Increased Cortisol Bioavailability,Abdominal Obesity,and the Metabolic Syndrome in Obese Women

Objective: This study was conducted to obtain a detailed profile of hypothalamo‐pituitary‐adrenal (HPA) axis activity and reactivity and its differential relationships with body fat distribution and total fat mass in premenopausal obese women. Research Methods and Procedures: Cortisol responses to stimulation (awakening, food intake, exercise) and suppression (0.25 mg dexamethasone), cortisol metabolism, and tissue sensitivity to glucocorticoids were studied in 53 premenopausal obese women grouped according to their waist‐to hip ratio: women with abdominal body fat distribution (A‐BFD; n = 31) and women with peripheral fat distribution (P‐BFD; n = 22). Results: Comparatively, A‐BFD women had 1) lower awakening salivary cortisol levels; 2) increased salivary responsiveness to a standardized lunch; 3) similar pituitary sensitivity to dexamethasone but decreased sensitivity of monocytes to dexamethasone; 4) similar 24‐hour urinary free cortisol but increased 24‐hour urinary ratio of cortisone‐to‐cortisol; and 5) no difference in corticosteroid binding protein parameters. Discussion: Although abdominal obesity is not very different from generalized obesity in terms of HPA function, subtle variations in HPA axis activity and reactivity are evidenced in A‐BFD premenopausal obese women.     

Impaired fat-induced thermogenesis in obese subjects: the NUGENOB study

Objectives: To study energy expenditure before and 3 hours after a high‐fat load in a large cohort of obese subjects (n = 701) and a lean reference group (n = 113). Research Methods and Procedures: Subjects from seven European countries underwent a 1‐day clinical study with a liquid test meal challenge containing 95% fat (energy content was 50% of estimated resting energy expenditure). Fasting and 3‐hour postprandial energy expenditures, as well as metabolites and hormones, were determined. Results: Obese subjects had a reduced postprandial energy expenditure after the high‐fat load, independent of body composition, age, sex, research center, and resting energy expenditure, whereas within the obese group, thermogenesis increased again with increasing BMI category. Additionally, insulin resistance, habitual physical activity, postprandial plasma triacylglycerols, and insulin were all independently positively related to the postprandial energy expenditure. Resting energy expenditure, adjusted for fat‐free mass, increased with degree of obesity, a difference that disappeared after adjustment for fat mass. Furthermore, insulin resistance, fasting plasma free fatty acids, and cortisol were positively associated, whereas fasting plasma leptin and insulin‐like growth factor‐1 were negatively associated, with resting energy expenditure. Discussion: The 3‐hour fat‐induced thermogenic response is reduced in obesity. It remains to be determined whether this blunted thermogenic response is a contributory factor or an adaptive response to the obese state.     

Seasonal Variation in Human Salivary Cortisol Concentration

Measurement of cortisol concentration can contribute important information about an individual's ability to adjust to various environmental demands of both physical and psychosocial origin. However, one uncertainty that affects the possibilities of correctly interpreting and designing field studies is the lack of observations of the impact of seasonal changes on cortisol excretion. For this reason, the month‐to‐month changes in diurnal cortisol concentration, the awakening cortisol response (ACR), maximum morning concentration, and fall during the day were studied in a group of 24 healthy men and women 32 to 61 yrs of age engaged in active work. On one workday for 12 consecutive months, participants collected saliva at four time points for determination of cortisol: at awakening, +30 min, +8 h, and at 21:00 h. Data were analyzed by a repeated measures design with month (12 levels) and time‐of‐day (4 levels) as categorical predictors. Cortisol concentrations were analyzed on a log scale. The diurnal pattern of cortisol was similar across months (interaction between month and time of day: p>0.4). The main effects of month and time‐of‐day were statistically significant (p <0.001). Highest concentrations were observed in February, March, and April, and lowest concentrations were observed in July and August. There were no statistically significant effects in any of the other measures, or between men and women. In conclusion, a seasonal variation in salivary cortisol concentrations was detected in an occupationally active population. Thus, seasonal variation needs to be taken into account when designing and evaluating field studies and interventions and when making comparisons across studies.     

