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.

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.

Body composition, not body weight, is related to cardiovascular disease risk factors and sex hormone levels in men.

To clarify the independent relationships of obesity and overweight to cardiovascular disease risk factors and sex steroid levels, three age-matched groups of men were studied: (i) 8 normal weight men, less than 15% body fat, by hydrostatic weighing; (ii) 16 overweight, obese men, greater than 25% body fat and 135-160% of ideal body weight (IBW); and (iii) 8 overweight, lean men, 135-160% IBW, but less than 15% fat. Diastolic blood pressure was significantly greater for the obese (mean +/- SEM, 82 +/- 2 mmHg) than the normal (71 +/- 2) and overweight lean (72 +/- 2) groups, as were low density lipoprotein levels (131 +/- 9 vs. 98 + 11 and 98 + 14 mg/dl), the ratio of high density lipoprotein to total cholesterol (0.207 +/- 0.01 vs. 0.308 +/- 0.03 and 0.302 +/- 0.03), fasting plasma insulin (22 +/- 3 vs. 12 +/- 1 and 13 +/- 2 microU/ml), and the estradiol/testosterone ratio (0.076 +/- 0.01 vs. 0.042 +/- 0.02 and 0.052 +/- 0.02); P less than 0.05. Estradiol was 25% greater for the overweight lean group (40 +/- 5 pg/ml) than the obese (30 +/- 3 pg/ml) and normal groups (29 +/- 2 pg/ml), P = 0.08, whereas total testosterone was significantly lower in the obese (499 +/- 33 ng/dl) compared with the normal and overweight, lean groups (759 +/- 98 and 797 +/- 82 ng/dl). Estradiol was uncorrelated with risk factors and the estradiol/testosterone ratio appeared to be a function of the reduced testosterone levels in obesity, not independently correlated with lipid levels after adjustment for body fat content. Furthermore, no risk factors were significantly different between the normal and overweight lean groups. We conclude that (a) body composition, rather than body weight per se, is associated with increased cardiovascular disease risk factors; and (b) sex steroid alterations are related to body composition and are not an independent cardiovascular disease risk factor.

Independent effects of obesity and insulin resistance on postprandial thermogenesis in men.

The putative blunted thermogenesis in obesity may be related to insulin resistance, but insulin sensitivity and obesity are potentially confounding factors. To determine the independent effects of obesity and insulin resistance on the thermic effect of food, at rest and after exercise, lean and obese men were matched at two levels of insulin sensitivity determined by insulin-stimulated glucose disposal (milligrams per kilogram fat-free mass [FFM] per minute) during the euglycemic, hyperinsulinemic (40 mU/m2.min) clamp: 5.4 mg/kg FFM for the lean and obese groups with low insulin sensitivity, and 8.1 mg/kg FFM for the groups with high insulin sensitivity. The two lean groups were matched for percent fat (approximately 15 +/- 1% fat), as were the two obese groups (approximately 33 +/- 2% fat). Energy expenditure was measured for 3 h in the fasting state and for 3 h after a 720-kcal mixed meal, each at rest and immediately after 1 h of cycling at 100 W. The thermic effect of food (TEF) was calculated as the postprandial minus fasting energy expenditure (kcal/3 h) during rest and after exercise. During rest, TEF was blunted by both obesity (24 +/- 5 and 34 +/- 6 kcal/3 h for obese groups with low and high insulin sensitivity vs. 56 +/- 6 and 74 +/- 6 kcal/3 h for the lean groups with low and high insulin sensitivity; P less than 0.01 lean vs. obese) and insulin resistance (insulin-resistant less than insulin-sensitive, at both levels of obesity; P less than 0.01). After exercise, TEF was also impaired in the obese (47 +/- 6 and 44 +/- 5 kcal/3 h for the insulin-resistant and -sensitive groups) and in the lean insulin-resistant (55 +/- 5 kcal/3 h), compared with the lean insulin-sensitive men (71 +/- 3 kcal/3 h), P less than 0.01. Compared with rest, TEF after exercise was improved, but not normalized, in both obese groups (P less than 0.05), but unchanged in the lean groups. These results suggest that both insulin resistance and obesity are independently associated with impaired TEF at rest, but the responsiveness of thermogenesis to exercise before a meal is related to the obese state and not independently to insulin resistance per se.

Visceral fat and race-dependent health risks in obese nondiabetic premenopausal women.

