-min walk. Activities were measured in time to complete a task, weight carried during a task, or distance walked. Other measures included body composition, measures of aerobic fitness and strength, and questionnaire-based measures of physical function and depression score.Study groups were similar at baseline by age, aerobic capacity, strength, body composition, and in performing the CSPFP. After conditioning, 13 of 16 measured activities were performed more rapidly, or with increased weight carried, compared with the control group (all P0.05). Maximal power for activities that involved weight-bearing over a distance, increased by 40% (P0.05).Disabled older women with CHD who participate in an intense resistance-training program improve physical capacity over a wide range of household physical activities. Benefits extend beyond strength-related activities, as endurance, balance, coordination, and flexibility all improved. Strength training should be considered an important component in the rehabilitation of older women with CHD.

Acta Obstet Gynecol Scand 2002; 81: 603-611. © Acta Obstet Gynecol Scand 2002 Objectives. The effects of menopause transition on metabolic and cardiovascular disease risk in women are unclear. It is unknown whether estrogen deficiency, aging, or a combination of both factors are independent contributors to a worsening health profile in women. We considered the effects of menopause transition and hormone replacement therapy on body composition, regional body fat, energy expenditure, and insulin sensitivity. Methods. A brief review of current literature that has considered the role of menopause transition and hormone replacement therapy on body composition, energy expenditure, and insulin sensitivity with an emphasis on longitudinal investigations. Results. Preliminary evidence suggests that natural menopause is associated with reduced energy expenditure during rest and physical activity, an accelerated loss of fat-free mass, and increased central adiposity and fasting insulin levels. Hormone replacement th...

The Trp64Arg polymorphism in the [beta ] 3 -adrenoceptor gene has been associated with increased prevalence of obesity, type 2 diabetes, and low rates of energy expenditure, although these findings are not unanimous. It is currently unknown if the presence of the Trp64Arg gene variant impedes the loss of body weight in obese, postmenopausal women via a reducing effect on energy expenditure. The objective of this study was to compare body composition and energy expenditure in carriers and noncarriers of the Trp64Arg variant in the [beta ] 3 -adrenoceptor before and after weight loss. We measured body composition, total daily energy expenditure (TEE), resting metabolic rate (RMR), physical activity energy expenditure (PAEE), thermic effect of feeding (TEF), and respiratory quotient (RQ) in 34 obese, postmenopausal women (19 carriers and 15 noncarriers for the Trp64Arg variant) before and after a weight loss intervention. There were no differences in body composition or daily energy expenditure and its components between the 2 groups at baseline. There were significant reductions in body mass, body mass index (BMI), percent body fat, fat-free mass, and fat mass (main effect, all P [lt ] .0001) when analyzed with the 2 genotypes combined, but no significant differences between carriers and noncarriers with respect to change in these variables (group [times ] time interaction term, all P [gt ] .05). Total energy expenditure tended to be reduced (490 kJ [middot] d [minus ]1 , P = .13) in both groups following weight loss, but there was no significant group [times ] time interaction term ( P = .78), indicating no difference in the response of the 2 genotypes. There was a 9% reduction in RMR (611 kJ [middot] d [minus ]1 , P [lt ] .001) when both groups were considered together, but no significant group [times ] time interaction term ( P = .84), suggesting that both groups responded in a similar manner to the weight loss intervention. PAEE and the TEF were not different following weight loss (both P [gt ] .60). There was a trend for RQ to be reduced after weight loss ( P = .07), but there was no difference between carriers or noncarriers of the Trp64Arg variant ( P = .58). In summary, we found that obese postmenopausal women who carry the Trp64Arg variant in the [beta ] 3 -adrenoceptor had similar changes in body composition and energy expenditure to noncarriers of the variant in response to prolonged caloric restriction. These results suggest that the presence of the Trp64Arg variant in the [beta ] 3 -adrenoceptor should not be a hindrance to weight reduction.

Thyroid hormone action is an important determinant of energy and glucose metabolism. T4 metabolism is regulated by the deiodinases of which type 2 is expressed in humans in skeletal muscle and brown adipose tissue, where its transcription is stimulated by the β-3 adrenergic pathway. We performed molecular scanning of the human type 2 deiodinase (DIO2) gene and evaluated a novel variant for associations with obesity and insulin resistance, assessing both the main effect and interaction with the Trp64Arg β-3–adrenergic receptor (ADRB3) variant. Molecular scanning of DIO2 in 50 obese Caucasians demonstrated a Thr92Ala variant. Association studies in 972 nondiabetic patients, 135 of whom underwent euglycemic-hyperinsulinemic clamps, showed that subjects with the Thr92Ala variant had lower glucose disposal rate (0.54 ± 0.02 mg · min−1 · kg−1 fat-free mass Ala92 homozygotes vs. 0.44 ± 0.02 Ala92 heterozygotes vs. 0.42 ± 0.04 Thr92 homozygotes, P = 0.0088). Association analysis of the entire group showed significant evidence for a synergistic effect between the Thr92Ala DIO2 and Trp64Arg ADRB3 variants on BMI (both variants 34.3 ± 0.9 kg/m2 vs. neither variant 33.1 ± 0.4 kg/m2, P = 0.04 for interaction). To our knowledge, Thr92Ala is the first description of a missense mutation of DIO2. This variant strongly associates with insulin resistance and, in subjects with the Trp64Arg ADRB3 variant, an increased BMI, suggesting an interaction between these two common gene variants.

Although obesity is often associated with insulin resistance and a cluster of metabolic disturbances, the existence of a subgroup of healthy but obese individuals has been postulated. It is unclear why some obese individuals fail to show traditional risk factors associated with the insulin resistance syndrome despite having a very high accumulation of body fat. To address this issue, we identified and studied a subgroup of metabolically normal but obese (MNO) postmenopausal women to gain insight into potential physiological factors that may protect them against the development of obesity-related comorbidities. We carefully examined the metabolic characteristics of 43 obese, sedentary postmenopausal women (mean ± sd, 58.0± 6.0 yr). Subjects were classified as MNO or as metabolically abnormal obese (MAO) based on an accepted cut-point for insulin sensitivity (measured by the hyperinsulinemic/euglycemic clamp technique). Thereafter, we determined 1) body composition (fat mass and lean body mass), 2) body fat distribution (abdominal visceral and sc adipose tissue areas, midthigh sc adipose tissue and muscle attenuation), 3) plasma lipid-lipoprotein levels, 4) plasma glucose and insulin concentrations, 5) resting blood pressure, 6) peak oxygen consumption, 7) physical activity energy expenditure, and 8) age-related onset of obesity with a questionnaire as potential modulators of differences in the risk profile. We identified 17 MNO subjects who displayed high insulin sensitivity (11.2 ± 2.6 mg/min·kg lean body mass) and 26 MAO subjects with lower insulin sensitivity (5.7 ± 1.1 mg/min·kg lean body mass). Despite comparable total body fatness between groups (45.2 ± 5.3% vs. 44.8 ± 6.6%; P = NS), MNO individuals had 49% less visceral adipose tissue than MAO subjects (141 ± 53 vs. 211 ± 85 cm2; P < 0.01). No difference was noted between groups for abdominal sc adipose tissue (453 ± 126 vs. 442 ± 144 cm2; P = NS), total fat mass (38.1 ± 10.6 vs. 40.0 ± 11.8 kg), muscle attenuation (42.2± 2.6 vs. 43.6 ± 4.8 Houndsfield units), and physical activity energy expenditure (1060 ± 323 vs. 1045 ± 331 Cal/day). MNO subjects had lower fasting plasma glucose and insulin concentrations and lower insulin levels during the oral glucose tolerance test (P values ranging between 0.01–0.001). No difference was observed between groups for 2-h glucose levels and glucose area during the oral glucose tolerance test. MNO subjects showed lower plasma triglycerides and higher high density lipoprotein cholesterol concentrations than MAO individuals (P < 0.01 in both cases). Results from the questionnaire indicated that 48% of the MNO women presented an early onset of obesity ( Our results support the existence of a subgroup of obese but metabolically normal postmenopausal women who display high levels of insulin sensitivity despite having a high accumulation of body fat. This metabolically normal profile is associated with a lower accumulation of visceral adipose tissue and an earlier age-related onset of obesity.