Differences in daily energy expenditure in lean and obese women: the role of posture allocation

Objective: A low resting metabolic rate (RMR) is considered a risk factor for weight gain and obesity; however, due to the greater fat‐free mass (FFM) found in obesity, detecting an impairment in RMR is difficult. The purposes of this study were to determine the RMR in lean and obese women controlling for FFM and investigate activity energy expenditure (AEE) and daily activity patterns in the two groups. Methods and Procedures: Twenty healthy, non‐smoking, pre‐menopausal women (10 lean and 10 obese) participated in this 14‐day observational study on free‐living energy balance. RMR was measured by indirect calorimetry; AEE and total energy expenditure (TEE) were calculated using doubly labeled water (DLW), and activity patterns were investigated using monitors. Body composition including FFM and fat mass (FM) was measured by dual energy X‐ray absorptiometry (DXA). Results: RMR was similar in the obese vs. lean women (1601 ± 109 vs. 1505 ± 109 kcal/day, respectively, P = 0.12, adjusting for FFM and FM). Obese women sat 2.5 h more each day (12.7 ± 3.2 h vs. 10.1 ± 2.0 h, P < 0.05), stood 2 h less (2.7 ± 1.0 h vs. 4.7 ± 2.2 h, P = 0.02) and spent half as much time in activity than lean women (2.6 ± 1.5 h vs. 5.4 ± 1.9 h, P = 0.002). Discussion: RMR was not lower in the obese women; however, they were more sedentary and expended less energy in activity than the lean women. If the obese women adopted the activity patterns of the lean women, including a modification of posture allocation, an additional 300 kcal could be expended every day.     

Effects of β2‐Adrenergic Receptor Gene Variants on Adiposity: The HERITAGE Family Study

We investigated whether the Arg16Gly and Gln27Glu polymorphisms of the β2‐adrenergic receptor gene were associated with body‐fat and fat‐distribution phenotypes measured before and in response to a 20‐week endurance‐training program. BMI, fat mass (FAT), percentage of body fat (%FAT), sum of eight skinfolds (SF8), and abdominal fat areas assessed by computed tomography were measured in adult sedentary white and black participants of the HERITAGE Family Study. Evidence of gene‐by‐obesity interaction was found in whites for several adiposity phenotypes measured before training. Analyses performed separately in nonobese and obese subjects revealed that obese men carrying the Glu27 allele have lower fat accumulation (BMI, FAT, and %FAT) than noncarriers. Among white obese women, Gly16Gly homozygotes had a lower fat accumulation (BMI, FAT, and SF8) than Arg16Gly and Arg16Arg carriers. In response to endurance training, white women with the Arg16Arg genotype exhibited a greater reduction in BMI, FAT, and %FAT. Results observed in blacks were mostly negative. These results suggest that polymorphisms in the β2‐adrenergic receptor gene influence the amount of body fat in white obese men (Gln27Glu) and women (Arg16Gly), as well as the changes in adiposity in response to endurance training in white women (Arg16Gly).     

Weight loss strategies for obese adults: personalized weight management program vs. standard care

Objective: The objective of this study was to evaluate the effect of a 32‐week personalized Polar weight management program (PWMP) compared with standard care (SC) on body weight, body composition, waist circumference, and cardiorespiratory fitness in overweight or obese adults. Research Methods and Procedures: Overweight or obese (29 ± 2 kg/m²) men and women (n = 74) 38 ± 5 years of age were randomly assigned into either PWMP (men = 20, women = 21) or SC (men = 15, women = 18). Both groups managed their own diet and exercise program after receiving the same standardized nutrition and physical activity advice. PWMP also received a weight management system with literature to enable the design of a personalized diet and exercise weight loss program. Body weight and body composition, waist circumference, and cardiorespiratory fitness were measured at weeks 0, 16, and 32. Results: Eighty percent of participants completed the 32‐week intervention, with a greater proportion of the dropouts being women (PWMP: 2 men vs. 7 women; SC: 2 men vs. 4 women). At 32 weeks, PWMP completers had significantly (p < 0.001) greater losses in body weight [6.2 ± 3.4 vs. 2.6 ± 3.6 (standard deviation) kg], fat mass (5.9 ± 3.4 vs. 2.2 ± 3.6 kg), and waist circumference (4.4 ± 4.5 vs. 1.0 ± 3.6 cm). Weight loss and fat loss were explained by the exercise energy expenditure completed and not by weekly exercise duration. Discussion: More effective weight loss was achieved after treatment with the PWMP compared with SC. The results suggest that the PWMP enables effective weight loss through tools that support self‐monitoring without the requirement of more costly approaches to program supervision.     

