Postprandial thermogenesis and substrate oxidation are unaffected by sleep restriction.

BACKGROUND/OBJECTIVES: The extent to which alterations in energy expenditure (EE) in response to sleep restriction contribute to the short sleep-obesity relationship is not clearly defined. Short sleep may induce changes in resting metabolic rate (RMR), thermic effect of food (TEF) and postprandial substrate oxidation. SUBJECTS/METHODS: Ten females (age and body mass index: 22-43 years and 23.4-28 kg m(-2)) completed a randomized, crossover study assessing the effects of short (4 h per night) and habitual (8 h per night) sleep duration on fasting and postprandial RMR and respiratory quotient (RQ). Measurements were taken after three nights using whole-room indirect calorimetry. The TEF was assessed over a 6-h period following consumption of a high-fat liquid meal. RESULTS: Short versus habitual sleep did not affect RMR (1.01±0.05 and 0.97±0.04 kcal min(-1); P=0.23). Fasting RQ was significantly lower after short versus habitual sleep (0.84±0.01 and 0.88±0.01; P=0.028). Postprandial EE (short: 1.13±0.04 and habitual: 1.10±0.04, P=0.09) and RQ (short: 0.88±0.01 and habitual: 0.88±0.01, P=0.50) after the high-fat meal were not different between conditions. TEF was similar between conditions (0.24±0.02 kcal min(-1) in both; P=0.98), as was the ~6-h incremental area under the curve (1.16±0.10 and 1.17±0.09 kcal min(-1) × 356 min after short and habitual sleep, respectively; P=0.92). CONCLUSIONS: Current findings observed in non-obese healthy premenopausal women do not support the hypothesis that alterations in TEF and postprandial substrate oxidation are major contributors to the higher rate of obesity observed in short sleepers. In exploring a role of sleep duration on EE, research should focus on potential alterations in physical activity to explain the increased obesity risk in short sleepers.

MRI-measured pelvic bone marrow adipose tissue is inversely related to DXA-measured bone mineral in younger and older adults.

BACKGROUND/OBJECTIVES: Recent research has shown an inverse relationship between bone marrow adipose tissue (BMAT) and bone mineral density (BMD). There is a lack of evidence at the macro-imaging level to establish whether increased BMAT is a cause or effect of bone loss. This cross-sectional study compared the BMAT and BMD relationship between a younger adult group at or approaching peak bone mass (PBM; age 18.0-39.9 years) and an older group with potential bone loss (PoBL; age 40.0-88.0 years). SUBJECTS/METHODS: Pelvic BMAT was evaluated in 560 healthy men and women with T1-weighted whole-body magnetic resonance imaging. BMD was measured using whole-body dual-energy X-ray absorptiometry. RESULTS: An inverse correlation was observed between pelvic BMAT and pelvic, total and spine BMD in the younger PBM group (r=-0.419 to -0.461, P<0.001) and in the older PoBL group (r=-0.405 to -0.500, P<0.001). After adjusting for age, sex, ethnicity, menopausal status, total body fat, skeletal muscle, subcutaneous and visceral adipose tissue, neither subject group (younger PBM vs older PoBL) nor its interaction with pelvic BMAT significantly contributed to the regression models with BMD as dependent variable and pelvic BMAT as independent variable (P=0.434-0.928). CONCLUSIONS: Our findings indicate that an inverse relationship between pelvic BMAT and BMD is present both in younger subjects who have not yet experienced bone loss and also in older subjects. These results provide support at the macro-imaging level for the hypothesis that low BMD may be a result of preferential differentiation of mesenchymal stem cells from osteoblasts to adipocytes.

Ethnic and sex differences in bone marrow adipose tissue and bone mineral density relationship.