Prior studies suggest that estradiol and progesterone regulate body composition in growing female rats. Because these studies did not consider the confounding effect of changes in food intake, it remains unclear whether ovarian hormones regulate body composition independently of their effects on food intake. We utilized a pair-feeding paradigm to examine the effects of these hormones on body composition. In addition, skeletal muscle protein fractional synthesis rate and adipose tissue lipoprotein lipase activity were measured to examine pathways of substrate deposition into fat and fat-free tissue. Female Sprague-Dawley rats [pubertal: 7–8 wk old; 190 ± 0.5 (SE) g] were separated into four groups: 1) sham-operated (S; n = 8), 2) ovariectomized plus placebo (OVX; n = 8), 3) ovariectomized plus estradiol (OVX+E; n = 8), and 4) ovariectomized plus progesterone (OVX+P; n = 8). All ovariectomized groups were pair-fed to the S group. Body composition was measured using total body electrical conductivity. The relative increase in fat-free mass was greater ( P < 0.01) in the OVX group (31 ± 2%) than in the S (17 ± 2%), OVX+E (18 ± 2%), and OVX+P (22 ± 2%) groups. The fractional synthetic rates of gastrocnemius muscle protein paralleled changes in fat-free mass: OVX had a higher ( P < 0.05) synthesis rate (21 ± 3%/day) than S (12 ± 2%/day), OVX+E (11 ± 2%/day), and OVX+P (8 ± 1%/day) groups. Body fat increased in the S group (31 ± 7%; P < 0.01), whereas the OVX groups lost fat (OVX: −10 ± 7%; OVX+E: −15 ± 7%; OVX+P: −13 ± 7%). No differences in lipoprotein lipase were found. Our results suggest that estradiol and progesterone may regulate the growth of fat and fat-free tissues in female rats. Moreover, ovarian hormones may influence skeletal muscle growth through their effects on skeletal muscle protein synthesis.

Controversy exists regarding the association between the Trp64Arg variant of the beta3-adrenoceptor gene and visceral obesity. The cross-sectional nature of most studies, the modest effect of the variant, and sex or ethnic differences between groups have contributed to discrepancies among investigations. To overcome these confounding factors, we examined the effect of the Trp64Arg variant on total and visceral adipose tissue loss, insulin sensitivity, and cardiovascular disease risk factors in response to weight reduction in obese older women. A total of 24 women (age 57 +/- 4 years), including 1 Trp64Arg homozygote, 10 Trp64Arg heterozygotes, and 13 normal homozygotes, were admitted to a weight reduction program of 13 +/- 3 months, with weight and nutritional intake stabilization established before testing. Total and regional adiposity were measured with dual-energy X-ray absorptiometry and computed tomography, insulin sensitivity was measured by the hyperinsulinemic-euglycemic clamp technique, and a blood lipid profile was obtained. No baseline differences were noted in adiposity measurements, glucose disposal, and lipid profiles among carriers and noncarriers of the variant allele. In response to weight loss, carriers and noncarriers of the Trp64Arg allele had similar reductions in body weight (-16.4 +/- 5.0 vs. -14.1 +/- 6.2 kg, NS) and body fat (-10.0 +/- 5.2 vs. -11.5 +/- 3.9 kg, NS). However, loss of visceral adipose tissue was 43% lower in carriers of the Trp64Arg allele compared with noncarriers (-46 +/- 27 vs. -81 +/- 51 cm2, P = 0.05). Furthermore, there was less improvement in the total cholesterol-to-HDL cholesterol ratio (-0.18 +/- 0.54 vs. -0.72 +/- 0.56, P = 0.04) in carriers compared with noncarriers of the allele. Although glucose disposal improved in both groups, there was no difference in the magnitude of improvement between carriers and noncarriers of the variant allele. In conclusion, older obese women carrying the Trp64Arg beta3-adrenoceptor gene variant have an impaired capacity to lose visceral adipose tissue in response to prolonged caloric restriction. Despite these genetic differences in loss of intraabdominal adipose tissue, improvement in glucose disposal was similar between groups.

Older obese postmenopausal women have an increased risk for type 2 diabetes and cardiovascular disease. Increased abdominal obesity may contribute to these comorbidities. There is considerable controversy, however, regarding the effects of visceral adipose tissue as a singular predictor of insulin resistance compared to the other constituents of adiposity. To address this issue, we examined the independent association of regional adiposity and total fat mass with glucose disposal in obese older postmenopausal women. A secondary objective examined the association between glucose disposal with markers of skeletal muscle fat content (muscle attenuation) and physical activity levels. We studied 44 healthy obese postmenopausal women between 50 and 71 yr of age (mean ± sd, 56.5 ± 5.3 yr). The rate of glucose disposal was measured using the euglycemic/hyperinsulinemic clamp technique. Visceral and sc adipose tissue areas and midthigh muscle attenuation were measured from computed tomography. Fat mass and lean body mass were estimated from dual energy x-ray absorptiometry. Peak VO2 was measured from a treadmill test to volitional fatigue. Physical activity energy expenditure was measured from indirect calorimetry and doubly labeled water. Pearson correlations indicated that glucose disposal was inversely related to visceral adipose tissue area (r = −0.40; P < 0.01), but not to sc adipose tissue area (r = 0.17), total fat mass (r = 0.05), midthigh muscle attenuation (r = 0.01), peak VO2 (r = −0.22), or physical activity energy expenditure (r = −0.01). The significant association persisted after adjusting visceral adipose tissue for fat mass and abdominal sc adipose tissue levels (r = −0.45; P < 0.005; in both cases). Additional analyses matched two groups of women for fat mass, but with different visceral adipose tissue levels. Results showed that obese women with high visceral adipose tissue levels (283 ± 59 vs. 137 ± 24 cm2; P < 0.0001) had a lower glucose disposal per kg lean body mass compared to those with low visceral adipose tissue levels (0.44 ± 0.14 vs. 0.66 ± 0.28 mmol/kg·min; P < 0.05). Visceral adipose tissue is an important and independent predictor of glucose disposal, whereas markers of skeletal muscle fat content or physical activity exhibit little association in obese postmenopausal women.

We examined the effects of a 6-month randomized program of endurance training (n = 14), resistance training (n = 17), or control conditions (n = 20) on insulin sensitivity in nonobese, younger women (18–35 yr). To examine the possible mechanism(s) related to alterations in insulin sensitivity, we measured body composition, regional adiposity, and skeletal muscle characteristics with computed tomography. We observed no changes in total body fat, sc abdominal adipose tissue, or visceral adipose tissue with endurance or resistance training. Insulin sensitivity, however, increased with endurance training (pre, 421 ± 107; post, 490 ± 133 mg/min; P < 0.05) and resistance training (pre, 382± 87; post, 417 ± 89 mg/min; P = 0.06). When the glucose disposal rate was expressed per kg fat-free mass (FFM), the improved insulin sensitivity persisted in endurance-trained (pre, 10.5 ± 2.7; post, 12.1 ± 3.3 mg/min·kg FFM; P < 0.05), but not in resistance-trained (pre, 9.7 ± 1.9; post, 10.2 ± 1.8 mg/min·kg FFM; P = NS) women. Muscle attenuation ratios increased (P < 0.05) in both endurance- and resistance-trained individuals, but this was not related to changes in insulin sensitivity. Moreover, the change in insulin sensitivity was not related to the increased maximum aerobic capacity in endurance-trained women (r = 0.24; P = NS). We suggest that both endurance and resistance training improve glucose disposal, although by different mechanisms, in young women. An increase in the amount of FFM from resistance training contributes to increased glucose disposal probably from a mass effect, without altering the intrinsic capacity of the muscle to respond to insulin. On the other hand, endurance training enhances glucose disposal independent of changes in FFM or maximum aerobic capacity, suggestive of an intrinsic change in the muscle to metabolize glucose. We conclude that enhanced glucose uptake after physical training in young women occurs with and without changes in FFM and body composition.

