Ceramide concentrations in liver, plasma, and very low-density lipoproteins of humans with severe obesity.

We investigated the relationships between ceramide species concentrations in liver, plasma and very low-density lipoproteins (VLDL) particles of humans with obesity as well as the relationships between hepatic fat content and hepatic ceramide concentrations and proportional distribution. Twenty-five obese (body mass index >35 kg/m2 ) adults participated in this study. Plasma, VLDL and hepatocellular ceramide concentrations were measured by liquid chromatography/tandem mass spectrometry. The proportionate distribution of measured ceramide species differed between liver, whole plasma and the VLDL fraction. We found significant, positive correlations between the proportion of C14:0, C18:0, C20:0 and C24:1 ceramide in the liver and whole plasma (γ = 0.491, p = 0.013; γ = 0.573, p = 0.003; γ = 0.479, p = 0.015; γ = 0.716, p = 0.00006; respectively). In contrast, only the proportional contribution of C24:1 ceramide correlated positively between VLDL and liver (γ = 0.425, p = 0.013). The percent hepatic fat correlated positively with the proportion of C18:1, C18:0 and C20:0 hepatic ceramides (γ = 0.415, p = 0.039; γ = 0.426, p = 0.034; γ = 0.612, p = 0.001; respectively), but not with total hepatic ceramide concentration. The proportions of whole plasma ceramide subspecies, especially C14:0, C18:0, C20:0 and C24:1chain length, are reflective of those of hepatic ceramide subspecies in obese humans; these appear to be markers of hepatic ceramide species composition.

Adipocyte Proteins and Storage of Endogenous Fatty Acids in Visceral and Subcutaneous Adipose Tissue in Severe Obesity.

OBJECTIVE: This study tested whether substrate concentrations or fatty acid storage proteins predict storage of endogenous lipids in visceral adipose tissue (VAT) and upper body subcutaneous adipose tissue (UBSQ) fat. METHODS: The day prior to surgery, 25 patients undergoing bariatric procedures received an infusion of autologous [1-14 C]triolein-labeled very low-density lipoprotein (VLDL) particles, and during surgery, they received a continuous [U-13 C]palmitate infusion/bolus [9,10-3 H]palmitate tracer. VAT and UBSQ fat were collected to measure VLDL-triglyceride (TG) storage, direct free fatty acid (FFA) storage rates, CD36 content, lipoprotein lipase (LPL), acyl-CoA synthetase, diacylglycerol acetyl-transferase, and glycerol-3-phosphate acyltransferase activities. RESULTS: Storage of VLDL-TG and FFA-palmitate in UBSQ and VAT was not different. Plasma palmitate concentrations correlated with palmitate storage rates in UBSQ and VAT (r = 0.46, P = 0.02 and r = 0.46, P = 0.02, respectively). In VAT, VLDL-TG storage was correlated with VLDL concentrations (r = 0.53, P < 0.009) and LPL (r = 0.42, P < 0.05). In UBSQ, VLDL-TG storage was correlated with LPL (r = 0.42, P < 0.05). CD36, acyl-CoA synthetase, glycerol-3-phosphate acyltransferase, and diacylglycerol acetyl-transferase were not correlated with VLDL-TG or palmitate storage. CONCLUSIONS: Adipose storage of VLDL-TG is predicted by VLDL-TG concentrations and LPL; FFA concentrations predict direct adipose tissue FFA storage rates.

Sex and Depot Differences in Palmitoleic Acid Content of Human Blood and Fat.

Palmitoleic acid has been classified as an insulin-sensitizing lipokine, but evidence for this from human studies has been inconsistent. We hypothesized that this is related to either the types of samples or conditions under which samples are collected. We measured plasma palmitoleic acid and total free fatty acids (FFA) using ultra-performance liquid chromatography in blood samples collected from 34 adults under a variety of conditions. We collected duplicate samples of adipose (n = 10), FFA (n = 9), and very low density lipoprotein triacylglycerol (VLDL-TAG) (n = 7) to measure the palmitoleic acid as a percentage of total fatty acids. We tested whether the percentage of palmitoleic acid was correlated with insulin resistance, as measured by homeostatic model of insulin resistance (HOMA-IR). Adipose stearoyl-coenzyme A desaturase 1 (SCD-1) protein was measured by capillary Western blotting. FFA-palmitoleic acid percentage increased as a function of total FFA and was greater (p < 0.005) in females than males. Adipose palmitoleic acid percentage was greater in females than males (p < 0.001), as was adipose SCD-1. Palmitoleic acid was greater in femoral fat than in abdominal fat in both females and males (p < 0.001), and correlated positively with HOMA-IR only in females. The test-retest reliability values for percentage palmitoleic acid were 7 ± 10% for adipose, 24 ± 26% for VLDL, and 53 ± 31% for FFA. Because FFA-palmitoleic acid percentage varies as a function of total FFA, investigators should re-evaluate how palmitoleic acid data is presented. The positive relationship between adipose palmitoleic acid and HOMA-IR in females suggests that it is not a potent insulin-sensitizing lipokine in humans.