UNLABELLED: The relationship between bone marrow adipose tissue and bone mineral density is different between African Americans and Caucasians as well as between men and women. This suggests that the mechanisms that regulate the differentiation and proliferation of bone marrow stromal cells may differ in these populations. INTRODUCTION: It has long been established that there are ethnic and sex differences in bone mineral density (BMD) and fracture risk. Recent studies suggest that bone marrow adipose tissue (BMAT) may play a role in the pathogenesis of osteoporosis. It is unknown whether ethnic and sex differences exist in the relationship between BMAT and BMD. METHODS: Pelvic BMAT was evaluated in 455 healthy African American and Caucasian men and women (age 18-88 years) using whole-body T1-weighted magnetic resonance imaging. BMD was measured using whole-body dual-energy X-ray absorptiometry. RESULTS: A negative correlation was observed between pelvic BMAT and total body BMD or pelvic BMD (r = -0.533, -0.576, respectively; P < 0.001). In multiple regression analyses with BMD as the dependent variable, ethnicity significantly entered the regression models as either an individual term or an interaction with BMAT. Menopausal status significantly entered the regression model with total body BMD as the dependent variable. African Americans had higher total body BMD than Caucasians for the same amount of BMAT, and the ethnic difference for pelvic BMD was greater in those participants with a higher BMAT. Men and premenopausal women had higher total body BMD levels than postmenopausal women for the same amount of BMAT. CONCLUSIONS: An inverse relationship exists between BMAT and BMD in African American and Caucasian men and women. The observed ethnic and sex differences between BMAT and BMD in the present study suggest the possibility that the mechanisms regulating the differentiation and proliferation of bone marrow stromal cells may differ in these populations.

Fat-free mass index: changes and race/ethnic differences in adulthood.

OBJECTIVE: Nutritional status is assessed by measuring BMI or percent body fat (%fat). BMI can misclassify persons who carry more weight as fat-free mass and %fat can be misleading in cases of malnutrition or in disease states characterized by wasting of lean tissue. The fat-free mass index (FFMI) is proposed to assess body composition in individuals who have a similar body composition but differ in height allowing identification of those suffering from malnutrition, wasting or those that possess a relatively high muscle mass. The purpose was to determine whether the FFMI differs in a group of racially/ethnically diverse adults. DESIGN: Cross-sectional. SUBJECTS: Subjects were a multi-ethnic sample (Caucasian, CA; African American, AA; Hispanic, HIS and Asian, AS) of 1339 healthy males (n = 480) and females (n = 859) ranging in age from 18-110 years. Total body fat, total fat-free mass and bone mineral density were estimated using dual energy X-ray absorptiometry. RESULTS: FFMI differed among the four ethnic groups (P ≤ 0.05) for both genders. A curvilinear relationship was found between age and FFMI for both genders although the coefficients in the quadratic model differed between genders (P ≤ 0.001) indicating the rate of change in FFMI differed between genders. The estimated turning point where FFMI started to decline was in the mid 20s for male and mid 40s for female participants. An age × gender interaction was found such that the rate of decline was greater in male than female participants (P ≤ 0.001). For both genders, FFMI was greatest in AA and the least in AS (P ≤ 0.001). There was no significant interaction between race and age or age(2) (P = 0.06). However, male participants consistently had a greater FFMI than female participants (P ≤ 0.001). CONCLUSIONS: These findings have clinical implications for identifying individuals who may not be recognized as being malnourished based on their BMI or %fat but whose fat-free mass corrected for height is relatively low.

Intermuscular and subcutaneous adipose tissue distributions differ in HIV+ versus HIV-men and women.

BACKGROUND: Loss of subcutaneous (SAT) with sparing of visceral (VAT) adipose tissue (AT) has been documented in HIV + men and women. Intermuscular AT (IMAT) rivals VAT in independent associations with cardiovascular risk. OBJECTIVE: To determine whether the size and distribution of IMAT differs in HIV+ vs. HIV- men and/or women. DESIGN: We used whole-body MRI to measure VAT, IMAT and four SAT compartments and compared them by HIV status using whole-body skeletal muscle (SM) or total AT (TAT) as co-variates in multi-ethnic groups of healthy HIV- (n=86) and stable HIV+ (n=76) men and women. RESULTS: The sizes of AT depots (adjusting for SM) did not differ by HIV status, except for smaller gluteal SAT (lower trunk, between L(4)-L(5) to greater trochanter) in both sexes (P<0.05). The AT distribution (adjusting for TAT) was significantly different, with larger VAT (P<0.05) and smaller gluteal and limb SAT (P<0.05) in both HIV+ sexes; IMAT increased more with TAT in HIV+ vs. HIV- men (P<0.05 for slope interaction) but there were no significant differences in women. There were significant race by HIV interactions in AT distribution with more pronounced VAT differences in non-Hispanic white men and larger trunk SAT in African Americans HIV+ vs. HIV-. CONCLUSION: The AT distribution differed markedly in HIV+ vs. HIV- with limb and lower body SAT representing a smaller proportion of TAT in HIV+ in both sexes and IMAT representing a larger proportion of TAT in HIV+ vs. HIV- men.