BACKGROUND Cardiac rehabilitation programs have evolved to become secondary prevention centers. However, the independent effect of exercise alone on coronary risk factors and body composition in patients with coronary artery disease has not been well studied. OBJECTIVE The aim of this study was to determine the effect of exercise training alone, without modification of dietary intake, on coronary risk factors and body composition in a coronary population. METHODS The authors studied 82 coronary patients (23 females and 59 males) aged 61.2 +/- 12.2 years (mean +/- SD) before and after a 3-month exercise training program. Outcome variables included serum lipid values, glucose, insulin, body composition, body fat distribution, macronutrient intake, and peak aerobic capacity. RESULTS Neither male nor female patients experienced a significant overall improvement in plasma cholesterol, low-density lipoprotein (LDL)-cholesterol, triglycerides, glucose, or insulin levels after the 3-month exercise training program. Dietary macronutrient intake was unaltered during the study period. Peak aerobic capacity increased by 3.4 +/- 4.7 ml/kg/min (17%, P < 0.0001) and high-density lipoprotein (HDL)-cholesterol increased from 38 +/- 10 to 41 +/- 11 mg/dL (8%, P < 0.001) after the rehabilitation program. Patients with baseline triglyceride levels over 200 mg/dL experienced a 22% decrease (from 374 +/- 205 to 293 +/- 190 mg/dL; P < 0.05) after conditioning. Patients with baseline HDL-cholesterol levels under 35 mg/dL also improved overall by 17% (from 29 +/- 3 to 34 +/- 5 mg/dL; P < 0.0001). Exercise-induced changes in plasma HDL-cholesterol were more related to changes in body composition and/or body fat distribution, rather than changes in peak aerobic capacity. CONCLUSION Exercise conditioning alone resulted in relatively modest risk factor improvements in coronary patients after 3 months. High-density lipoprotein cholesterol measures increased by 3 +/- 8 mg/dL (8%). Patients with baseline triglyceride elevations experienced a 22% decrease. On the other hand, there were no overall effects on body weight, total cholesterol, LDL-cholesterol, triglycerides, glucose, or insulin levels. For most patients, exercise effects were minimal and nutritional and medical therapy will need to be used more aggressively to attain nationally recognized risk factor goals.

The age-related loss of fat-free mass (FFM) is accelerated in women during the middle-age years and continues at an increased rate throughout the postmenopausal period. Because protein is the primary structural component of fat-free tissue, changes in FFM are largely due to alterations in protein metabolism. Knowledge of the hormonal and physiological correlates of protein metabolism in middle-aged women, therefore, has important implications for understanding the mechanisms underlying changes in FFM. We measured leucine kinetics (expressed relative to FFM: μmol/kg FFM·h) in 46 middle-aged, premenopausal women (mean ± sd, 47 ± 3 yr) after an overnight fast (i.e. basal) and during euglycemic hyperinsulinemia (40 mU/m2·min) using a 5.5-h infusion of[ 1-13C]leucine. Additionally, we measured insulin-stimulated glucose disposal by euglycemic hyperinsulinemic clamp, body composition by dual energy x-ray absorptiometry, abdominal fat distribution by computed tomography, and hormone levels by RIA as possible cor...

The objective of this study was to examine the importance of cardiorespiratory fitness vs. physical activity energy expenditure on selected cardiovascular disease risk factors in older individuals. One hundred and seventeen older individuals, 53 men (68 ± 9 yr) and 63 women (67 ± 7 yr), participated in the study. This cohort was divided into 4 groups: 1) high cardiorespiratory fitness and high physical activity, 2) high cardiorespiratory fitness and low physical activity, 3) low cardiorespiratory fitness and high physical activity, and 4) low cardiorespiratory fitness and low physical activity. Cardiorespiratory fitness (VO2max) was determined from a graded exercise test, physical activity energy expenditure was measured by doubly labeled water and indirect calorimetry, body composition was determined by dual energy x-ray absorptiometry, and dietary practices were determined by a 3-day recall. Cardiorespiratory fitness exerted greater effects on the cardiovascular disease risk profile than physical activity. That is, older individuals with higher levels of cardiorespiratory fitness, regardless of their physical activity levels, showed lower levels of fasting insulin (P < 0.01), triglycerides (P < 0.05), total cholesterol (P < 0.05), total to high density lipoprotein cholesterol ratio (P < 0.05), low density lipoprotein (P < 0.05), and lower waist circumference (P < 0.01). Moreover, individuals with a high cardiorespiratory fitness but low physical activity energy expenditure displayed a more favorable cardiovascular disease risk profile than individuals with low cardiorespiratory fitness and high physical activity energy expenditure. The results suggest that higher levels of cardiorespiratory fitness have greater cardioprotective effects than higher levels of free living physical activity in older individuals. Although these findings do not discount the health benefits of being physically active, it is possible that greater emphasis should be placed on aerobic exercise to increase cardiorespiratory fitness in the elderly.

Obesity is an independent risk factor for the development of coronary artery disease (CAD). Obesity also increases risk for CAD indirectly through its association with insulin resistance, hyperlipidemia, and hypertension. An increased accumulation of fat in the intraabdominal cavity, termed visceral adiposity, is highly correlated with an adverse coronary risk profile. In patients at risk for coronary artery disease, the treatment of obesity results in an improved coronary risk profile. The prevalence of obesity is extremely high in coronary populations, yet the effect of weight loss on cardiovascular outcomes in CAD patients has received relatively little attention. Observational studies in the cardiac rehabilitation setting showed that patients who lose weight and exercise show an improvement in coronary risk profile. Further research is needed to better define the clinical effectiveness of weight loss programs and their benefits in coronary patients.

Few studies have investigated the influence of body composition, abdominal obesity, age and fitness on coronary risk factors in populations of patients with coronary heart disease (CHD). We investigated whether abdominal obesity or generalized adiposity is a better predictor of cardiovascular risk in men with coronary artery disease (CAD), and the effects of exercise training on coronary risk factors in younger and older patients with CAD.The study population consisted of 81 male patients aged 33-83 years (mean +/- SD 60.0 +/- 13.3 years) with established CAD. We studied the relationships among body composition, body fat distribution, dietary intake, peak aerobic capacity, lipid concentrations, and plasma glucose and insulin concentrations. We subsequently measured the influence of exercise training on these components.The study population was characterized by a high prevalence of obesity, particularly in younger patients. Body mass index, rather than body fat distribution, was the best anthropometric predictor of plasma triglyceride concentrations (r2 = 0.11, P0.05) and cholesterol/high-density lipoprotein cholesterol (HDL-C) ratio (r2 = 0.13, P0.01). Body weight, rather than body fat distribution, was the best predictor of plasma HDL-C concentration (r2 = 0.14, P0.01) and fasting glucose concentrations (r2 = 0.10, P0.05). Fat mass was the best anthropometric predictor of fasting plasma insulin concentrations (r2 = 0.38, P0.0001) and for the glucose-insulin ratio (r2 = 0.39, P0.0001) in men with CAD. Younger patients tended to have greater improvements in HDL-C concentrations and the cholesterol:HDL-C ratio than did older individuals, as a result of exercise training.In men with CAD, general measures of obesity, such as body weight, body mass index, and fat mass are better predictors of coronary risk factors than body fat distribution. Younger and older men with CAD experienced similar improvements in body composition and body fat distribution after an exercise training program.

