Obesity: Poehlman ET

Karelis AD, St-Pierre DH, Conus F, Rabasa-Lhoret R, Poehlman ET. · Département de Nutrition, Unité Métabolique, Université de Montréal, Montréal, Québec, Canada H3T 1A8. · J Clin Endocrinol Metab. · Pubmed #15181025 links to  free full text

Abstract: 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.

St-Pierre DH, George V, Rabasa-Lhoret R, Poehlman ET. · Unité Métabolique, Département de Nutrition, Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada. · Nutrition. · Pubmed #14698030 No free full text.

This publication has no abstract.

Brochu M, Poehlman ET, Ades PA. · Division of Cardiology, University of Vermont College of Medicine, Burlington, USA. · J Cardiopulm Rehabil. · Pubmed #10763157 No free full text.

Abstract: 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.

Gannon B, DiPietro L, Poehlman ET. · Division of Clinical Pharmacology and Metabolic Research, Department of Medicine, University of Vermont, Burlington 05405, USA. · Int J Obes Relat Metab Disord. · Pubmed #10702744 No free full text.

Abstract: OBJECTIVE: To review current studies that examine differences in energy expenditure between African Americans and Caucasians as possible modulators of attained differences in overweight status. DESIGN: Literature review of recent clinical and laboratory studies. METHODS: Studies chosen for review were those that examined directly resting metabolic rate (RMR), using indirect calorimetry, and total daily energy expenditure (TDEE) and physical activity energy expenditure (PAEE), using doubly labeled water. RESULTS: Ten of 15 studies reviewed reported a lower RMR in African Americans than in Caucasians. The differences in RMR between African Americans and Caucasians ranged from 81 to 274 kcal/day and could not be explained by differences in age, fat-free mass (FFM) or methodological concerns. Two of six studies of energy expenditure using doubly labeled water suggest that Black adults have a tendency for lower TDEE that can be accounted for primarily by a lower PAEE. CONCLUSIONS: If future studies indicate conclusively that African Americans do have lower RMR, TDEE and PAEE than Caucasians, then the disproportionally higher risk of obesity and associated metabolic disorders in Black adults may be preventable-especially in Black women. If these race differences are indeed a result of both physiological and behavioral factors, then interventions designed to reduce caloric intake and/or increase energy expenditure through lifestyle activity or structured exercise programs become especially important for African Americans and should be encouraged. International Journal of Obesity (2000)24, 4-13

Brochu M, Tchernof A, Turner AN, Ades PA, Poehlman ET. · Departments of Kinesiology and Nutrition, University of Montréal, Québec, Canada. · Metabolism. · Pubmed #12759890 No free full text.

Abstract: It is presently unclear how much visceral adipose tissue (VAT) loss is needed to induce favorable metabolic changes. Cross-sectional studies have proposed that a threshold level of VAT exceeding 110 cm(2) in women induces deleterious changes in the metabolic profile. It is presently unclear, however, if significant decreases in VAT below this given threshold significantly improve the metabolic profile more as compared to decreases that remain below 110 cm(2). To examine whether achieving versus not achieving the proposed VAT threshold impacts differently on the metabolic profile in postmenopausal women, we examined the effects of a VAT loss below the 110-cm(2) threshold versus those individuals who remained higher than 110 cm(2) after a weight loss program. Twenty-five sedentary obese (baseline % body fat, 47.7% +/- 4.1%; [mean +/- SD]) postmenopausal women aged between 51 and 71 years (59.7 +/- 5.6 years) and displaying high baseline levels of VAT accumulation (223 +/- 45 cm(2)) were submitted to a 1-year weight loss program with weight stabilization periods before and after weight reduction. Based on their loss of VAT after weight loss, subjects were characterized as "attainers" (post VAT levels < 110 cm(2); average, 96 +/- 10 cm(2); n = 10) or "non-attainers" (post VAT levels > 110 cm(2); average, 171 +/- 34 cm(2); n = 15). We compared changes in (1) plasma lipid-lipoprotein levels, (2) insulin sensitivity (euglycemic/hyperinsulinemic clamp), and (3) supine resting blood pressure between groups who achieved these 2 distinct levels of VAT. Attainers showed a 2-fold greater loss of VAT compared to non-attainers (-51.5% v -27.5%, P <.001). Attainers also showed a greater loss of body weight (-19.0% v -12.5%, P <.01) and fat mass (-34.8% v -18.4%, P <.001) after the program compared to non-attainers. Despite significant differences in the loss of total fat and VAT after the weight loss program, attainers and non-attainers showed comparable improvements for plasma high-density lipoprotein-cholesterol (HDL-chol) levels (+62.5% v +50.0%, P = not significant [NS]), cholesterol/HDL-chol ratio (-45.5% v -36.5%, P = NS), insulin sensitivity (+34.1% v +23.2%, P = NS), and resting systolic (-6.9% v -5.1%, P = NS) and diastolic (-11.3% v -11.1%, P = NS) blood pressure. These results do not favor the idea that attaining levels of VAT below a threshold of 110 cm(2) is necessary to favorably improve the metabolic profile in obese postmenopausal women. Achieving or not the proposed threshold of VAT, independently of baseline values, appears to yield similar metabolic improvements in obese postmenopausal women. More moderate losses of VAT appear to yield similar metabolic improvements as large losses.