Truncal fat in relation to total body fat: influences of age, sex, ethnicity and fatness.

OBJECTIVE: To investigate the influence of age, sex, ethnicity and total fatness on central obesity in four ethnic populations. DESIGN: Cross-sectional analysis of study subjects enrolled from 1993 to 2005. SUBJECTS: A multi-ethnic (Caucasian (CA), African-American (AA), Hispanic-American (HA) and Asian (As)) convenience sample of 604 men and 1192 women (aged 18-96 years, body mass index 15.93-45.80 kg/m(2)). MEASUREMENTS: Total body fat (TBF) and truncal fat were measured by dual-energy X-ray absorptiometry. General linear regression models were used to test for independent associations with log(10)-transformed truncal fat. RESULTS: For all ethnicities, men had a lower percent body fat and more truncal fat than women. Log(10-)transformed truncal fat increased with TBF approximately as a square root function. At older ages, there was a greater amount of truncal fat in CA, HA and As men (approximately 0.20-0.25 kg/decade) with the effect more pronounced in AA men ( approximately 0.33 kg/decade). For women, the increment of truncal fat per decade was reduced in CA and AA women (approximately 0.07 kg) compared with As and HA women (approximately 0.33 kg). Adjusted for mean values of covariates in our sample, AA had less truncal fat than As. CONCLUSION: The accumulation of truncal fat is strongly related to age, ethnicity and total fatness in both men and women.

Intermuscular adipose tissue rivals visceral adipose tissue in independent associations with cardiovascular risk.

BACKGROUND: The metabolic implications of intermuscular adipose tissue (IMAT) are poorly understood compared to those of visceral adipose tissue (VAT) even though the absolute quantities of both depots are similar in many individuals. OBJECTIVE: The aim was to determine the independent relationship between whole-body IMAT and cardiovascular risk factor parameters. DESIGN: Whole body magnetic resonance imaging (MRI) was used to quantify total skeletal muscle (SM), total adipose tissue (TAT) of which IMAT, defined as the AT visible by MRI within the boundary of the muscle fascia, is a sub-component. Fasting serum measures (n=262) of glucose, total cholesterol (T-Chol), high-density lipoprotein cholesterol (HDL-Chol), triglycerides (TG), protein bound glucose (PBG, n=206) and insulin (n=119) were acquired in healthy African-American (AA, n=78) and Caucasian (Ca, n=109) women (body mass index (BMI) 26.5+/-5.7 kg/m(2); 44.4+/-16.4 years) and men (39 AA, 62 Ca; BMI 25.6+/-3.5 kg/m(2); 45.6+/-17.4 years). General linear models identified the independent effects of IMAT after covarying for SM, VAT, TAT, race, sex and two-way interactions. RESULTS: Significant independent associations were observed for IMAT with glucose (P<0.001), PBG (P<0.001) and T-Chol (P<0.05). The association of IMAT with cholesterol differed by race in such a manner that for a unit increase in IMAT, T-Chol increased more rapidly in Ca compared to AA (P<0.05). TG, HDL-Chol and insulin had no independent association with IMAT. CONCLUSION: The strong independent associations of IMAT with fasting glucose and PBG suggest that IMAT may be related to glucose metabolism; however, IMAT is also associated with T-Chol in Ca.

Visceral adipose tissue: relationships between single slice areas at different locations and obesity-related health risks.

BACKGROUND: Visceral adipose tissue (VAT) is widely recognized as conveying the highest health risk in humans among the currently measurable adipose tissue compartments. A recent study indicated that the traditionally measured VAT area at L(4)-L(5) is not the VAT area with the highest correlation with total VAT volume. At present, it is unknown whether the area with the highest correlation is also the most strongly associated with obesity-related health risk. OBJECTIVE: The study aim was to establish which VAT slice area(s) are most strongly associated with obesity-related health risk indicators. DESIGN: The subjects were a convenience sample of healthy adults who completed whole-body magnetic resonance imaging (MRI) scans. The correlations, with appropriate adjustments, were examined between individual MRI slice VAT areas and fasting serum/plasma triglycerides (TG), high-density lipoprotein cholesterol (HDL), glucose, insulin and blood pressure. RESULTS: The sample consisted of 283 healthy men (age (mean+/-s.d.) 41.9+/-15.8 years; BMI, 26.0+/-3.2 kg/m(2); VAT, 2.7+/-1.8 L) and 411 women (age, 48.1+/-18.7 years; BMI 27.0+/-5.4 kg/m(2); VAT, 1.7+/-1.2 L). After adjusting for age, race, menopause status, scan position and specific blood analysis laboratory, VAT area at L(4)-L(5) had lower correlations with most metabolic risk factors including serum/plasma TG, HDL, glucose, insulin and blood pressure than VAT volume in both men and women. The VAT areas 10 and 15 cm above L(4)-L(5) in men had higher or equal correlations with health risk measures than VAT volume. In women, the VAT area 5 cm above or below L(4)-L(5) and total VAT volume had similar correlations with health risk measures. CONCLUSIONS: An appropriately selected single slice VAT area is an equally reliable phenotypic marker of obesity-related health risk as total VAT volume. However, in both men and women the VAT slice area at the traditional L(4)-L(5) level is not the best marker of obesity-related health risk.