Our previous finding that a waist-to-hip ratio (WHR) >0.85 was not associated with similar health risks in black, compared with white, obese premenopausal non-diabetic women of similar fatness is attributed to either 1) a different relationship between WHR and visceral adiposity or 2) differences in the relationship between visceral adiposity and the metabolic abnormalities of obesity. We measured visceral (VAT) and subcutaneous adipose tissue (SCAT) areas at midwaist in 25 black and 25 white obese nondiabetic pre-menopausal women with similar BMI, percentage body fat, and wide range of WHR (0.7-0.95 for black women and 0.7-0.9 for white women) and then compared insulin sensitivity index (SI), glucose and insulin areas under the 2-h curve (AUCs) during an oral glucose tolerance test (OGTT), and blood lipids in the two groups before and after adjustments for total body and visceral adiposity. After adjusting for total body fat mass (FM), obese black women had significantly less VAT (by 32 cm2) and lower VAT/SCAT for any given WHR. The regression equations predicting the SI the glucose and insulin AUCs, and the triglyceride and HDL cholesterol levels from regional adipose tissue measurements (VAT, SCAT, or VAT/SCAT) and from total body fat (FM or percentage body fat) had slopes that were not significantly different for black and white women. LDL cholesterol levels were independently related to VAT in black but not in white women. The black women had a similar SI insulin AUC, and triglyceride levels but significantly lower glucose AUC and higher HDL cholesterol levels (P < 0.001), after adjusting for VAT and FM. Regression analysis of the pooled data showed that high VAT and high VAT/SCAT, but not SCAT, predicted lower SI higher glucose and insulin AUCs during OGTT, and higher triglyceride levels, independent of total adiposity. We conclude that while increases in VAT and VAT/SCAT adversely affect metabolism in both black and white obese premenopausal women, similar levels of total body and visceral adiposity are associated with different metabolic risk factors in these groups.

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.

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.

Effects of recombinant human insulin-like growth factor-I (rhIGF-I) on total and free IGF-I concentrations, IGF-binding proteins, and glycemic response in humans.

To examine the effects of repeated administration of recombinant human insulin-like growth factor-I (rhIGF-I) on IGF-I levels, free IGF-I pharmacokinetics, glycemic response, and IGF-binding proteins (IGFBP), we administered rhIGF-I (0.03 mg/kg iv bolus) to 12 healthy males each morning for 5 consecutive days. Serum was collected over 24 h on days 1 and 5 for measurement of total and free IGF-I, glucose, insulin, and IGFBP. Total IGF-I was measured by RIA after acid/ethanol extraction. Free IGF-I was separated from binding protein-complexed IGF-I using size exclusion high performance liquid chromatography before measurement by RIA. IGFBP were quantitated by optical densitometry of Western ligand blots. Total IGF-I increased significantly from 0-24 h after administration on day 1 (mean +/- SD, micrograms/L: 120 +/- 44 to 166 +/- 51, P = 0.0002) but did not increase significantly from 24 h on day 1 to 0 h on day 5 (166 +/- 51 to 178 +/- 62) or from 0-24 h on day 5 (178 +/- 62 to 209 +/- 89). The area under the total IGF-I concentration curve was greater on day 5 than day 1 (311 +/- 99 min.g/L vs. 249 +/- 77, P = 0.0001). There were no significant differences in free IGF-I concentration or pharmacokinetic parameters or in the degree or timing of hypoglycemia between days 1 and 5. Plasma insulin levels decreased significantly following rhIGF-I administration (day 1 baseline: 53 +/- 11 pmol/L, nadir: 18 +/- 6 pmol/L at 30 min, P = 0.003); day 5 baseline: 47 +/- 15 pmol/L, nadir: 16 +/- 8 pmol/L at 30 min, P = 0.0003. Western ligand blotting revealed the transient appearance of a 30-kilodalton band which migrates in a manner similar to IGFBP-1. This band was undetectable at baseline, peaked between 150 and 210 min after rhIGF-I administration, and diminished by 480-600 min. The response was similar on days 1 and 5. There were no substantial changes in the serum levels of any other IGFBP. In summary, repeated iv bolus administration of rhIGF-I increased the level of total circulating IGF-I without changing free IGF-I disposition or glycemic response. A 30-kilodalton IGFBP band, most likely IGFBP-1, appeared transiently following rhIGF-I administration, probably as a result of suppression of insulin levels. IGFBP-2, -3, and -4 were unaffected.