Race affects the association of obesity measures with insulin sensitivity.

BACKGROUND: Race differences in body composition and fat distribution may in part explain the differences in insulin sensitivity and the disproportionate burden of type 2 diabetes in African Americans. OBJECTIVE: To determine if differences in body composition and fat distribution explain race differences in insulin sensitivity and identify obesity measures that were independently associated with insulin sensitivity. METHODS: Participants were 113 lean, overweight, and obese African-American and Caucasian-American adults without diabetes. Skeletal muscle insulin sensitivity was determined using a hyperinsulinemic-euglycemic clamp (SIClamp, insulin rate:120 mU/m2/min). Subcutaneous abdominal adipose tissue (SAAT), intra-abdominal adipose tissue (IAAT), and liver fat were measured by MRI; leg fat, total fat, and lean mass were measured by DXA. RESULTS: Race-by-adiposity interactions were significant in cross-sectional analyses utilizing multiple linear regression models for SIClamp (P < 0.05); higher BMI, fat mass, SAAT, leg fat, and liver fat were associated with lower SIClamp in Caucasian Americans but not African Americans. Race-by-IAAT interaction was not significant (P = 0.65). A central fat distribution (SAAT adjusted for leg fat) was associated with lower SIClamp in African Americans (ß = -0.45, SE = 0.11, P < 0.001) but not Caucasian Americans (ß = -0.42, SE = 0.30, P = 0.17). A peripheral fat distribution (leg fat adjusted for IAAT/SAAT) was associated with a higher SIClamp in African Americans (ß = 0.11, SE = 0.05, P = 0.02) but lower SIClamp in Caucasian Americans (ß = -0.28, SE = 0.14, P = 0.049). Lean mass was inversely associated with SIClamp in African Americans (ß = -0.05, SE = 0.03, P = 0.04) but not Caucasian Americans (ß = 0.08, SE = 0.05, P = 0.10) in the model for leg fat. CONCLUSIONS: Measures of overall adiposity were more strongly associated with SIClamp in Caucasian Americans, whereas body fat distribution and lean mass showed stronger correlations with SIClamp in African Americans. Insulin sensitivity may have a genetic basis in African Americans that is reflected in the pattern of body fat distribution. These findings suggest a race-specific pathophysiology of insulin resistance, which has implications for the prevention of diabetes and related cardiometabolic diseases.

Hepatic Fatty Acid Balance and Hepatic Fat Content in Humans With Severe Obesity.

OBJECTIVE: Nonalcoholic fatty liver disease can lead to hepatic inflammation/damage. Understanding the physiological mechanisms that contribute to excess hepatic lipid accumulation may help identify effective treatments. DESIGN: We recruited 25 nondiabetic patients with severe obesity scheduled for bariatric surgery. To evaluate liver export of triglyceride fatty acids, we measured very-low-density lipoprotein (VLDL)-triglyceride secretion rates the day prior to surgery using an infusion of autologous [1-14C]triolein-labeled VLDL particles. Ketone body response to fasting and intrahepatic long-chain acylcarnitine concentrations were used as indices of hepatic fatty acid oxidation. We measured intraoperative hepatic uptake rates of plasma free fatty acids using a continuous infusion of [U-13C]palmitate, combined with a bolus dose of [9,10-3H]palmitate and carefully timed liver biopsies. Total intrahepatic lipids were measured in liver biopsy samples to determine fatty liver status. The hepatic concentrations and enrichment from [U-13C]palmitate in diacylglycerols, sphingolipids, and acyl-carnitines were measured using liquid chromatography/tandem mass spectrometry. RESULTS: Among study participants with fatty liver disease, intrahepatic lipid was negatively correlated with VLDL-triglyceride secretion rates (r = -0.92, P = 0.01) but unrelated to hepatic free fatty acid uptake or indices of hepatic fatty acid oxidation. VLDL-triglyceride secretion rates were positively correlated with hepatic concentrations of saturated diacylglycerol (r = 0.46, P = 0.02) and sphingosine-1-phosphate (r = 0.44, P = 0.03). CONCLUSION: We conclude that in nondiabetic humans with severe obesity, excess intrahepatic lipid is associated with limited export of triglyceride in VLDL particles rather than increased uptake of systemic free fatty acids.