Rawson ES, Nolan A, Silver K, Shuldiner AR, Poehlman ET. · Department of Medicine, University of Vermont, Burlington, VT, USA. · Metabolism. · Pubmed #12037740 No free full text.

Abstract: 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 <.0001) when analyzed with the 2 genotypes combined, but no significant differences between carriers and noncarriers with respect to change in these variables (group x time interaction term, all P >.05). Total energy expenditure tended to be reduced (490 kJ x d(-1), P =.13) in both groups following weight loss, but there was no significant group x time interaction term (P =.78), indicating no difference in the response of the 2 genotypes. There was a 9% reduction in RMR (611 kJ x d(-1), P <.001) when both groups were considered together, but no significant group x 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 >.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.

Tchernof A, Nolan A, Sites CK, Ades PA, Poehlman ET. · Department of Medicine, College of Medicine, University of Vermont, Burlington. · Circulation. · Pubmed #11827920 links to  free full text

Abstract: BACKGROUND: C-reactive protein (CRP) has been proposed as an independent risk factor for cardiovascular disease and has been positively associated with body weight and body fatness. We examined the hypothesis that weight loss would reduce plasma CRP levels in obese postmenopausal women. METHODS AND RESULTS: In a sample of 61 obese (body mass index, 35.6 +/- 5.0 kg/m(2)), postmenopausal women (age, 56.4 +/- 5.2 years), we found that plasma CRP levels were positively associated with dual x-ray absorptiometry-measured total body fatness (r=0.36, P<0.005) and CT-measured intra-abdominal body fat area (r=0.30, P<0.02). Significant correlations were also found between plasma CRP and triglyceride levels (r=0.33, P<0.009) and glucose disposal measured by the hyperinsulinemic-euglycemic clamp technique (r=-0.29, P<0.03). Twenty-five of the 61 women tested at baseline completed a weight loss protocol. The average weight loss was 14.5 +/- 6.2 kg (-15.6%, P<0.0001), with losses of 10.4 +/- 5.4 kg fat mass (-25.0%, P<0.0001) and 2.8 +/- 1.4 kg fat-free mass (-6.0%, P<0.0001). Visceral and subcutaneous fat areas were reduced by -36.4% and -23.7%, respectively (P<0.0001). Plasma CRP levels were significantly reduced by weight loss: average -32.3%, from 3.06 (+0.69, -1.29) to 1.63 (+0.70, -0.75) microgram/mL (P<0.0001, medians and interquartile differences). Changes in body weight and in total body fat mass were both positively associated with plasma CRP level reductions. CONCLUSIONS: Adiposity was a significant predictor of plasma CRP in postmenopausal women on a cross-sectional basis. Moreover, caloric restriction-induced weight loss decreased plasma CRP levels. Weight loss may represent an important intervention to reduce CRP levels, which may mediate part of its cardioprotective effects in obese postmenopausal women.

Sites CK, Brochu M, Tchernof A, Poehlman ET. · Departments of Obstetrics and Gynecology and Medicine, The University of Vermont College of Medicine, Burlington, VT 05405, USA. · Metabolism. · Pubmed #11436191 No free full text.