Usefulness of Anthropometry and DXA in Predicting Intra‐abdominal Fat in Obese Men and Women

Objective: To investigate the usefulness of anthropometry and DXA in predicting intra‐abdominal fat (IAF) in obese men and women. Research Methods and Procedures: Observational, cross sectional study of 22 women and 18 men with a body mass index of 30 or above. IAF from 20 cm above and 10 cm below the L4 to L5 intervertebral disc was measured by magnetic resonance imaging (MRI) as a reference method. Central abdominal fat was measured from the upper border of L2 to the lower border of L4 by DXA. Waist and hip circumferences were also measured. Results: In obese women DXA, waist circumference and waist‐hip ratio were equally well correlated with IAF (r = 0.74, 0.75, and 0.70, respectively). In obese men DXA was moderately correlated with IAF measured by MRI (r = 0.46), whereas waist circumference and waist‐hip ratio were not significantly correlated with IAF. Discussion: The prediction of IAF in obese subjects was highly dependent on sex more than in non‐obese persons. Anthropometry and DXA were equally useful in obese women, whereas anthropometry had no predictive power and DXA was the only acceptable predictor of IAF in obese men.     

The effect of pioglitazone and resistance training on body composition in older men and women undergoing hypocaloric weight loss

Age‐related increases in ectopic fat accumulation are associated with greater risk for metabolic and cardiovascular diseases, and physical disability. Reducing skeletal muscle fat and preserving lean tissue are associated with improved physical function in older adults. PPARγ‐agonist treatment decreases abdominal visceral adipose tissue (VAT) and resistance training preserves lean tissue, but their effect on ectopic fat depots in nondiabetic overweight adults is unclear. We examined the influence of pioglitazone and resistance training on body composition in older (65–79 years) nondiabetic overweight/obese men (n = 48, BMI = 32.3 ± 3.8 kg/m²) and women (n = 40, BMI = 33.3 ± 4.9 kg/m²) during weight loss. All participants underwent a 16‐week hypocaloric weight‐loss program and were randomized to receive pioglitazone (30 mg/day) or no pioglitazone with or without resistance training, following a 2 × 2 factorial design. Regional body composition was measured at baseline and follow‐up using computed tomography (CT). Lean mass was measured using dual X‐ray absorptiometry. Men lost 6.6% and women lost 6.5% of initial body mass. The percent of fat loss varied across individual compartments. Men who were given pioglitazone lost more visceral abdominal fat than men who were not given pioglitazone (?1,160 vs. ?647 cm³, P = 0.007). Women who were given pioglitazone lost less thigh subcutaneous fat (?104 vs. ?298 cm³, P = 0.002). Pioglitazone did not affect any other outcomes. Resistance training diminished thigh muscle loss in men and women (resistance training vs. no resistance training men: ?43 vs. ?88 cm³, P = 0.005; women: ?34 vs. ?59 cm³, P = 0.04). In overweight/obese older men undergoing weight loss, pioglitazone increased visceral fat loss and resistance training reduced skeletal muscle loss. Additional studies are needed to clarify the observed gender differences and evaluate how these changes in body composition influence functional status.     