A High-Fat Compared with a High-Carbohydrate Breakfast Enhances 24-Hour Fat Oxidation in Older Adults.

Background: The ability to oxidize fat is associated with a lower risk of chronic metabolic disease. Preclinical data in mice showed that a high-fat "breakfast" increased 24-h fat oxidation relative to a high-carbohydrate breakfast. Objectives: The objectives of this study were to determine whether the timing of macronutrient intake in humans affects daily fuel utilization and to examine associations between fuel utilization and metabolic indexes. Methods: Participants were 29 healthy sedentary men and women (aged 55-75 y) with a body mass index (kg/m2) between 25 and 35. Participants were randomly assigned to receive either a high-fat breakfast (FB; 35% carbohydrate, 20% protein, 45% fat; n = 13) or a high-carbohydrate breakfast (CB; 60% carbohydrate, 20% protein, 20% fat; n = 16) for 4 wk while consuming a "neutral" lunch and dinner. Twenty-four-hour and postprandial respiratory quotients (RQs) were measured by whole-room indirect calorimetry. Insulin and glucose measures including insulin sensitivity were determined by an oral-glucose-tolerance test. Measures were taken at baseline and after the 4-wk intervention. Group-by-time interactions were determined by 2-factor repeated-measures mixed-model ANOVA. Pearson's correlation analyses were used to determine associations of 24-h RQs with metabolic measures after the intervention. Results: There was a significant group-by-time interaction for change in the 24-h RQ [FB (mean ± SD): 0.88 ± 0.02 to 0.86 ± 0.02; CB: 0.88 ± 0.02 for both; P < 0.05], breakfast RQ (FB: 0.88 ± 0.03 to 0.86 ± 0.03; CB: 0.89 ± 0.02 to 0.90 ± 0.02; P < 0.01), and lunch RQ (FB: 0.089 ± 0.03 to 0.85 ± 0.03; CB: 0.89 ± 0.03 for both; P < 0.01). In the CB group at follow-up, 24-h RQ was positively associated with fasting glucose (r = 0.66, P < 0.05), glucose area under the curve (AUC) (r = 0.51, P < 0.05), and insulin AUC (r = 0.52, P < 0.05) and inversely associated with insulin sensitivity (r = -0.51, P < 0.05). Conclusions: The macronutrient composition of breakfast affects substrate utilization throughout the day in older adults. The consumption of a high-fat, lower-carbohydrate breakfast may reduce the risk of metabolic disease. This trial was registered at www.clinicaltrials.gov as NCT03164200.

Acute Testosterone Deficiency Alters Adipose Tissue Fatty Acid Storage.

Context: Although the long-term effects of testosterone on adipose tissue lipid metabolism in men have been defined, the short-term regulation of these effects is not well understood. Objective: We examined the effects of acute testosterone withdrawal on subcutaneous abdominal and femoral adipose tissue fatty acid (FA) storage and cellular mechanisms. Design: This was a prospective, randomized trial. Setting: Mayo Clinic Clinical Research Unit. Patients or Participants: Thirty-two male volunteers ages 18 to 50 participated in these studies. Interventions: Volunteers were randomized to receive (1) no treatment (control), (2) injections (7.5 mg) of Lupron®, or (3) Lupron and testosterone (L+T) replacement for 49 days, resulting in 4 weeks of sex steroid suppression in the Lupron group. Main Outcome Measures: We measured body composition, fat cell size, adipose tissue meal FA and direct free FA storage, lipoprotein lipase (LPL), acyl coenzyme A synthetase (ACS), diacylglycerol acyltransferase activities, and CD36 content. Results: Compared with control and L+T groups, acute testosterone deficiency resulted in greater femoral adipose tissue meal FA storage rates, fasting and fed LPL activity, and ACS activity. Conclusions: These results suggest that in men, testosterone plays a tonic role in restraining FA storage in femoral adipose tissue via suppression of LPL and ACS activities. FA storage mechanisms in men appear sensitive to short-term changes in testosterone concentrations.