Abstract: The aim of this study was to compare the effect of hormone replacement therapy (HRT) on insulin resistance and central adiposity in obese postmenopausal women. Forty-five obese postmenopausal women (16 HRT users and 29 nonusers), with a mean age of 56.6 +/- 5.3 years and duration of current, continuous HRT use of 4.7 +/- 2.9 years, were included in the study. Subjects were studied using oral glucose tolerance tests, euglycemic clamping, dual photon x-ray absorptiometry, computed tomography, doubly labeled water, and treadmill testing. Insulin sensitivity, total fat, visceral fat, subcutaneous abdominal fat, thigh muscle attenuation, daily physical activity energy expenditure, peak oxygen consumption (Vo(2)) were measured. HRT users had lower body weight (88.0 +/- 11.0 v 98.2 +/- 15.0 kg, P =.05), lower body mass index (33.1 +/- 3.5 v 36.8 +/- 5.2 kg/m(2), P =.05), lower fat mass (38.3 +/- 7.3 v 44.1 +/- 10 kg, P =.05), less visceral adipose tissue (157 +/- 47 v 211 +/- 81 cm(2); P =.05), and higher peak Vo(2) (21.1 +/- 4.6 v 17.6 +/- 2.2 mL/kg/min, P =.001) than nonusers. After adjustment for total fat, we noted a trend for decreased visceral adipose tissue in HRT users (P =.09). After adjustment for peak Vo(2), the decreased visceral adipose tissue persisted in HRT users (P <.01). Insulin sensitivity per kilogram of lean body mass did not differ between HRT users (0.51 +/- 0.22 mmol/kg/min) and nonusers (0.49 +/- 0.22 mmol/kg/min). It was concluded that obese postmenopausal women using HRT have a more favorable body composition and fat distribution pattern than nonusers. Although visceral adipose tissue is decreased in HRT users, insulin sensitivity does not differ between HRT users and nonusers.

Brochu M, Starling RD, Tchernof A, Matthews DE, Garcia-Rubi E, Poehlman ET. · Department of Medicine, University of Vermont College of Medicine, Burlington 05405, USA. · J Clin Endocrinol Metab. · Pubmed #10902782 links to  free full text

Abstract: 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 x 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.

Brochu M, Poehlman ET, Savage P, Ross S, Ades PA. · Division of Cardiology, University of Vermont College of Medicine, Burlington, USA. · Coron Artery Dis. · Pubmed #10758815 No free full text.

Abstract: BACKGROUND: 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. METHODS: 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. RESULTS: 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, P < 0.05) and cholesterol/high-density lipoprotein cholesterol (HDL-C) ratio (r2 = 0.13, P < 0.01). Body weight, rather than body fat distribution, was the best predictor of plasma HDL-C concentration (r2 = 0.14, P < 0.01) and fasting glucose concentrations (r2 = 0.10, P < 0.05). Fat mass was the best anthropometric predictor of fasting plasma insulin concentrations (r2 = 0.38, P < 0.0001) and for the glucose-insulin ratio (r2 = 0.39, P < 0.0001) 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. CONCLUSION: 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.

Tchernof A, Toth MJ, Poehlman ET. · Department of Medicine, University of Vermont, Burlington 05405, USA. · Diabetes Care. · Pubmed #10546023 links to  free full text