Human adenovirus-36 is associated with increased body weight and paradoxical reduction of serum lipids.

BACKGROUND: Human adenovirus-36 (Ad-36) increases adiposity and paradoxically lowers serum cholesterol and triglycerides in chickens, mice, and non-human primates. The role of Ad-36 in human obesity is unknown. OBJECTIVES: To determine the prevalence of Ad-36 antibodies in obese and nonobese humans. To evaluate the association of Ad-36 antibodies with body mass index (BMI) and serum lipids. DESIGN: Cohort study. Volunteers from obesity treatment programs, communities, and a research study. SUBJECTS: Obese and nonobese volunteers at the University of Wisconsin, Madison, WI, and the Bowen Center, Naples, Florida. Obese and thin volunteer research subjects and 89 twin pairs at Columbia University, New York. INTERVENTIONS: Study 1: 502 subjects; serum neutralization assay for antibodies to Ad-2, Ad-31, Ad-36, and Ad-37; serum cholesterol and triglycerides assays. Study 2: BMI and %body fat in 28 twin pairs discordant for Ad-36 antibodies. MAIN OUTCOME MEASURES: Presence of antibodies to adenoviruses, BMI, serum cholesterol and triglycerides levels. RESULTS: Significant (P < 0.001) association of obesity and positive Ad-36 antibody status, independent of age, sex, and collection site. Ad-36 antibodies in 30% of obese, 11% of nonobese. Lower serum cholesterol and triglycerides (P < 0.003) in Ad-36 antibody-positive vs -negative subjects. Twin pairs: antibody-positive twins had higher BMIs (24.5+/-5.2 vs 23.1+/-4.5 kg/m2, P < 0.03) and %body fat (29.6+/-9.5% vs 27.5+/-9.9%, P < 0.04). No association of Ad-2, Ad-31, or Ad-37 antibodies with BMI or serum lipids. CONCLUSIONS: Ad-36 is associated with increased body weight and lower serum lipids in humans. Prospective studies are indicated to determine if Ad-36 plays a role in the etiology of human obesity.

Relationship between serum resistin concentrations and insulin resistance in nonobese, obese, and obese diabetic subjects.

Early reports suggested that resistin is associated with obesity and insulin resistance in rodents. However, subsequent studies have not supported these findings. To our knowledge, the present study is the first assessment in human subjects of serum resistin and insulin sensitivity by the insulin clamp technique. Thirty-eight nonobese subjects [age, 23 +/- 4 yr; body mass index (BMI), 25.4 +/- 4.3 kg/m(2)], 12 obese subjects (age, 54 +/- 8 yr; BMI, 33.0 +/- 2.5 kg/m(2)), and 22 obese subjects with type 2 diabetes (age, 59 +/- 7 yr; BMI, 34.0 +/- 2.4 kg/m(2)) were studied. Serum resistin concentrations were not different among nonobese (4.1 +/- 1.7 ng/ml), obese (4.2 +/- 1.6 ng/ml), and obese diabetic subjects (3.7 +/- 1.2 ng/ml), and were not significantly correlated to glucose disposal rate during a hyperinsulinemic glucose clamp across groups. Serum resistin was, however, inversely related to insulin sensitivity in nonobese subjects only (r = -0.35; P = 0.05), although this association was lost after adjusting for percent body fat. Serum resistin was not related to percent fat, BMI, or fat cell size. A strong correlation was observed between serum resistin and resistin mRNA expression from abdominal sc adipose tissue in a separate group of obese subjects (r = 0.62; P < 0.01; n = 56). Although the exact function of resistin is unknown, we demonstrated only a weak relationship between resistin and insulin sensitivity in nonobese subjects, indicating that resistin is unlikely to be a major link between obesity and insulin resistance in humans.