Contribution of very low-density lipoprotein triglyceride fatty acids to postabsorptive free fatty acid flux in obese humans.

OBJECTIVE: In the fasting state, plasma free fatty acids (FFA) are thought to derive almost exclusively from adipose tissue lipolysis. However, there are mixed reports as to whether the spillover of fatty acids (FA) from very low-density lipoprotein triglyceride (VLDL-TG) hydrolysis contributes significantly to the plasma FFA pool. Because substantial VLDL-TG fatty acid spillover into the plasma FFA pool would profoundly impact the interpretation of isotope dilution measures of FFA flux, we investigated the contribution of VLDL-TG spillover to plasma FFA appearance. MATERIALS/METHODS: Eighteen obese adults (15 women) participated in these studies. Each volunteer received a primed, continuous infusion of their own ex-vivo labeled ([1-(14)C]triolein) VLDL-TG and a continuous infusion of [U-(13)C]oleate (8 nmol · kg fat free mass(-1) · min(-1)) to measure VLDL-TG and FFA rate of appearance (Ra), respectively. The presence of (14)C-oleate in the plasma FFA-oleate pool was used to calculate the contribution of spillover from VLDL-TG-oleate to the plasma FFA-oleate Ra. RESULTS: The spillover rate of VLDL-TG-oleate into plasma FFA-oleate was 6 ± 2 µmol/min (7% ± 2% of [(14)C]oleate from VLDL-TG) and FFA-oleate flux was 240 ± 61 µmol/min. Thus, only 3% ± 1% of total plasma FFA-oleate appearance could be accounted for by VLDL-TG spillover. CONCLUSION: The contribution of VLDL-TG spillover to the total plasma FFA pool is negligible and will not materially affect the interpretation of FFA flux measures as an index of adipose tissue lipolysis.

Insulin sensitivity affects propensity to obesity in an ethnic-specific manner: results from two controlled weight loss intervention studies.

BACKGROUND: Risk for obesity differs with ethnicity/race and is associated with insulin sensitivity (SI), insulin responsiveness, and dietary glycemic load (GL). The objective of this study was to test the hypotheses that, 1) obesity-prone, normal weight, African-American (AA) women would be more insulin sensitive than BMI-matched, never overweight AA women; 2) increased adiposity over time would be associated with greater baseline SI and higher dietary GL in AA but not European-American (EA) women; and 3) increased adiposity over time would be predicted by SI in women with high but not low acute insulin response to glucose (AIRg). METHODS: Two controlled weight loss interventions were conducted involving overweight (BMI 25.0-29.9 kg/m2) premenopausal AA and EA women. The first included matching with normal-weight (BMI <25.0 kg/m2) controls following weight loss, and then comparing SI. The second included a 1-year follow-up of weight-reduced participants to identify predictors of change in %body fat. Main outcome measure in the first study was insulin sensitivity (SI) as assessed with intravenous glucose tolerance test (IVGTT), and in the second study was change in %fat, as assessed with DXA, over one year. AIRg was assessed during IVGTT, and free-living diet was determined by food record. RESULTS: In the first study, formerly overweight AA women were 43% more insulin sensitive than BMI-matched never overweight AA (P < 0.05). In the second study, SI was positively associated with change in %fat over 1 year only in AA women (P < 0.05) and women with high AIRg (P < 0.05). In addition, AA who were insulin sensitive and who consumed a higher GL diet tended to gain greater %fat (P = 0.086 for diet x SI interaction). In both studies, AA women had higher AIRg (P < 0.001) than EA women. CONCLUSIONS: Formerly overweight (obesity-prone) AA women were more insulin sensitive than never overweight AA women, a quality that may predispose to adiposity, particularly when combined with a high GL diet. This ethnicity/race-specific effect may be due to high insulin responsiveness among AA.

Insulin-mediated FFA suppression is associated with triglyceridemia and insulin sensitivity independent of adiposity.