Abstract: OBJECTIVE: Low sex hormone-binding globulin (SHBG) levels in women are associated not only with hyperinsulinemia, increased risk for cardiovascular disease, and type 2 diabetes but also with excess body fatness and abdominal obesity. We tested the hypothesis that an elevated total or intra-abdominal adipose tissue accumulation mediates the relationship between low SHBG levels and an altered metabolic profile. RESEARCH DESIGN AND METHODS: We measured body composition (dual-energy X-ray absorptiometry [DEXA]) and body fat distribution (computed tomography) in 52 middle-aged (46.7 +/- 0.4, mean +/- SEM) premenopausal women. Insulin and glucose responses to a 75-g oral glucose load and plasma lipid-lipoprotein levels were also measured. RESULTS: Low plasma SHBG concentrations were associated with increased total body fat mass (r = -0.41, P < 0.005) and subcutaneous abdominal (r = -0.39, P < 0.005) and intra-abdominal (r = -0.37, P < 0.008) adipose tissue area. Low SHBG was also associated with a greater insulin response to oral glucose (r = -0.40, P < 0.005), higher triglyceride levels (r = -0.29, P < 0.05), higher cholesterol/HDL cholesterol ratio (r = -0.51, P < 0.005), but lower HDL cholesterol concentrations (r = 0.65, P < 0.005). When matched for intra-abdominal fat or total fat mass, subjects with either low or high SHBG showed no difference in the insulin response to an oral glucose challenge. Statistical adjustment for differences in intra-abdominal adipose tissue accumulation or total body fat mass also eliminated the associations between SHBG levels and metabolic variables, with the exception of the association between SHBG and HDL cholesterol levels (r = 0.52, P < 0.005). CONCLUSIONS: Our results suggest that the previously reported relationship between low SHBG levels and increased metabolic disease risk in women is mediated, to a large extent, by concomitant variation in body fatness and intra-abdominal adipose tissue accumulation.

Tchernof A, Starling RD, Walston JD, Shuldiner AR, Dvorak RV, Silver K, Matthews DE, Poehlman ET. · Department of Medicine, College of Medicine, University of Vermont, Burlington 05405, USA. · Diabetes. · Pubmed #10389848 links to  free full text

Abstract: 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.

Conus F, Allison DB, Rabasa-Lhoret R, St-Onge M, St-Pierre DH, Tremblay-Lebeau A, Poehlman ET. · Unité Metabolique, Département de Nutrition, Faculté de Médecine, Université de Montréal, Montréal, Québec H3T 1A8, Canada. · J Clin Endocrinol Metab. · Pubmed #15472199 links to  free full text

Abstract: 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.

Savage PD, Brochu M, Poehlman ET, Ades PA. · Division of Cardiology, University of Vermont College of Medicine, Burlington, Vt, USA. · Am Heart J. · Pubmed #12891202 No free full text.

Abstract: BACKGROUND: The majority of patients with coronary heart disease (CHD) are overweight. However, little weight loss occurs with participation in a standard cardiac rehabilitation (CR) program. METHODS: Fifteen overweight patients (average body mass index of 31.0 kg/m2) with CHD completed a 4-month exercise training program in a CR program. The exercise program consisted primarily of walking long duration (60-90 minutes per session) 5 to 7 days per week at a relatively low intensity of 50% to 60% of peak VO2. Measures of body composition by dual-energy x-ray absorptiometry, body fat distribution by computed tomography, plasma lipid-lipoprotein, glucose and insulin concentrations, and peak VO2 were obtained before and after the exercise intervention. Patients maintained an isocaloric diet throughout the study. RESULTS: Patients had reductions in total body weight (-4.6 kg), fat mass (-3.6 kg), percent body fat (-2.9%), and waist circumference (-5.6 cm) (all P <.001) while maintaining fat-free mass. Subcutaneous adipose tissue was reduced by 12% (P <.001) and visceral adipose tissue was lowered by 14% (P <.001). There were favorable changes in the lipid-metabolic profile with reductions in triglyceride levels (-23.7%), total cholesterol/HDL-C ratio (-14.3%), and fasting insulin levels (-22.3%) (all P <.05). Peak VO2 increased by 21.2% (P <.001). CONCLUSIONS: The present pilot study results suggest that a high caloric training exercise training program in the CR setting may be effective in promoting weight loss and improving coronary risk factors in overweight coronary patients. Although additional research with randomized control patients is needed, this alternative to traditional CR may be considered to maximize weight loss as part of a secondary prevention program.

Walston J, Andersen RE, Seibert M, Hilfiker H, Beamer B, Blumenthal J, Poehlman ET. · Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · Obes Res. · Pubmed #12690078 No free full text.

Abstract: OBJECTIVE: To determine Trp64Arg beta(3)-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 beta(3)-adrenoceptor allele contributes significantly to the genetic variability in both RMR and TEF.