Sleeping metabolic rate in relation to body mass index and body composition.

OBJECTIVES: To determine whether patterns of sleeping metabolic rate (SMR) are altered in obesity. Specifically to determine the relationship between changes in SMR and body weight, body mass index (BMI, kg/m(2)), and fat-free mass (FFM); and to compare resting metabolic rate (RMR) with SMR during different periods of sleep. SUBJECTS: Eighteen healthy, pre-menopausal, obese (BMI >30, n=9) and non-obese (BMI <30, n=9), female subjects (six Caucasians and 12 African-Americans), with an average age of 36 y (range 22-45). MEASUREMENTS: Total energy expenditure (TEE or 24 h EE), metabolic rate (MR), SMR (minimum, average and maximum) and resting metabolic rate (RMR) or resting energy expenditure (REE) measured by human respiratory chamber, and external mechanical work measured by a force platform within the respiratory chamber. Physical activity index (PAL) was derived as TEE/REE. Body composition was determined by dual-energy X-ray absorptiometry (DXA). RESULTS: SMR decreased continuously during sleep and reached its lowest point just before the subject was awakened in the morning by the research staff. Although averages for RMR and SMR were similar, RMR was lower than SMR at the beginning of the sleeping period and higher than SMR in the morning hours. The rate of decrease in SMR was faster with increasing body weight (-0.829, P<0.0001), BMI (correlation factor -0.896, P<0.0001) and FFM (-0.798, P=0.001). The relationship between the slope of SMR decrease and BMI (y=-5 x 10(-6)x(2)+0.0002x-0.0028) is highly significant, with a P-value of <0.0001 and r(2) value of 0.9622. CONCLUSIONS: The rate of decline in metabolic rate during sleep is directly related to body weight, BMI and FFM. Average SMR tends to be lower than RMR in obese subjects and higher than RMR in non-obese subjects.

Impaired insulin action in subcutaneous adipocytes from women with visceral obesity.

Visceral obesity is associated with resistance to the antilipolytic effect of insulin in vivo. We investigated whether subcutaneous abdominal and gluteal adipocytes from viscerally obese women exhibit insulin resistance in vitro. Subjects were obese black and white premenopausal nondiabetic women matched for visceral adipose tissue (VAT), total adiposity, and age. Independently of race and adipocyte size, increased VAT was associated with decreased sensitivity to insulin's antilipolytic effect in subcutaneous abdominal and gluteal adipocytes. Absolute lipolytic rates at physiologically relevant concentrations of insulin or the adenosine receptor agonist N(6)-(phenylisopropyl)adenosine were higher in subjects with the highest vs. lowest VAT area. Independently of cell size, abdominal adipocytes were less sensitive to the antilipolytic effect of insulin than gluteal adipocytes, which may partly explain increased nonesterified fatty acid fluxes in upper vs. lower body obese women. Moreover, increased VAT was associated with decreased responsiveness, but not decreased sensitivity, to insulin's stimulatory effect on glucose transport in abdominal adipocytes. These data suggest that insulin resistance of subcutaneous abdominal and, to a lesser extent, gluteal adipocytes may contribute to increased systemic lipolysis in both black and white viscerally obese women.

Weight loss in postmenopausal obesity: no adverse alterations in body composition and protein metabolism.

We sought to determine if decrements in the mass of fat-free body mass (FFM) and other lean tissue compartments, and related changes in protein metabolism, are appropriate for weight loss in obese older women. Subjects were 14 healthy weight-stable obese (BMI > or =30 kg/m(2)) postmenopausal women >55 yr who participated in a 16-wk, 1, 200 kcal/day nutritionally complete diet. Measures at baseline and 16 wk included FFM and appendicular lean soft tissue (LST) by dual-energy X-ray absorptiometry; body cell mass (BCM) by (40)K whole body counting; total body water (TBW) by tritium dilution; skeletal muscle (SM) by whole body MRI; and fasting whole body protein metabolism through L-[1-(13)C]leucine kinetics. Mean weight loss (+/-SD) was 9.6+/-3.0 kg (P<0.0001) or 10.7% of initial body weight. FFM decreased by 2.1+/-2.6 kg (P = 0.006), or 19.5% of weight loss, and did not differ from that reported (2.3+/-0.7 kg). Relative losses of SM, LST, TBW, and BCM were consistent with reductions in body weight and FFM. Changes in [(13)C]leucine flux, oxidation, and synthesis rates were not significant. Follow-up of 11 subjects at 23.7 +/-5.7 mo showed body weight and fat mass to be below baseline values; FFM was nonsignificantly reduced. Weight loss was accompanied by body composition and protein kinetic changes that appear appropriate for the magnitude of body mass change, thus failing to support the concern that diet-induced weight loss in obese postmenopausal women produces disproportionate LST losses.