CONTEXT: A central/visceral fat distribution and excess free fatty acid (FFA) availability are associated with dyslipidemia and insulin resistance. However, these two characteristics often coexist, making it difficult to detect the independent contributions of each. Whether FFA suppression is more closely linked to metabolic abnormalities is not clear. OBJECTIVE: The aim of the study was to examine the relationship between FFA suppression, body fat distribution, and fitness as contributors toward insulin resistance and hypertriglyceridemia. DESIGN: We measured systemic palmitate turnover using an iv infusion of [9,10-(3)H]palmitate; upper body sc adipose tissue (UBSQ) and visceral adipose tissue (VAT) with dual-energy x-ray absorptiometry and a single-slice abdominal computed tomography scan; fitness with a graded exercise treadmill test; and insulin sensitivity with both the iv glucose tolerance test (IVGTT) (SI(IVGTT)) and mixed meal tolerance test (SI(Meal)). SETTING: The study was conducted at a General Clinical Research Center. PARTICIPANTS: Baseline data were obtained from 140 elderly adults (age, 60-88 yr; 83 males) and 60 young adults (age, 18-31 yr; 31 males) who participated in a previously published trial assessing the effects of 2-yr supplementation of dehydroepiandrosterone or testosterone on body composition, glucose metabolism, and bone density. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURES: We measured fasting plasma triglyceride (TG) concentrations, SI(IVGTT), and SI(Meal). RESULTS: Using multivariate regression analysis, the strongest combined predictors of TG concentrations were VAT, postmeal nadir FFA concentrations, sex, and age. The best predictors of SI(IVGTT) were IVGTT nadir palmitate concentration, VAT, UBSQ fat, fitness, and age, whereas the best predictors of SI(Meal) were meal nadir palmitate concentration, UBSQ fat, fitness, and sex. CONCLUSIONS: FFA suppression is associated with both fasting TG concentrations and insulin sensitivity, independent of measures of adiposity.

Higher maternal gestational glucose concentration is associated with lower offspring insulin sensitivity and altered beta-cell function.

CONTEXT: Intrauterine exposure to elevated glucose concentrations may be a mediating factor in prenatal programming of offspring diabetes risk. However, studies examining the effects of maternal glucose concentration on measures of insulin sensitivity and ß-cell response in prepubertal children are limited. OBJECTIVE: We tested the hypothesis that maternal gestational glucose concentration would be inversely associated with children's insulin sensitivity independent of adiposity and positively associated with children's ß-cell response independent of adiposity and insulin sensitivity. DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional study of 21 children aged 5-10 yr in a clinical research setting. OUTCOMES MEASURED: Children's insulin sensitivity index and basal, static, dynamic, and total ß-cell response to glucose were determined by mathematical modeling using insulin, glucose, and C-peptide values after a liquid meal tolerance test. Children's percent body fat was determined by dual-energy x-ray absorptiometry. Maternal gestational glucose concentration for the target pregnancy was determined after a 50-g, 1-h oral glucose challenge test at 24-28 wk gestation. RESULTS: Maternal glucose concentration was significantly, inversely associated with children's insulin sensitivity, independent of percent fat and ethnicity (P <0.05). A significant, positive association was observed for maternal glucose concentration with static ß-cell response, independent of percent fat and insulin sensitivity (P < 0.05). CONCLUSIONS: Maternal gestational glucose concentration was significantly associated with offspring insulin sensitivity and ß-cell response independent of adiposity. These results suggest that maternal glucose may program the fetus both at the pancreas and at the level of insulin target tissues such as skeletal muscle and liver.

Maternal glucose concentration during pregnancy predicts fat and lean mass of prepubertal offspring.