Dionne IJ, Garant MJ, Nolan AA, Pollin TI, Lewis DG, Shuldiner AR, Poehlman ET. · Clinical Pharmacology and Metabolic Research Unit, Department of Medicine, University of Vermont, Burlington, Vermont, USA. · Int J Obes Relat Metab Disord. · Pubmed #12032746 links to  free full text

Abstract: INTRODUCTION: Genetic variants affecting adrenoceptors have been suggested to influence body fatness. A putative gain-of-function polymorphism in the beta(1)-adrenoceptor was recently discovered (Gly389Arg ADRB1). We examined the association between Gly389Arg ADRB1 and obesity status in a large cohort of well-characterized individuals. METHODS: First, a large cohort of 931 Caucasian women (55.0+/-12.2 y) were genotyped for Gly389Arg ADRBbeta1 and we examined the association of the Arg allele with body weight and BMI (Gly/Gly, n=54; Gly/Arg, n=360; Arg/Arg, n=517). To further examine phenotypes regulating energy balance and body fatness, we examined the contribution of the Arg allele to body composition (DEXA), fat distribution (CT scan), resting energy expenditure, energy and macronutrient intake, maximal oxygen capacity, and physical activity in a subsample of 214 women from the main cohort that had been carefully characterized (Gly/Gly, n=19; Gly/Arg, n=82; Arg/Arg, n=113). RESULTS: In the entire cohort (n=931), allele frequencies were 0.25 and 0.75 for the Gly and Arg alleles, respectively. In this cohort, we found that each Arg allele was associated with greater body weight of 2.91 kg (P=0.01) and BMI of 0.86 kg/m(2) (P=0.05). Accordingly, in the subsample of women, each Arg allele was associated with greater fat mass (3.71 kg; P=0.008). Other phenotypes were not significantly associated with the presence of the Arg allele. CONCLUSIONS: This is the first study to investigate the relationship between the Gly389Arg ADRB1 variant and obesity. We found that the Arg allele is associated with greater body weight and BMI in Caucasian women due to a greater fat mass.

Kimm SY, Glynn NW, Aston CE, Damcott CM, Poehlman ET, Daniels SR, Ferrell RE. · Department of Family Medicine and Clinical Epidemiology, School of Medicine, University of Pittsburgh, PA 15261, USA. · Am J Clin Nutr. · Pubmed #11916758 links to  free full text

Abstract: BACKGROUND: Lower resting energy expenditure (REE) in African American women may contribute to their obesity. The identification of uncoupling protein (UCP) genes has fueled a search for genes involved in energy metabolism in humans. OBJECTIVE: We examined variation in REE in relation to variation in UCP1, UCP2, and UCP3 in 141 women aged 18-21 y. DESIGN: Standard methods were used for REE measurements and genetic analysis. Body composition was determined with the use of dual-energy X-ray absorptiometry. Multivariate analysis was used to examine the effect of genotypes on REE and on fat mass in relation to other potentially confounding variables. RESULTS: REE was 295 kJ/d lower in African American women than in white women. No significant variation in REE was seen for UCP1, UCP2, and UCP3 (p-55; exon 3a; and exon 3b) variants after adjustment for other variables including smoking status. For the UCP3 exon 5 variant, REE was significantly (P = 0.019) lower in African American women with the CC genotype than in those with the TT genotype. In African American women, there was a significant trend (P = 0.012) toward lower REE and a weak but nonsignificant trend (P = 0.1) toward greater fat mass across the 3 genotypes (TT, CT, and CC). CONCLUSIONS: The significant and dose-dependent relation between lower REE and the C allele suggests that it may be a thrifty allele. The presence of this parsimonious energy metabolism in African American women, possibly linked to UCP3, may be implicated in their susceptibility to obesity. The absence of a UCP3 effect in white women is intriguing and needs to be explored to further understand possible interactions between UCP3 and other genes.

Mentuccia D, Proietti-Pannunzi L, Tanner K, Bacci V, Pollin TI, Poehlman ET, Shuldiner AR, Celi FS. · Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland, Baltimore, Maryland 21201, USA. · Diabetes. · Pubmed #11872697 links to  free full text

Abstract: 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 beta-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 beta-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 plus minus 0.02 mg center dot min(-1) center dot kg(-1) fat-free mass Ala92 homozygotes vs. 0.44 plus minus 0.02 Ala92 heterozygotes vs. 0.42 plus minus 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 plus minus 0.9 kg/m(2) vs. neither variant 33.1 plus minus 0.4 kg/m(2), 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.