Fat distribution and health in obesity.

Although independent associations of visceral fat with the insulin resistance syndrome were previously reported in obese women, the importance of truncal subcutaneous fat in this syndrome is controversial. The method by which the various fat depots are measured may be the reason for the underlying controversy. In the past five years, we have used various methods to measure visceral versus subcutaneous fat distribution in Caucasian (C) and African-American (AA) women and have related it to insulin sensitivity (SI) and to blood lipids, particularly fasting serum triglyceride levels (TG). Elevated TG levels in obese women were best predicted by an increased amount of visceral fat, whereas the amounts of truncal and peripheral subcutaneous fat did not have an impact on them. These results were confirmed, regardless of the method used to measure the fat depots. Insulin resistance (low SI) in obese women was predicted by both an increase of visceral and of upper-body (truncal) subcutaneous fat. However, measurements of the entire visceral and truncal subcutaneous fat volumes may be needed to confirm this latter association.

Systemic resistance to the antilipolytic effect of insulin in black and white women with visceral obesity.

This study was designed to determine the role of visceral adipose tissue (VAT) accumulation in systemic fat metabolism and to compare this in black and white women who differ in their manifestations of upper body obesity. Systemic glycerol and free fatty acid (FFA) turnover rates (rates of appearance, Ra) were measured in the basal state and during a pancreatic euglycemic clamp in nondiabetic, premenopausal, obese black and white women with a wide range of VAT accumulation. The slopes of the regression equations predicting basal and insulin-suppressed RaGlycerol and RaFFA from VAT area, age, and fat mass or fat-free mass did not significantly differ between black and white women. VAT area was the best predictor of the %-suppressed RaGlycerol and RaFFA during the pancreatic clamp (partial r = 0.76, P < 0.0001 and partial r = 0.60, P < 0.05, respectively). Basal R(a)Glycerol, but not RaFFA, was lower in black than in white women (P < 0.05). During the clamp, black women showed greater insulin suppression of RaGlycerol than of RaFFA (P < 0.0001) and greater insulin suppression of RaGlycerol (P < 0. 05) but similar suppression of RaFFA compared with white women. These differences were independent of age, fat mass, or fat-free mass and were partly explained by a lower VAT in black women. Thus, in both races, VAT accumulation was associated with systemic resistance to the antilipolytic effect of insulin and, in obese black women, systemic lipolysis measured as glycerol turnover rate was more responsive to insulin suppression than were systemic FFA turnover rates.

Identification and functional analysis of novel human melanocortin-4 receptor variants.

Inactivation of the melanocortin-4 receptor (MC4-R) by gene-targeting results in mice that develop maturity-onset obesity, hyperinsulinemia, and hyperglycemia. These phenotypes resemble common forms of human obesity, which are late-onset and frequently accompanied by NIDDM. It is not clear whether sequence variation of the MC4-R gene contributes to obesity in humans. Therefore, we examined the human MC4-R gene polymorphism in 190 individuals ascertained on obesity status. Three allelic variants were identified, including two novel ones, Thr112Met and Ile137Thr. To analyze possible functional alterations, the variants were cloned and expressed in vitro and compared with the wild-type receptor. One of the novel variants, Ile137Thr, identified in an extremely obese proband (BMI 57), was found to be severely impaired in ligand binding and signaling, raising the possibility that it may contribute to development of obesity. Furthermore, our results also suggest that sequence polymorphism in the MC4-R coding region is unlikely to be a common cause of obesity in the population studied, given the low frequency of functionally significant mutations.

Insulin sensitivity and serum triglyceride level in obese white and black women: relationship to visceral and truncal subcutaneous fat.