Preliminary studies suggest that the menopause transition is associated with deleterious changes in body composition and abdominal fat distribution. Limitations of the methodology used in these studies, however, render their conclusions controversial. Thus, the present study used radiologic imaging techniques to examine the effect of menopausal status on body composition and abdominal fat distribution.Cross-sectional.Fifty-three healthy, middle-aged, premenopausal women (mean+/-SD; 47+/-3 y) and 28 early-postmenopausal women (51+/-4 y).Total and regional body composition by dual energy X-ray absorptiometry and abdominal fat distribution by computed tomography.No differences in total body fat-free mass or appendicular skeletal muscle mass were noted between groups. In contrast, total body fat mass was 28% higher (23+/-7 vs 18+/-7 kg) and percentage fat 17% higher (35+/-6 vs 30+/-9%; both P0.01) in postmenopausal women compared with premenopausal women. Postmenopausal women had a 49% greater intra-abdominal (88+/-32 vs 59+/-32 cm2; P0.01) and a 22% greater abdominal subcutaneous fat area (277+/-93 vs 227+/-108 cm2; P0.05) compared to premenopausal women. The menopause-related difference in intra-abdominal fat persisted (P0.05) after statistical adjustment for age and total body fat mass, whereas no difference in abdominal subcutaneous fat was noted. A similar pattern of differences in total and abdominal adiposity was noted in sub-samples of pre- and postmenopausal women matched for age or fat mass.Our data suggest that early-postmenopausal status is associated with a preferential increase in intra-abdominal fat that is independent of age and total body fat mass. International Journal of Obesity (2000) 24, 226-231

Alzheimer disease is one of the leading causes of death among older individuals. Unexplained weight loss and cachexia are frequent clinical findings in patients with Alzheimer disease. Thus, it has been postulated that Alzheimer disease may be associated with dysfunction in body weight regulation. This brief review examines the interrelations among energy intake, energy expenditure, and body composition in Alzheimer disease. We explored whether abnormally high daily energy expenditures, low energy intakes, or both contribute to unexplained weight loss and a decline in nutritional status. Specifically, we considered studies that examined energy intake, body composition, and daily energy expenditure and its components. The application of doubly labeled water and indirect calorimetry to understand the etiology of wasting has increased our knowledge regarding the relation among energy expenditure, physical activity levels, and body composition in Alzheimer disease patients. Although the number of studies are limited, results do not support the notion that a hypermetabolic state contributes to unexplained weight loss in Alzheimer disease, even in cachectic patients. Recent findings are presented suggesting an association between abnormally elevated levels of physical activity energy expenditure and elevated appendicular skeletal muscle mass and energy intake in Alzheimer disease patients. Clinical strategies aimed at developing lifestyle and dietary interventions to maintain adequate energy intake, restore energy balance, and maintain skeletal muscle mass should be a future area of investigation in Alzheimer disease research.

Objective: To examine the relation between insulin sensitivity and total and regional body fat in nonobese postmenopausal women. Design: Cross-sectional study. Setting: A clinical research center. Patient(s): Twenty-seven women in the early postmenopausal period, with a mean (±SD) age of 50.8 ± 4.1 years, who had had their last menstrual period 6 months to 3 years before the study. None were taking hormone replacement therapy, and all had an FSH level of >35 mIU/mL, a body mass index of 2 , and a waist circumference of Intervention(s): Computed tomography scans at the L4–5 vertebral disk space, dual-photon x-ray absorptiometry scans, and euglycemic hyperinsulinemic clamps were performed. Main Outcome Measure(s): Intraabdominal fat, subcutaneous abdominal fat, sagittal diameter, total body fat, percent body fat, and insulin sensitivity. Result(s): The natural log of insulin sensitivity correlated significantly with intraabdominal fat ( r = −.39), subcutaneous fat ( r = −.43), and sagittal diameter ( r = −.48). After adjusting for total fat, sagittal diameter remained significantly related to insulin sensitivity. Conclusion(s): Central abdominal fat is inversely and independently related to insulin sensitivity after adjusting for total fat in women in the early postmenopausal period. Efforts to reduce either subcutaneous abdominal fat or intraabdominal fat should be helpful in reducing the risk of noninsulin-dependent diabetes mellitus in postmenopausal women.

There is considerable controversy regarding factors regulating free-living physical activity energy expenditure (PAEE) in older individuals. This component is highly variable, is difficult to accurately assess, and reflects both volitional and nonvolitional activities. We examined the association between maximal aerobic fitness (peak VO2) and free-living PAEE in older individuals. One hundred and eighty healthy older patients (96 females and 84 males) between 45–90 yr of age were studied. Total energy expenditure was measured from doubly labeled water. PAEE was calculated as the difference between total energy expenditure, resting metabolic rate, and estimated thermic effect of a meal. Peak VO2 was assessed from an exercise test to volitional fatigue. Fat mass and fat-free mass were assessed from dual energy x-ray absorptiometry. After correction for age, fat mass, and fat-free mass, significant correlations were observed between peak VO2 and PAEE for older males (r = 0.42; P < 0.0001) and females (r = 0....

An understanding of the hormonal and physiological correlates of energy expenditure and substrate oxidation in middle-aged women will increase our knowledge of factors that promote changes in energy balance and adiposity. We measured resting and postprandial energy expenditure and substrate oxidation in 59 middle-aged, premenopausal women (mean+/-sD age, 47+/-2 yr) to examine the hormonal and physiological correlates of energy and substrate metabolism. Energy expenditure and substrate oxidation were measured at rest using indirect calorimetry and urinary nitrogen excretion and for 180 min after the ingestion of a liquid meal (10 kcal/kg fat-free mass; 410+/-44 Cal). Fasting hormone levels were measured by RIA, glucose tolerance was determined by a 75-g oral glucose tolerance test, body composition was measured by dual energy x-ray absorptiometry, and peak aerobic capacity was determined by a treadmill test. Using stepwise regression analysis, we found that resting energy expenditure was predicted by fat-free mass and serum leptin concentration (r2 = 66%; P < 0.01), fat oxidation was predicted by resting energy expenditure (r2 = 17%; P < 0.01), and carbohydrate oxidation was predicted by serum leptin and appendicular skeletal muscle mass (r2 = 21%;P < 0.01). Novariables were related to postprandial energy expenditure or substrate oxidation. We conclude that in middle-aged, premenopausal women, variation in resting energy expenditure and substrate oxidation is primarily explained by fat-free mass and serum leptin levels. Thus, changes in metabolically active tissue mass or leptin concentration may partially contribute to changes in resting energy expenditure or substrate oxidation in middle-aged women.

We examined the hypothesis that postmenopausal women with the beta3-adrenoceptor gene variant (Trp64Arg) have reduced total daily energy expenditure (TEE), altered free fatty acid kinetics, and increased intra-abdominal fat. A secondary objective was to examine whether the obese state masks the effect of the variant on resting metabolic rate (RMR). There were 23 obese heterozygous women with the genetic variant (age 58 +/- 6 years; BMI 36 +/- 7 kg/m2) who were compared with 19 homozygous obese women with the normal allele (age 56 +/- 4 years; BMI 36 +/- 3 kg/m2). Daily energy expenditure was determined from doubly labeled water and indirect calorimetry, lipolysis from infusion of [1-13C]palmitate, and body fat distribution from computed tomography. No significant differences were found in TEE, RMR, energy expenditure of physical activity, the thermic effect of a meal, fat oxidation as estimated by fasting and postprandial respiratory quotients (RQs), or rate of lipolysis. Similarly, no difference was found in visceral adipose tissue and abdominal subcutaneous fat areas. When RMR was compared between obese (n = 23) and never-obese women with the Trp64Arg variant (n = 16), we found a 317 kcal/day lower RMR in never-obese women after controlling for fat mass, fat-free mass, and age (P < 0.0017). These results do not support the hypothesis that already obese women with the Trp64Arg polymorphism of the beta3-adrenergic receptor gene have lower daily energy expenditure, altered lipolysis, and increased abdominal obesity. On the other hand, the lower RMR in never-obese women suggests that the obese state may mask a moderate effect of the Trp64Arg variant on energy expenditure. Although these results need to be confirmed in other populations, the obese state may have been a confounding factor in previous studies of the beta3-adrenoceptor Trp64Arg variant and energy expenditure.