OBJECTIVE: Intrauterine exposure to high maternal glucose is associated with excess weight gain during childhood, but it is not clear whether the excess weight represents increased fat or lean mass. The purpose of this study was to examine the relationship between maternal glucose concentrations during pregnancy and offspring body composition. A secondary goal was to examine whether the association between maternal glucose and children's body fat was independent of energy intake, energy expenditure, or physical activity. RESEARCH DESIGN AND METHODS: Children aged 5-10 years and their biological mothers (n = 27) were recruited. Maternal glucose concentration 1 h after a 50-g oral glucose load, used to screen for gestational diabetes mellitus at 24-28 weeks gestation, was retrieved from medical records. Children underwent dual-energy X-ray absorptiometry to measure body composition, indirect calorimetry to measure resting energy expenditure (REE), accelerometry to measure physical activity, and three 24-h diet recalls to measure energy intake. RESULTS: Maternal glucose concentration during pregnancy was positively associated with children's lean mass (P < 0.05) and adiposity (fat mass adjusted for lean mass; P < 0.05). The association between maternal glucose and children's adiposity was independent of children's REE, percent of time spent physically active, and energy intake (P < 0.001). CONCLUSIONS: Intrauterine exposure to relatively high maternal glucose is associated with greater lean mass and adiposity among prepubertal offspring. Further research is needed to examine the mechanisms by which maternal glucose concentrations during pregnancy influence children's body composition.

Self-reported low vitality, poor mental health, and low dietary restraint are associated with overperception of physical exertion.

Objective. We investigated whether perceived exertion, in comparison to the physiological response to exercise, was associated with self-reported vitality, mental health, and physical function during daily activities, or weight control behaviors. Design. Weight-reduced, formerly overweight women (n = 126, aged 22-46 years), completed health and dietary control questionnaires, and underwent a treadmill-walking task while heart rate, ventilation, respiratory exchange ratio, and ratings of perceived exertion were recorded. Results. Overperception of exertion (perceived exertion physiological exertion) was inversely associated with vitality (r = -0.190, P < .05), mental health (r = -0.188, P < .05), and dietary control (r values range -0.231 to -0.317, P < .05). In linear regression modeling, vitality or mental health, and cognitive dietary restraint were independently associated with accuracy of perceived exertion, independent of age, ethnicity, and engagement in exercise during weight loss. Each model explained 7%-8% of the variance in accuracy of perceived exertion. Conclusion. Women with low vitality or poor mental health, and poor dietary control may overperceive exertion. Such overperception may be a barrier to engage in physical activity and thus increase susceptibility to weight gain.

Vitamin D intake is associated with insulin sensitivity in African American, but not European American, women.

BACKGROUND: The prevalence of type 2 diabetes is higher among African Americans (AA) vs European Americans (EA), independent of obesity and other known confounders. Although the reason for this disparity is not known, it is possible that relatively low levels of vitamin D among AA may contribute, as vitamin D has been positively associated with insulin sensitivity in some studies. The objective of this study was to test the hypothesis that dietary vitamin D would be associated with a robust measure of insulin sensitivity in AA and EA women. METHODS: Subjects were 115 African American (AA) and 137 European American (EA) healthy, premenopausal women. Dietary intake was determined with 4-day food records; the insulin sensitivity index (SI) with a frequently-sampled intravenous glucose tolerance test and minimal modeling; the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) with fasting insulin and glucose; and body composition with dual-energy X-ray absorptiometry. RESULTS: Vitamin D intake was positively associated with SI (standardized beta = 0.18, P = 0.05) and inversely associated with HOMA-IR (standardized beta = -0.26, P = 0.007) in AA, and the relationships were independent of age, total body fat, energy intake, and % kcal from fat. Vitamin D intake was not significantly associated with indices of insulin sensitivity/resistance in EA (standardized beta = 0.03, P = 0.74 and standardized beta = 0.02, P = 0.85 for SI and HOMA-IR, respectively). Similar to vitamin D, dietary calcium was associated with SI and HOMA-IR among AA but not EA. CONCLUSIONS: This study provides novel findings that dietary vitamin D and calcium were independently associated with insulin sensitivity in AA, but not EA. Promotion of these nutrients in the diet may reduce health disparities in type 2 diabetes risk among AA, although longitudinal and intervention studies are required.

Dietary calcium intake is associated with less gain in intra-abdominal adipose tissue over 1 year.