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.

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.

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.

Composition of weight loss in severely obese women: a new look at old methods.

Seven severely obese, outpatient dieters lost weight (mean +/- SEM, 14 +/- 1 kg), and the composition of weight lost was determined by six different models. Total body water (TBW), total body potassium (TBK), and body density, bone mineral content, and fat as determined by dual photon absorptiometry (DPA) were measured while subjects were weight-stable, before and after weight loss. Fat loss was calculated by three two-compartment models (2C-TBW, 2C-TBK, and hydrodensitometry [2C-HD]), one three-compartment model (HD with correction for water content of fat-free mass [FFM], 3C), and one four-compartment model (HD with correction for water and mineral content of FFM, 4C), and was measured directly by DPA. Mean composition of weight loss was similar for all models (mean weight lost as fat: 89% for DPA, 91.5% for 4C, 89% for 3C, 88.6% for 2C-HD, and 87% for 2C-TBW) except 2C-TBK (weight lost as fat, 66%). There was a much wider range of individual values for the 2C-TBW and 2C-TBK models (17% to 138% and 18% to 93%, respectively) than for the multicompartment models (63% to 112%) and DPA (76% to 107%). Almost opposite results were obtained for the same individual when using the 2C-TBK and 2C-TBW models. The discrepancy between these models was due to the inverse relationship between changes in TBW and TBK in the group as a whole (r = -.34, NS). In addition, TBK loss was found to be dependent on the initial level of hyperinsulinemia, calculated as the area under the 2-hour oral glucose tolerance curve.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of exercise training on insulin sensitivity and glucose metabolism in lean, obese, and diabetic men.

To clarify the impact of vigorous physical training on in vivo insulin action and glucose metabolism independent of the intervening effects of concomitant changes in body weight and composition and residual effects of an acute exercise session, 10 lean, 10 obese, and 6 diet-controlled type II diabetic men trained for 12 wk on a cycle ergometer 4 h/wk at approximately 70% of maximal O2 uptake (VO2max) while body composition and weight were maintained by refeeding the energy expended in each training session. Before and 4-5 days after the last training session, euglycemic hyperinsulinemic (40 mU.m2.min-1) clamps were performed at a plasma glucose of 90 mg/dl, combined with indirect calorimetry. Total insulin-stimulated glucose disposal (M) was corrected for residual hepatic glucose output. Body weight, fat, and fat-free mass (FFM) did not change with training, but cardiorespiratory fitness increased by 27% in all groups. Before and after training, M was lower for the obese (5.33 +/- 0.39 mg.kg FFM-1.min-1 pretraining; 5.33 +/- 0.46 posttraining) than for the lean men (9.07 +/- 0.49 and 8.91 +/- 0.60 mg.kg FFM-1.min-1 for pretraining and posttraining, respectively) and lower for the diabetic (3.86 +/- 0.44 and 3.49 +/- 0.21) than for the obese men (P less than 0.001). Insulin sensitivity was not significantly altered by training in any group, but basal hepatic glucose production was reduced by 22% in the diabetic men. Thus, when intervening effects of the last exercise bout or body composition changes were controlled, exercise training per se leading to increased cardiorespiratory fitness had no independent impact on insulin action and did not improve the insulin resistance in obese or diabetic men.

Weight cycling: more questions than answers.

Most men and women who attempt to lose weight will regain any weight that is lost. This cycle of weight loss and regain - referred to as weight cycling is a recurrent phenomenon for many patients. With the increased frequency of obesity and the increased prescriptions for weight-loss practices without an associated increase in the success of weight-loss maintenance, the concerns about weight cycling have grown. Recent literature has focused on the possible physiologic and psychologic hazards of weight cycling. Review of both human and animal studies indicates no conclusive evidence about harmful effects of weight cycling. Most studies show no adverse effects on metabolism. Some observational studies indicate an association between variations in body weight and increased morbidity and mortality but do not distinguish between voluntary and involuntary weight-loss events. The studies of psychologic hazards have been limited, and little convincing information is available. Without more compelling evidence of the risks of weight cycling, warnings overriding safe, effective weight-loss treatments for the obese are unwarranted. Appropriately designed studies are urgently needed to assess the long-term efficacy of procedures and treatments that promote weight-loss maintenance and to provide further analyses of the effects of weight cycling.

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.

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.

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.