The authors determined the frequency and effectiveness of pharmacologic lipid lowering, guided by the recommendations of the National Cholesterol Education Program (NCEP) before and after institution of a systematic lipid assessment performed at the time of the cardiac rehabilitation entry evaluation.The systematic lipid evaluation included a full lipid profile and a dietary evaluation at which time an active approach to pharmacologic lipid therapy was taken. Therapy was guided by the NCEP guidelines, with the collaboration of the referring physician. The frequency of lipid therapy change (starting or changing therapy) from the baseline evaluation to a 3-month follow-up visit was the primary study outcome variable. The control group consisted of 51 patients with coronary heart disease (CHD) seen in 1995 at cardiac rehabilitation, who agreed to have their serum lipids measured in a double-blinded fashion. There was no systematic lipid lowering intervention. The intervention group consisted of 187 patients with CHD who participated in cardiac rehabilitation in 1996 to 1997.At baseline, a similar percentage of patients in each group were on lipid lowering therapy: 38% (19/51) in controls versus 35% (65/187) in intervention patients. Among patients with a baseline low-density lipoprotein (LDL) cholesterol ofor = 130 mg/dL, therapy was modified in 18% (4/22) of control patients compared with 52% (35/68) of intervention patients (P0.05). Among patients with a baseline LDL cholesterol ofor = 160, therapy was altered in 22% (2/9) control patients compared with 72% (18/25) intervention patients (P0.01). In both risk strata ofor = 130 mg/dL andor = 160 mg/dL, LDL cholesterol measures were lowered to a greater degree in the intervention group.The performance of a systematic lipid review at the time of cardiac rehabilitation entry, with an active stance toward pharmacologic therapy, results in a threefold increase in pharmacologic modifications and lower LDL cholesterol values for cardiac rehabilitation participants.

Wasting and cachexia are significant problems in the elderly that increase mortality and morbidity. It is presently unclear as to the physiological mechanism underlying unexplained weight loss. We examine heart failure as a physiological model to demonstrate the importance of measuring several physiological outcome variables that have increased our understanding of wasting and cachexia in the elderly. These include the assessment of: energy expenditure, body composition, physical activity and exercise tolerance. We review recent data that has assessed energy expenditure in free-living heart failure patients using stable isotope methodology (doubly labeled water). Preliminary results show low levels of daily energy expenditure in heart failure patients due to extremely low levels of physical activity. Thus, a hypermetabolic state in free-living heart failure patients is not supported by these findings. The low level of physical activity is likely a consequence of their reduced exercise capacity and contributes to their skeletal muscle atrophy. This concept is support by the relationship between peak VO 2 and muscle mass (r = 0.92; P < 0.01), as measured from dual energy x-ray absorptiometry. An understanding of the physiological factors influencing energy dysregulation and low exercise capacity may help guide future therapeutic interventions to restore energy balance and increase functional independence in patients with chronic heart failure.

There is controversy regarding the role of the Trp64Arg variant of the beta3-adrenergic receptor (beta3AR) gene in the pathogenesis of insulin resistance. The modest effect of the variant as well as differences in study design, gender, age, and genetic background may contribute to divergent results among investigations. Insulin sensitivity (euglycemic clamp and tracers) was measured in 13 obese women (57 +/- 6 yr old) heterozygous for the beta3AR variant and in 14 women (57 +/- 4 yr old) homozygous for the normal gene. Groups were matched for age, body composition, intraabdominal fat, sc abdominal fat, physical activity level, and aerobic capacity. Exogenous glucose infusion during the clamp was significantly lower (P = 0.03) in beta3AR heterozygotes (241 +/- 135 mg/min) vs. normal homozygotes (379 +/- 172 mg/min). Basal endogenous glucose production was not different (P = 0.20) between heterozygotes (175 +/- 27 mg/min) and normal homozygotes (164 +/- 14 mg/min). Endogenous glucose production during hyperinsulinemia was also not different (P = 0.22) between heterozygotes (77 +/- 57 mg/min) and normal homozygotes (56 +/- 16 mg/min). Total glucose disposal adjusted for residual endogenous glucose production was lower (P = 0.049) for heterozygotes (320 +/- 111 mg/min) than for normal homozygotes (441 +/- 183 mg/min). Our results suggest that obese postmenopausal women who are heterozygous for the Trp64Arg variant in the beta3AR gene have greater insulin resistance than age-, body composition-, and physical activity-matched women homozygous for the normal gene.

Objective: To examine age-related differences in blood pressure, heart rate, behavioral mood state and norepinephrine kinetics after caffeine ingestion in younger and older men. Design: Placebo-controlled, double-blind study. Setting: General Clinical Research Center, University of Vermont. Subjects: 10 older (O) (65–80 y) and 10 younger (Y) (19–26 y) healthy men who were moderate consumers of caffeine (Y=126±30 mg/d; O=160±44 mg/d:NS; mean±s.e.m.). Intervention: All volunteers were characterized for fasting plasma glucose, insulin and caffeine levels, body composition, anthropometry, physical activity, and energy intake. Before and after placebo and caffeine ingestion (5 mg/kg fat-free mass) test days, the following variables were measured in all subjects: heart rate, blood pressure, mood state, and norepinephrine concentrations (NEconc), appearance (NEapp) and clearance (NEcl). Main outcome measures: Systolic and diastolic blood pressure, heart rate, mood state, and norepinephrine kinetic responses to placebo and caffeine ingestion. Results: Following caffeine ingestion, plasma caffeine levels were similar in Y and O men. Systolic (SBP) and diastolic (DBP) blood pressure increased significantly (P

To examine the interrelations among appendicular skeletal muscle mass and physical activity, energy intake, and cognitive status in free-living patients with AD.Increasing disease severity in AD patients may contribute to poor nutritional status and loss of skeletal muscle mass. This may lead to impaired physical function and loss of functional independence.Participants in our study were 30 noninstitutionalized AD patients (74 +/- 8 years) and 30 healthy age- and body mass index-matched control subjects (73 +/- 7 years). We measured appendicular skeletal muscle mass by dual-energy X-ray absorptiometry, energy expenditure by doubly labeled water, and energy intake by food diaries.As expected, the AD group had lower Mini-Mental State Examination scores than the control subjects (p0.05). No differences in energy intake or energy expenditure and its components were noted between the groups. Higher levels of appendicular muscle mass in AD patients were associated with increased energy expenditure of physical activity (r = 0.52, p0.01) and daily energy intake (r = 0.49, p = 0.01). Cognitive status was not related to appendicular muscle mass, daily energy intake, or energy expenditure of physical activity in AD patients.Higher levels of physical activity and energy intake are associated with higher appendicular skeletal muscle mass in AD patients. Nutritional and physical activity interventions may represent practical and inexpensive strategies in their therapeutic management.

The sympathetic nervous system participates in the regulation of carbohydrate, lipid, and energy metabolism, and has been implicated in the pathogenesis of hypertension and obesity. Increased sympathetic nervous system activity with age may alter disease risk and contribute to the development of certain chronic diseases. Thus, we examined possible determinants of sympathetic nervous system activity in older normotensive women from infusions of tritiated norepinephrine (NE) to estimate rates of norepinephrine appearance and clearance. A secondary aim was to examine the association between norepinephrine kinetics and mean supine arterial blood pressure. Twenty-two older women (65.7 +/- 5.7 years) were characterized for resting NE kinetics, body composition, body fat distribution, peak aerobic capacity, leisure time physical activity energy expenditure (LTA), dietary carbohydrates, and daily energy intake. Analysis of univariate correlations revealed that only the LTA was significantly correlated with plasma NE appearance (r = 0.54, p < 0.01). Stepwise regression analysis identified LTA as the only significant predictor of plasma NE appearance rate with a total R2 = 0.29. The waist-to-hip ratio was selected as the only significant predictor of mean arterial blood pressure with an R2 = 0.30. When forced into the model, plasma NE appearance explained only 1% of the unique variance in mean arterial blood pressure. In summary, we found that: (1) higher levels of physical activity are related to higher plasma NE appearance in older women; (2) greater central body fatness is an independent predictor of mean arterial blood pressure; and (3) plasma NE appearance rate is a minor contributor to variation in mean arterial blood pressure in older, normotensive women.