Harvey-Berino J, Gold EC, West DS, Shuldiner AR, Walston J, Starling RD, Nolan A, Silver K, Poehlman ET. · Department of Nutrition and Food Sciences, University of Vermont, Burlington 05405-0148, USA. · J Am Diet Assoc. · Pubmed #11716317 No free full text.

This publication has no abstract.

Kimm SY, Glynn NW, Aston CE, Poehlman ET, Daniels SR. · Department of Family Medicine and Clinical Epidemiology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA. kimm+@pitt.edu · Am J Epidemiol. · Pubmed #11590084 links to  free full text

Abstract: The prevalence of obesity is higher in Black women than in White women (JAMA 1994;272:205-11; Arch Pediatr Adolesc Med 1995;149:1085-91). Although it has been shown that Black women have a lower resting energy expenditure (REE), factors affecting REE remain unclear. This 1996-1997 study in Cincinnati, Ohio, assessed racial differences in REE and their determinants in a biracial cohort of 152 healthy young women aged 18-21 years. Two indirect calorimetric measurements were obtained during two overnight hospital admissions 10-14 days apart. Body composition was measured by using dual-energy x-ray absorptiometry. Mean REE (adjusted for body composition, smoking, and contraceptive medication use) was significantly (p = 0.04) lower by 71 kcal/day in Black women (1,453 (standard error, 21) kcal/day) than in White women (1,524 (standard error, 19) kcal/day). Smoking was associated with a REE that was 68 kcal/day higher for both groups (p = 0.03). A trend (p = 0.07) toward increased REE (by 46 kcal/day) was found with contraceptive medication use. In conclusion, young Black women had a significantly lower REE than did White women. Cigarette smoking significantly increased REE. The apparent presence of a more parsimonious energy metabolism in Black women suggests that maintenance of energy homeostasis requires particular vigilance in this high-risk population.

Sites CK, L'Hommedieu GD, Brochu M, Poehlman ET. · Departments of Obstetrics and Gynecology and Medicine, The University of Vermont College of Medicine, Burlington, Vermont 05405, USA. · Menopause. · Pubmed #11449086 No free full text.

Abstract: OBJECTIVE: The quantity of intra-abdominal fat is highly associated with the development of diabetes mellitus. We sought to determine whether recent hormone replacement therapy (HRT) use modifies central fat and insulin sensitivity in postmenopausal women compared with women who had never used HRT. DESIGN: We measured intra-abdominal fat, subcutaneous abdominal fat, and sagittal diameter at the L4-L5 vertebral disc space using computed tomography imaging. Total body fat and fat-free mass were measured using dual energy x-ray absorptiometry. Insulin sensitivity was assessed using the euglycemic hyperinsulinemic clamp technique in 42 nonobese postmenopausal women, age 51 +/- 4 years (12 recent HRT users plus 30 never-users). All women who were taking HRT discontinued it for 2 months before the study. RESULTS: After statistical adjustment for age, previous use of HRT was associated with decreased intra-abdominal fat (72 +/- 34 cm2) compared with no HRT use (96 +/- 33 cm2; p = 0.05). This difference remained significant after adjustment for time since menopause. When previous HRT users were compared with nonusers, there were no differences in subcutaneous abdominal fat, sagittal diameter, fat-free mass, total fat, insulin sensitivity, or body weight. CONCLUSIONS: Recent HRT use is associated with lower intra-abdominal fat in nonobese, early postmenopausal women. This finding suggests a carry-over effect of HRT on intra-abdominal fat. Recent HRT use does not seem to be associated with differences in glucose disposal.