Calcium intake is reported to enhance weight loss with a preferential loss in trunk fat. Discrepant findings exist as to the effects of calcium intake on longitudinal changes in total fat mass and central fat deposition. Therefore, the purpose of this study was to determine associations between dietary calcium intake and 1-year change in body composition and fat distribution, specifically intra-abdominal adipose tissue (IAAT). A total of 119 healthy, premenopausal women were evaluated at baseline and 1 year later. Average dietary calcium was determined via 4-day food records. Total fat was determined by dual-energy X-ray absorptiometry (DXA) and subcutaneous abdominal adipose tissue (SAAT) and IAAT by computed tomography. Over the study period, participants' reported daily calcium and energy intakes were 610.0 ± 229.9 mg and 1,623.1 ± 348.5 kcal, respectively. The mean change in weight, total fat, IAAT, and SAAT was 4.9 ± 4.4 kg, 5.3 ± 4.0 kg, 7.7 ± 19.5 cm(2), and 49.3 ± 81.1 cm(2), respectively. Average calcium intake was significantly, inversely associated with 1-year change in IAAT (standardized ß: -0.23, P < 0.05) after adjusting for confounding variables. For every 100 mg/day of calcium consumed, gain in IAAT was reduced by 2.7 cm(2). No significant associations were observed for average calcium intake with change in weight, total fat, or SAAT. In conclusion, dietary calcium intake was significantly associated with less gain in IAAT over 1 year in premenopausal women. Further investigation is needed to verify these findings and determine the calcium intake needed to exert beneficial effects on fat distribution.

Glucose metabolism and diet predict changes in adiposity and fat distribution in weight-reduced women.

Among obesity-prone individuals, metabolic state may interact with diet in determining body composition. We tested the hypotheses that, among 103 weight-reduced women over 1 year, (i) insulin sensitivity would be positively associated with change in %fat; (ii) this association would be modulated by dietary glycemic load (GL); and (iii) changes in fat distribution would be related to indexes of glucose metabolism. Insulin sensitivity, glucose effectiveness, fasting and postchallenge insulin and glucose, and glucose tolerance were assessed during intravenous glucose tolerance test (IVGTT). Changes in %fat and fat distribution were examined using dual-energy X-ray absorptiometry and computed tomography. Dietary GL was assessed on 67 women using food records. On average, women showed a +5.3 +/- 3.0% change in %fat over 1 year, with the magnitude of this change being greater in relatively insulin sensitive women (+6.0 +/- 0.4%, mean +/- s.e.m.) than in relatively insulin resistant women (+4.4 +/- 0.4 kg; P < 0.05). Women who were relatively insulin sensitive and who consumed a higher GL diet showed a +6.8 +/- 0.7% change in %fat, which was greater than those who were less insulin sensitive, regardless of diet (P < 0.05), but did not differ from women who were relatively insulin sensitive and who consumed a lower GL diet (P = 0.105). Changes in intra-abdominal and deep subcutaneous abdominal fat were inversely associated with the postchallenge decline in serum glucose. In conclusion, greater insulin sensitivity may predispose to adiposity among weight reduced women, an effect that may be ameliorated by a lower GL diet. The potential association between indexes of glucose disposal and changes in fat distribution warrants further study.

Ethnicity-specific anthropometric predictors of metabolic risk in women.

OBJECTIVE: The objective of this study was to determine associations of anthropometric measures of thigh and abdominal adipose tissue with metabolic risk factors, and whether these associations differed with ethnicity. We hypothesized that thigh circumference (ThC) would have an independent favorable association with insulin sensitivity, lipids, and blood pressure, whereas waist circumference (WC) would have an independent deleterious association with these variables in both African Americans (AA) and European Americans (EA). METHODS: Subjects were 228 healthy, overweight, premenopausal AA and EA women. Insulin sensitivity was assessed by intravenous glucose tolerance test and minimal modeling. Simple relationships between anthropometric measures and risk factors were determined by Pearson correlation analysis. Partial correlation coefficients were determined for circumference measures adjusted for thigh and abdominal skinfolds to differentiate relationships between thigh and abdominal subcutaneous fat from thigh muscle and deeper abdominal fat, respectively. RESULTS: In EA but not AA, ThC was positively associated with insulin sensitivity, independent of thigh skinfold. In both EA and AA, ThC was associated with a desirable lipid profile. In AA but not EA, WC was associated with lower insulin sensitivity and a less desirable metabolic profile. CONCLUSION: Results suggest that thigh muscle (ThC adjusted for thigh skinfold) may be metabolically protective in EA but not AA. In contrast, WC was a better indicator of insulin sensitivity and metabolic health in AA. Further investigation is needed to verify the association between thigh muscle and metabolic health, and to probe the reason for the observed ethnic specificity of the associations between anthropometric measures and metabolic risk factors.