OBJECTIVE: In the postmenopausal years, women develop a central pattern of fat distribution and an increased risk of developing cardiovascular disease (CVD). The possibility that these events are related has not been extensively investigated. The object of the present study was to test the hypotheses that, 1) menopause-related differences in lipids are associated with greater estimated intra-abdominal adiposity, and 2) the relationship between individual adipose depots and plasma lipids differs with menopausal status. DESIGN: Cross-sectional. SUBJECTS: 141 healthy pre- and postmenopausal women aged 35 ‐ 65 y. MEASUREMENTS: Total body fat by hydrodensitometry was used as an index of whole-body adiposity, the sum of five central skinfold measurements as an index of subcutaneous upper-body adiposity, and estimated intra-abdominal adipose tissue (IAF) as an index of visceral adiposity. Fasting plasma concentrations of total cholesterol (total-C), highand low-density-lipoprotein cholesterol (HDL-C, LDL-C), and triglycerides were used as indices of CVD risk. RESULTS: Postmenopausal women had greater total body fat (P< 0.001), summed central skinfolds (P< 0.01), estimated IAF (P< 0.001), higher plasma concentrations of total-C (P< 0.001), LDL-C (P< 0.001) and triglycerides (P< 0.001), than premenopausal women. The relationship between central skinfolds and LDL-C differed with menopausal status, being significant in pre- but not postmenopausal women. Adjustment for estimated IAF with analysis of covariance decreased menopause-related differences in levels of total-C, LDL-C and triglycerides by approx 40 ‐ 70%. CONCLUSION: These observations suggest that, 1) menopause-related changes in IAF may adversely affect the plasma lipid profile, and 2) menopausal status affects the relationship between central subcutaneous fat and LDL-C. Studies with measured IAF are needed to confirm present results.

We examined daily energy requirements and determinants of physical activity in older, free-living African-American women (n = 37; age, 64 ± 8 yr) and men (n = 28; age, 64 ± 7 yr). Total daily energy expenditure and its components [i.e. resting metabolic rate (RMR) and physical activity energy expenditure] were determined using doubly labeled water and indirect calorimetry. Body composition from dual energy x-ray absorptiometry, maximal oxygen consumption from a graded treadmill test, and leisure time physical activity from a structured interview were determined. Total daily energy expenditure adjusted for body composition was lower (P < 0.05) for women (2198 ± 621 kcal/d) than for men (2633 ± 669 kcal/d) due to a lower RMR (1431 ± 240 vs. 1576 ± 259 kcal/d; P = 0.07) and physical activity energy expenditure (548 ± 559 vs. 794 ± 603 kcal/d; P = 0.19), respectively. The physical activity level ratio (i.e. total daily energy expenditure/RMR) was not different from Food and Agriculture Organization/World Heal...

In addition to being associated with termination of reproductive life in women, the menopause coincides with an increase in several comorbidities including cardiovascular disease. This increase in the prevalence of cardiovascular disease in the postmenopausal years has been partially attributed to adverse effects of estrogen deficiency on plasma lipid-lipoprotein levels and on the cardiovascular system, although other factors are contributing. Central body fatness and insulin resistance are components of a cluster of metabolic abnormalities which also increases the risk of cardiovascular disease. This review summarizes studies that have examined the effects of the menopause transition and of estrogen-replacement therapy on central body fatness and insulin resistance. Review of cross-sectional studies suggests that the menopause transition is associated with an increase in abdominal and visceral adipose tissue accumulation, as measured either with dual X-ray absorptiometry or computed tomography. These results appear to be independent of the aging process and total body fatness. In general, cross-sectional studies using circumference measurements did not find any significant effect of the menopause. Longitudinal studies also support that accumulation of central body fatness accelerates with menopause. The effects of the menopause on insulin resistance appear to be moderate, if any, although available studies are clearly insufficient to draw firm conclusions. The majority of interventional studies support the notion that hormone-replacement therapy attenuates the accumulation of central fat in postmenopausal women, compared with control or placebo-treated women. Retrospective comparisons of hormone users and nonusers also support a protective effect of hormone replacement on fat distribution. Moderate effects of estrogen therapy were found on insulin resistance in postmenopausal women, although long-term, controlled trials using accurate measurements of insulin sensitivity are lacking. Treatment with progestins exerts moderate deleterious effects on insulin sensitivity, which may be attributable to the partial androgenicity of progestins used. It is concluded that part of the increased incidence of cardiovascular disease in postmenopausal women may be attributable to increased central body fatness. Therapies aiming at preventing these changes in fat distribution such as hormone-replacement therapy, diet or exercise are likely to provide long-term cardiovascular and metabolic benefits for women's health.

Low rates of daily energy expenditure, increased energy intake, or a combination of both contribute to obesity in African-Americans. We examined whether African-Americans have lower rates of free-living daily energy expenditure than Caucasians. One hundred sixty-four (>55 yr) volunteers (37 African-American women, 52 Caucasian women, 28 African-American men, and 47 Caucasian men) were characterized for total daily energy expenditure, resting metabolic rate, and physical activity energy expenditure from the doubly labeled water method and indirect calorimetry. Absolute total daily energy expenditure was lower in women than men but was not different between African-Americans and Caucasians. However, we found race and gender differences in total daily energy expenditure after controlling for differences in fat-free mass. Total daily energy expenditure was 10% lower ( P < 0.01) in African-Americans compared with Caucasians due to a 5% lower resting metabolic rate ( P < 0.01) and 19% lower physical activity energy expenditure ( P = 0.08). Moreover, total daily energy expenditure was 16% lower ( P < 0.01) in women compared with men due to a 6% lower resting metabolic rate ( P = 0.09) and a 37% lower physical activity energy expenditure ( P = 0.06). Low rates of energy expenditure may be a predisposing factor for obesity, particularly in African-American women.

We determined the contribution of body fat distribution, peak VO2, fat mass, and dietary intake to variation in plasma lipids in elderly individuals. Volunteers were a healthy cohort of older Caucasian women (n = 75, mean age +/- SD, 72 +/- 5 years) and older men (n = 101, 72 +/- 5 years). We determined fat mass from underwater weighing, fat patterning from waist circumference, as well as peripheral and truncal skinfolds, exercise capacity from peak VO2, and dietary intake from three-day food diaries. Plasma lipid levels were measured in the fasting state and included total cholesterol, high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), and fasting triglycerides. Older women weighted less than older men, but had higher fat mass, truncal, and peripheral skinfolds. Waist circumference and peak VO2 were lower in older women than older men. Older women had higher total cholesterol (217 +/- 31 vs. 197 +/- 30; p0.01), HDL-C (54 +/- 12 vs. 49 +/- 14; p0.05), and LDL-C (133 +/- 26 vs. 121 +/- 27; p0.01) when compared with older men. No gender differences were noted in fasting triglycerides. Truncal skinfolds were the best predictor of plasma lipids in older men, accounting for between 9% and 30% (r2) of the variation in plasma lipids. Similarly, in older women, central markers of fatness (i.e., waist circumference and truncal skinfolds) were the best predictors of plasma lipids (r2 = 3% to 24%). Total fat mass, peak VO2 and dietary intake were not independent predictors of plasma lipids in older men and women. Indices of central body fatness, rather than total fat mass, peak VO2 or dietary intake are stronger predictors of plasma lipids in healthy older men and women.