Although independent associations of visceral fat with the insulin resistance syndrome were previously reported in obese women, the importance of truncal subcutaneous fat with regard to insulin sensitivity is still controversial. We measured the insulin sensitivity index (S(I)), serum triglyceride (TG) level, and regional fat by two methods: (1) the sum of five truncal and four peripheral skinfolds (TrSUM and PerSUM) in 38 white and black obese nondiabetic premenopausal women, and (2) abdominal visceral (VFM) and subcutaneous fat mass (AbdSCFM) by a combination of magnetic resonance imaging (MRI) and dual x-ray absorptiometry (DXA) in a subset of 26 of these women. After adjusting for the total body fat mass, TrSUM and VFM were independently and negatively related to S(I) (n = 38, P < .012 and n = 26, P < .035, respectively), whereas PerSUM and AbdSCFM were not related (P > .50). Based on multiple regression modeling, TrSUM significantly predicted S(I) independently of the VFM (n = 26, P < .001). Black women had lower S(I) at all levels of TrSUM (n = 38, P = .061 for the slope and P = .03 for the intercept of the regression lines). After adjusting for the total body fat mass, only VFM showed an independent positive relation to serum TG, and race did not affect this relationship (n = 26, P < .001). In conclusion, (1) we confirmed the independent association of the VFM with insulin resistance and elevated TG in obese women; (2) the AbdSCFM measured by a combination of MRI and DXA did not show an independent association with S(I) in obese women; and (3) the independent association of TrSUM with S(I) suggests that truncal subcutaneous fat depots contribute to insulin resistance in obese women independently of the degree of visceral fat.

Measurement challenges and other practical concerns when studying massively obese individuals.

OBJECTIVE: To describe the measurement challenges faced and to evaluate the measurement quality obtained with massively obese individuals. METHOD: A cross-sectional analysis of 107 individuals with body mass indices (kg/m2) > or = 50 was conducted. Individuals had their body fat measured via bioimpedance analysis (BIA), their serum leptin levels measured via radioimmunoassay (RIA), and height and weight measured via both laboratory scales and self-report. RESULTS: Serum leptin appeared to be measured accurately, provided the serum was diluted prior to conducting the RIA. Difficulties remained, however, in evaluating what was an unusual or expected value of leptin among individuals this large. Measures of impedance appeared to provide reasonable ordinal indications of body fatness. However, currently available equations for converting measures of impedance to estimates of percent body fat were highly inaccurate. Self-reported height and weight were reasonably good proxies of measured height and weight among individuals who reported their height and weight. However, a substantial proportion were unable to provide estimates. DISCUSSION: The above results suggest there are substantial challenges when trying to obtain meaningful measurements regarding obesity-related variables among massively obese individuals. Other logistic challenges also are discussed. It is hoped future research is directed at overcoming some of these challenges.

Resting metabolic rate in obese, premenopausal black women.

In the United States, obesity is more prevalent in black than in non-Hispanic white women. Because low resting metabolic rate (RMR) has been suggested as a risk factor for weight gain, we compared RMR in 22 black and 20 white obese [body mass index (BMI; in kg/m2) range: 28.9-48.6 and 26.9-44.1, respectively], weight-stable, premenopausal, nondiabetic women. RMR was measured on two or three different occasions within a 1-wk period. The black and white groups did not differ significantly in age, degree of fitness, BMI, fat mass, or fat-free mass (FFM). In each group, RMR was predicted independently by FFM but not by age, degree of fitness, body fat mass, or body fat distribution. The slopes of the equations predicting RMR from FFM in black and white groups were not significantly different. However, the black women had significantly lower RMRs than the white women after adjustment for FFM measured by five body-composition models: dual-photon X-ray absorptiometry (DXA), hydrodensitometry, total body water, a three-compartment model, a four-compartment model, as well as for the absolute total-body potassium content as a measure of metabolically active FFM. By each analysis, the black women had significantly lower (P < 0.01) FFM-adjusted RMR than the white women; this difference ranged from 671 to 889 kJ/d depending on the body-composition method used to estimate FFM. This could contribute to the difference in the prevalence of obesity in the populations represented by these groups.

Obesity solutions: report of a meeting.

A workshop entitled "Obesity Solutions" was held on January 11, 1996, at St. Luke's-Roosevelt Hospital in New York City and was jointly sponsored by the St. Luke's-Roosevelt Obesity Research Center and the Nestlé R&D Center, Inc., of New Milford, Connecticut. The purpose of the workshop was to bring together experts from the research community and the pharmaceutical and food industries to address the epidemic of obesity in the United States and offer potential solutions. The following is a report of that meeting.