Associations among body size dissatisfaction, perceived dietary control, and diet history in African American and European American women.

European American (EA) women report greater body dissatisfaction and less dietary control than do African American (AA) women. This study investigated whether ethnic differences in dieting history contributed to differences in body dissatisfaction and dietary control, or to differential changes that may occur during weight loss and regain. Eighty-nine EA and AA women underwent dual-energy X-ray absorptiometry to measure body composition and completed questionnaires to assess body dissatisfaction and dietary control before, after, and one year following, a controlled weight-loss intervention. While EA women reported a more extensive dieting history than AA women, this difference did not contribute to ethnic differences in body dissatisfaction and perceived dietary control. During weight loss, body satisfaction improved more for AA women, and during weight regain, dietary self-efficacy worsened to a greater degree for EA women. Ethnic differences in dieting history did not contribute significantly to these differential changes. Although ethnic differences in body image and dietary control are evident prior to weight loss, and some change differentially by ethnic group during weight loss and regain, differences in dieting history do not contribute significantly to ethnic differences in body image and dietary control.

Insulin sensitivity in African-American and white women: association with inflammation.

Whether the contribution of inflammation to risk for chronic metabolic disease differs with ethnicity is not known. The objective of this study was to determine: (i) whether ethnic differences exist in markers of inflammation and (ii) whether lower insulin sensitivity among African Americans vs. whites is due to greater inflammatory status. Subjects were African-American (n = 108) and white (n = 105) women, BMI 27-30 kg/m(2). Insulin sensitivity was assessed with intravenous glucose tolerance test and minimal modeling; fat distribution with computed tomography; body composition with dual-energy X-ray absorptiometry; markers of inflammation (tumor necrosis factor (TNF)-alpha, soluble tumor necrosis factor receptor (sTNFR)-1, sTNFR-2, C-reactive protein (CRP), and interleukin (IL)-6) with enzyme-linked immunosorbent assay (ELISA). Whites had greater intra-abdominal adipose tissue (IAAT), insulin sensitivity, and concentrations of TNF-alpha, sTNFR-1, and sTNFR-2 than African Americans. Greater TNF-alpha in whites vs. African Americans was attributed to greater IAAT in whites. Among whites, but not African Americans, CRP was independently and inversely associated with insulin sensitivity, after adjusting for IAAT (r = -0.29 P < 0.05, and r = -0.13 P = 0.53, respectively). Insulin sensitivity remained lower in African Americans after adjusting for CRP (P < 0.001). In conclusion, greater IAAT among whites may be associated with greater inflammation. Insulin sensitivity was lower among African Americans, independent of obesity, fat distribution, and inflammation.

Ethnicity and weight status affect the accuracy of proxy indices of insulin sensitivity.

This study tested the hypotheses that correlations between direct measures of insulin sensitivity and proxy indices of insulin sensitivity derived from fasting values, (i) would not be affected by ethnicity, and (ii) would be stronger in overweight vs. weight-reduced states. We further hypothesized that associations between proxy indices and fat distribution would be similar to those between directly measured insulin sensitivity and fat distribution. Testing was performed in weight-stable conditions in 59 African-American (AA) and 62 white-American (WA) overweight, premenopausal women before and after a weight loss intervention. Subjects were retested 1 year following weight loss. Proxy indices were correlated against the insulin sensitivity index S(I) determined via minimal modeling. Fat distribution was assessed using computed tomography. Correlations between Si and proxy indices were consistently stronger among overweight women (r = 0.44-0.52) vs. weight-reduced women (r = 0.18-0.32), and among AA (r = 0.49-0.56, baseline; 0.24-0.36, weight-reduced) vs. WA (r = 0.38-0.46, baseline; 0.19-0.31, weight-reduced). Among subjects who regained >3 kg after 1 year, correlations between S(I) and proxy indices were similar to those observed at baseline, whereas correlations were weak among women who maintained their reduced body weight. S(I) and all proxy indices were similarly correlated with intra-abdominal adipose tissue (IAAT) at baseline, but not after weight loss. In conclusion, correlations between S(I) and proxy indices were affected by both ethnicity and weight status. If proxy indices are used in multiethnic populations, or in populations including both lean and overweight/obese subjects, data should be interpreted with caution.