Recent research suggests that leptin may control body weight by regulating energy expenditure and energy intake in mice. To explore the possible role of leptin in the regulation of energy expenditure in humans, we used doubly-labeled water methodology to determine whether fasting plasma leptin concentrations were related to total daily energy expenditure (TEE) and its components, resting energy expenditure (REE) and physical activity energy expenditure (PAEE), in free-living older African-American men (n = 21) and women (n = 25). Plasma leptin concentrations were higher in women than men, even after the adjustment for differences in fat mass (28 ± 3 ng/ml for women vs. 17 ± 3 ng/ml for men; P < 0.01). The logarithm of plasma leptin concentrations correlated with fat mass in both women (r = 0.80) and men (r = 0.78) (P < 0.0001). After statistical adjustment for sex differences in fat-free mass and fat mass, women had lower TEE (22%) and REE (15%) (P < 0.01) and a trend (P = 0.08) toward lower PAEE, compared with men. After controlling for the effects of fat-free mass on energy expenditure, plasma leptin concentrations were related to REE (r = 0.68, P < 0.001) and tended to be related to TEE (r = 0.37, P = 0.07) in African-American women but not men (r = 0.18 and −0.03, respectively). Plasma leptin concentrations were not related to PAEE in either men or women. These results suggest that leptin may contribute to the regulation of TEE in older African-American women through its effects on resting energy metabolism, but the role of leptin in the regulation of energy expenditure is less apparent in older African-American men.

Leptin, the protein encoded by the obese gene, is a newly described hormone implicated in the regulation of energy balance. To examine the possible role of leptin in the energy dysregulation that frequently accompanies chronic heart failure, we examined plasma leptin concentrations and energy expenditure in 18 heart failure patients (aged 71 ± 6 years) and 46 healthy elderly controls (66 ± 6 years). Plasma leptin concentrations were measured by radioimmunoassay, daily energy expenditure by doubly labeled water, and body composition by dual-energy x-ray absorptiometry. Fat mass was lower (P < .01) in heart failure patients compared with healthy controls, whereas fat-free mass did not differ between groups. Plasma leptin concentrations were not different between heart failure patients and healthy controls (5.1 ± 4.2 v 6.8 ± 4.4 pg/mL) and remained similar after statistical control for fat mass (6.0 ± 3.1 v 7.1 ± 3.2 pg/mL). Plasma leptin was related to fat mass in heart failure patients (r = .92, P < .01) and healthy controls (r = .69, P < .01). Free-living daily and physical-activity energy expenditures were lower (P < .01) in heart failure patients compared with healthy controls. Plasma leptin concentrations were related to both daily (r = .67, P < .01) and resting (r = .67, P < .01) energy expenditure in heart failure patients, but not in healthy controls (r = .09 and r = .33, respectively). In conclusion, we found an association between plasma leptin concentrations and energy expenditure in heart failure patients, but not in healthy controls. Thus, leptin may participate in the regulation of energy expenditure and body energy stores in heart failure patients.

Weight loss is common in Alzheimer's disease (AD), but its pathogenesis is poorly understood. It is unclear whether an elevated daily energy expenditure contributes to the weight loss. We tested the hypothesis that daily energy expenditure is higher in AD patients compared to healthy elderly. Thirty AD (73 +/- 8 years; Mini-Mental State Examination score: 16 +/- 8) and 103 healthy elderly (69 +/- 7 years) were characterized for daily energy expenditure and its components (resting and free-living physical activity energy expenditure) from doubly labeled water and indirect calorimetry. Fat-free mass and fat mass were measured from dual energy X-ray absorptiometry. Fat-free mass tended to be lower in AD patients (45 +/- 9 kg) versus healthy elderly (49 +/- 10 kg; p = 0.07), whereas no differences were noted in fat mass between groups. Daily energy expenditure was 14% lower in AD (1901 +/- 517 kcal/d) compared to healthy elderly (2213 +/- 513 kcal/d; p0.001), due to lower resting (1287 +/- 227 versus 1418 +/- 246 kcal/d; p0.01) and physical activity energy expenditures (425 +/- 317 versus 574 +/- 342 kcal/d; p0.05). No differences in energy expenditure were noted between groups after controlling for differences in body composition. Daily energy expenditure was examined in a subgroup (n = 11) of AD patients who lost significant body weight (5.6 +/- 2.3 kg) within the past year. There was a lower daily energy expenditure in cachectic AD patients (1799 +/- 474 kcal/d) versus non-cachectic patients (1960 +/- 544 kcal/d) and healthy elderly (2213 +/- 513 kcal/d; p0.01). Similarly, no differences in energy expenditure were noted between groups after controlling for differences in body composition. We conclude that absolute levels of daily energy expenditure are lower in AD patients due to their lower body mass. However, after taking into account differences in body composition, daily energy expenditure in AD patients is appropriate for their metabolic size. The hypothesis that elevated daily energy expenditure contributes to weight loss in AD is not supported by these findings.

Aging is characterized by deleterious changes in body composition and in fat distribution. The mechanisms that determine the aging-associated changes in body composition are not well defined, but the evidence suggests that the loss of fat-free mass is at least partially attributable to physical inactivity. The increase in fat mass may be the result of alterations in fatty acid metabolism. Indeed, fat oxidation is decreased in elderly individuals in several physiological conditions: a) at rest, b) during exercise, and c) in response to meal ingestion (after weight loss). These defects are related in part to loss of fat-free mass, but may also be the consequence of estrogen loss (in women) and/or a decrease in the intrinsic capacity of muscle for fat oxidation, and are amenable to partial correction by exercise training. Special emphasis should be placed in future studies upon the role of steroid hormone in the regulation of fatty acid metabolism in elderly individuals (especially women), as well as therapeutic interventions that may increase the quantity of the fat-free mass and/or fat oxidation.

The independent and collective influences of several physiological factors on the age-related increase in blood pressure in healthy men were examined. Twenty-seven younger and 25 older, mostly normotensive, healthy men were studied. Blood pressure, body fat, body fat distribution, maximal oxygen consumption (VO2max), plasma norepinephrine, dietary Na, and erythrocyte Na-K pump activity were measured. Older men showed 57% higher percent body fat, 40% higher plasma norepinephrine concentration, 14% greater mean arterial blood pressure (MAP), and 5% higher plasma K concentration than younger men (all p < 0.01). Older men showed a 38% (p < 0.01) lower VO2max, 19% (p < 0.05) lower energy intake, 18% (p < 0.05) lower Na-K pump rate constant, and a 17% (p < 0.05) lower Na-K pump rate. Group means for MAP were adjusted for combinations of plasma norepinephrine, waist:thigh ratio, VO2max, and the Na-K pump rate constant, to determine if any one variable or combination could account for the age related increase in MAP. Statistical adjustment for plasma norepinephrine, waist:thigh ratio, and Na-K pump rate constant eliminated the significant difference between MAPs for the two groups. Thus, alterations in sympathetic nervous system activity, body fat distribution, and the membrane Na-K pump activity independently contribute to the age-related increase in MAP in healthy men.