Brochu M, Tchernof A, Dionne IJ, Sites CK, Eltabbakh GH, Sims EA, Poehlman ET. · Department of Medicine, Division of Clinical Pharmacology and Metabolic Research, University of Vermont College of Medicine, Burlington, Vermont 05405, USA. · J Clin Endocrinol Metab. · Pubmed #11238480 links to  free full text

Abstract: 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 cm(2); P: < 0.01). No difference was noted between groups for abdominal sc adipose tissue (453 +/- 126 vs. 442 +/- 144 cm(2); 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 (<20 yr old) compared with 29% of the MAO subjects (P: = 0.09). Stepwise regression analysis showed that visceral adipose tissue and the age-related onset of obesity explained 22% and 13%, respectively, of the variance observed in insulin sensitivity (total r(2) = 0.35; P: < 0.05 in both cases). 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.

Dionne IJ, Turner AN, Tchernof A, Pollin TI, Avrithi D, Gray D, Shuldiner AR, Poehlman ET. · Department of Medicine, College of Medicine, University of Vermont, Burlington 05405, USA. · Diabetes. · Pubmed #11147800 links to  free full text

Abstract: Several adrenoceptor subtypes are expressed in adipocytes, which together exert their influence on adipocyte metabolism. Therefore, we specifically examined the interactive effect of Trp64Arg (beta3) and Glu12/Glu9 (alpha2b) adrenoceptor (AR) polymorphisms on energy metabolism and body composition in healthy women with a wide range of body habitus. We genotyped 909 unrelated women (age 55 +/- 12 [mean +/- SD] years, range 19-87; body weight 88 +/- 22 kg, range 40-167; and BMI 33 +/- 8 kg/m2, range 16-64) for Trp64Arg beta3AR and Glu12/Glu9 alpha2bAR variants. We examined the independent effect of the Glu12/Glu9 alpha2bAR variant on body composition and energy balance, in a large cohort of Caucasian women (n = 909). A second goal was to examine the interaction effect of Glu12/Glu9 alpha2bAR and Trp64Arg beta3AR on the same phenotypes. The obesity-related phenotypes studied were as follows: body weight, BMI, fat mass, visceral fat, fat-free mass, resting metabolic rate (RMR), VO2max, leisure time physical activity, and daily energy intake. Body composition and body fat distribution were measured by dual-energy X-ray absorptiometry and radiographic imagery, VO2max by a treadmill test to exhaustion, and RMR by indirect calorimetry. An analysis of covariance indicated that in the entire cohort, there was no significant difference between Glu12/Glu9 alpha2bAR carriers and control subjects for any of the obesity-related phenotypes that were examined. However, we observed a significant interaction effect of the Trp64Arg and Glu12/Glu9 variants on fat mass (P = 0.009) and percent fat (P = 0.016). Age, height, body weight, BMI, fat-free mass, visceral fat, energy expenditure, respiratory quotient, physical fitness, and energy intake were not different among groups. Collectively, these findings support an interaction effect of the two adrenoceptor variants on body fatness in Caucasian women, although the physiological mechanism by which they exert this effect remains to be determined.

Tchernof A, Starling RD, Turner A, Shuldiner AR, Walston JD, Silver K, Poehlman ET. · Department of Medicine, College of Medicine, University of Vermont, Burlington 05405, USA. · Diabetes. · Pubmed #11016455 links to  free full text

Abstract: 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.

Toth MJ, Tchernof A, Sites CK, Poehlman ET. · Division of Clinical Pharmacology and Metabolic Research, Department of Medicine and Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Vermont, Burlington, VT 05405, USA. · Int J Obes Relat Metab Disord. · Pubmed #10702775 No free full text.

Abstract: OBJECTIVE: 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. DESIGN: Cross-sectional. SUBJECTS: Fifty-three healthy, middle-aged, premenopausal women (mean+/-SD; 47+/-3 y) and 28 early-postmenopausal women (51+/-4 y). MEASUREMENTS: Total and regional body composition by dual energy X-ray absorptiometry and abdominal fat distribution by computed tomography. RESULTS: 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 P<0.01) in postmenopausal women compared with premenopausal women. Postmenopausal women had a 49% greater intra-abdominal (88+/-32 vs 59+/-32 cm2; P<0.01) and a 22% greater abdominal subcutaneous fat area (277+/-93 vs 227+/-108 cm2; P<0.05) compared to premenopausal women. The menopause-related difference in intra-abdominal fat persisted (P<0.05) 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. CONCLUSION: 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