We investigated differences in resting metabolic rate (RMR) and cardiovascular disease risk factors among 86 middle-aged men (36 to 59 years) classified as resistance-trained ([RT] n = 19), aerobic-trained ([AT] n = 37), or untrained ([UT], n = 30) according to habitual exercise patterns. RMR, body composition, body fat distribution, supine blood pressure, maximal aerobic capacity (VO2max), plasma lipid levels, and fasting levels of insulin, glucose, and thyroid hormones were measured. We found that RMR, adjusted for differences in fat-free mass, showed a tendency to be greater in AT men as compared with RT men (P = .09) and was greater in AT men as compared with UT men (P < .05). No differences in RMR were noted between RT and UT men. UT men had higher values for total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), and the insulin to glucose ratio and lower values for high-density lipoprotein cholesterol (HDL-C) (all P < .01) as compared with RT and AT men, whereas no differences in these variables were noted between RT and AT men. Supine diastolic blood pressure was lower in RT men as compared with both AT and UT men. Stepwise regression analysis showed that variations in body fatness accounted for the greatest variation in fasting lipid profile, blood pressure, and the insulin to glucose ratio among groups.(ABSTRACT TRUNCATED AT 250 WORDS)

It was hypothesized that an increase in total and central body fatness is related to higher sympathetic nervous system activity (SNSA) in older men. Resting SNSA was measured from norepinephrine (NE) kinetics in 69 younger (18–36 yr) and 69 healthy older men (55–80 yr). Body fat distribution was estimated from the waist circumference, body composition from underwater weighing, peak oxygen consumption from a treadmill test to exhaustion, and dietary intake from food diaries. Plasma NE concentrations were 41% higher (P < 0.001) in older men due to a 27% increase (P < 0.001) in NE appearance rate and a tendency for a lower NE clearance rate (P = 0.08). NE appearance rate was higher in individuals of both age groups who exhibited a greater waist circumference and body fatness (range of r values 0.49–0.69; P < 0.01). The waist circumference, and not age, was the strongest predictor of the increase in NE appearance rate in older men. Statistically controlling for the waist circumference or body fatness diminished age-related differences in NE concentrations and in NE appearance rate. These findings suggest that an accumulation of total and central body fat is associated with higher levels of SNSA in older males.

The influence of body composition, resting metabolic rate (RMR), and sex on variation in total energy expenditure (TEE) was examined by using meta-analysis (13 published studies in a total of 162 adults). TEE (10.9 +/- 3.2 MJ/d) was significantly correlated with body mass (BM; weighted mean converted r = 0.68, P < 0.05) and resting metabolic rate (RMR; weighted mean converted r = 0.66, P < 0.05). The correlation coefficients, regression coefficients, and intercepts for the regression between TEE and RMR and between TEE and BM were highly variable between studies. When TEE was adjusted for RMR, there was no significant correlation with body fat, and females had a significantly lower TEE than males by 1.1 MJ/d (P = 0.005). We conclude that 1) the relationships between TEE and RMR and TEE and BM are highly variable between studies with nonzero intercepts, precluding use of the traditionally used ratios of TEE to RMR or TEE to BM for data comparison; 2) after adjustment of TEE for RMR, TEE is not associated with adiposity, and women have a significantly lower TEE than men; and, 3) there are insufficient published data to develop prediction models for TEE in adults.

BACKGROUND The age-related increase in blood pressure frequently observed in men and women may be more related to deleterious alterations in physical fitness, body composition, and diet than to a true aging phenomenon. Our purposes were to: (a) characterize the relationship between age and blood pressure in normotensive men and women; (b) identify physiological predictors of the age-related increase in blood pressure; and (c) examine whether the relationship between age and blood pressure persists after controlling for differences in these predictor variables. METHODS Three hundred and sixty four Caucasian men (17-80 yr) and 215 Caucasian women (18-81 yr) were characterized for supine resting blood pressure, peak oxygen consumption, body composition, body fat distribution, plasma insulin and glucose concentrations, and nutritional intake. RESULTS In men, the relationship between age and mean arterial pressure (MAP) (r = .25, p < .01) was no longer significant (partial r = .07, p = .20; 0.03 mmHg increase per year) after four predictor variables of MAP (fat mass, sum of 9 skinfolds, alcohol intake, and supine heart rate) were statistically controlled. In women, the relationship between age and MAP (r = .44, p < .01) no longer existed in women younger than 62 years of age (partial r = .06, p = .46; .04 mmHg increase per year) after three predictor variables of MAP (waist-to-thigh ratio, supine heart rate, and alcohol intake) were held constant, whereas in women older than 62 the relationship persisted (partial r = .37, p < .01; 0.9 mmHg increase per year). CONCLUSION In healthy Caucasian men and women between 17-81 years of age: (a) The relationship between MAP and age was stronger in women than in men, primarily due to an accelerated increase in MAP in women older than 62 years of age; (b) the age-related increase in MAP in men was primarily related to an increase in body fatness, whereas in women the distribution of fat was the primary factor; and (c) after the influence of the predictor variables of MAP were controlled, the relationship between MAP and age persisted in women beyond 62 years of age, but not in women younger than age 62 or in men of any age.

Objective: To determine Trp64Arg β3-adrenoceptor genotype-specific differences in the components of energy expenditure. Hypothesis: We hypothesized that resting metabolic rate (RMR) and physical activity levels would be lower and that thermic effect of feeding (TEF) would be higher in those with the Arg64 allele. Research Methods and Procedures: RMR and TEF were measured by indirect calorimetry, physical activity by questionnaire, and total energy expenditure by the doubly labeled water method. Genotype-specific measures were compared using ANOVA and analysis of covariance (ANCOVA). Results: RMR in Arg64 homozygotes was significantly lower than in Trp64 homozygotes [Arg64, 1373 ± 259 kcal/d (n = 15) vs. Trp64Arg, 1538 ± 238 kcal/d (n = 25) vs. Trp64, 1607 ± 290 kcal/d (n = 22); p < 0.01]. TEF was significantly higher in Arg64 homozygotes compared with Trp64 homozygotes (Arg64, 359 ± 28 kcal/d; Trp64Arg, 322 ± 22 kcal/d; and Trp64, 279 ± 23 kcal/d; p < 0.05). No differences were identified between genotypes in physical activity or in total energy expenditure. Discussion: Our results suggest that the Arg64 β3-adrenoceptor allele contributes significantly to the genetic variability in both RMR and TEF.

Previous cross-sectional studies have suggested that lower levels of insulin-like growth factor-1 (IGF-1) in older persons are related in part to diminished physical exercise. However, it is unknown whether the introduction of long-term exercise in previously inactive older individuals increases IGF-1, and whether the response is different between older men and women. Thus, we examined the effects of 8 weeks of endurance training on changes in IGF-1, IGF-1 binding protein-1 (IGFBP-1), IGFBP-3, and maximal aerobic power (VO2max) in 18 older individuals (aged 66.1 +/- 1.4 years, 10 men and eight women). Individuals were also characterized for changes in body composition, estimated energy intake, and fasting plasma levels of glucose, insulin, and glucagon before and after an exercise training program. Endurance training increased VO2max similarly in men (14%, P < .01) and women (14%, P < .01), but women showed a smaller increase in IGF-1 (8%, NS) than men (19%, P < .01). The correlation between changes in VO2max and IGF-1 was significant in men (r = .79, P < .02), but not in women (r = .22, NS). Although no mean group change in IGFBP-1 or IGFBP-3 was noted, the individual changes between IGF-1 and IGFBP-3 showed a tendency to be related in men (r = .48, P = .15), but not in women (-.21, NS). Exercise training decreased plasma glucose (P < .05) in men, but not in women.(ABSTRACT TRUNCATED AT 250 WORDS)

Two studies on resting metabolic rate (RMR) in bulimia nervosa were conducted. The first study compared RMR before treatment in 25 normal-weight women with bulimia nervosa and 20 control subjects of similar height, weight, body composition, age, and activity level. No significant difference in RMR adjusted for fat-free weight was observed. The second study sought to determine whether RMR in women with bulimia nervosa changed if they ceased vomiting and resumed eating in a more normal fashion after cognitive-behavioral treatment. There was no differential change in RMR from pre- to posttreatment for the "improved" bulimics (9 of 12 subjects who received treatment) relative to 13 control subjects who were also tested twice at the same time intervals as the treated bulimia nervosa subjects. These findings do not support the hypothesis that normal-weight women with bulimia nervosa have a suppressed RMR, nor is it altered with treatment compared with matched control subjects.