Postprandial Cytokine Concentrations and Meal Composition in Obese and Lean Women

The aim of this study was to compare the acute effect of (i) meals rich in saturated fat, oleic acid, and α‐linolenic acid and (ii) meals rich in starch and fiber on markers of inflammation and oxidative stress in obese and lean women. In a crossover study, 15 abdominally obese women (age, 54 ± 9 years; BMI, 37.3 ± 5.5 kg/m2) and 14 lean women (age, 53 ± 10 years; BMI, 22.9 ± 1.9 kg/m2) consumed meals rich in cream (CR), olive oil (OL), canola oil (CAN), potato (POT), and All‐Bran (BRAN) in random order. Blood samples were collected before and up to 6 h after the meals and plasma interleukin‐6 (IL‐6), IL‐8, tumor necrosis factor‐α (TNF‐α), lipid peroxides (LPOs), free‐fatty acids (FFAs), insulin, glucose, and cortisol were measured. Plasma IL‐6 decreased significantly 1 h after the meals then increased significantly above baseline at 4 h and 6 h in obese women and at 6 h in lean women. The incremental area under the curve (iAUC) for IL‐6 was significantly (P = 0.02) higher in obese compared with lean women and was significantly lower following the high fiber BRAN meal compared with a POT meal (P = 0.003). Waist circumference (R = 0.491, P = 0.007) and cortisol AUC (R = ?0.415, P = 0.03) were significant determinants of the magnitude of 6 h changes in plasma IL‐6 after the meals. These findings suggest that the postprandial response of plasma IL‐6 concentrations may be influenced by the type of carbohydrate in the meal, central adiposity, and circulating cortisol concentrations in women.     

Sex-specific difference in the interconversion of cortisol and cortisone in men and women

Objective: Our objective was to demonstrate that the smaller oxoreductase activity of 11β‐HSD1 in women would shift the interconversion of cortisol and cortisone toward cortisone, resulting in a larger amount of generated labeled cortisone in healthy women than in healthy men. Research Methods and Procedures: Using mass spectrometry, the amount of cortisone generated from a continuous infusion (8 am to 6 pm ) of stable‐labeled cortisol (1α,2α‐d‐cortisol) was determined in non‐obese and in obese (BMI >35 kg/m²) men and women during steady‐state conditions (from 2 pm to 6 pm ). In this setting, the amount of generated labeled cortisone (expressed as % of the achieved steady‐state concentrations of labeled cortisol) reflects the sum of the bi‐directional conversion of cortisol into cortisone (and vice versa) by 11β‐hydroxysteroid dehydrogenase. Results: The amount of generated labeled cortisone was higher in men than in women (p < 0.0001). This sex difference was higher in obese than in non‐obese patients (p = 0.0062). Conclusions: The interconversion of cortisol and cortisone during steady‐state conditions is shifted toward cortisol in men as compared with women. This suggests a higher overall oxoreductase activity of 11β‐hydroxysteroid dehydrogenase type 1 in men than in women. This sex‐specific difference is maintained in obesity.     

Regional body volumes, BMI, waist circumference, and percentage fat in severely obese adults

Objective: This study presents total body volume (TBV) and regional body volume, and their relationships with widely used body composition indices [BMI, waist circumference (WC), and percentage body fat (% fat)] in severely obese adults (BMI ≥35 kg/m²). Research Methods and Procedures: We measured TBV, trunk volume (TV), arm volume (AV), leg volume (LV), and WC and estimated % fat in 32 severely obese persons with BMI 36 to 62 kg/m² (23 women; age, 19 to 65 years; weight, 91 to 182 kg) and in 58 persons with BMI <35 kg/m² (28 women; age, 18 to 83 years; weight, 48 to 102 kg) using a newly validated 3‐day photonic image scanner (3DPS, Model C9036–02, Hamamatsu Co., Japan) and calculated TV/TBV, AV/TBV, and LV/TBV. Results: Men had significantly larger TBV and higher TV/TBV and AV/TBV, but significantly lower LV/TBV than women, independently of BMI. TV/TBV increased while AV/TBV and LV/TBV decreased with increasing BMI, WC, and % fat, and the rate of increase in TV/TBV per % fat was significantly greater in severely obese individuals than in individuals with BMI <35 kg/m². The relationships for TBV with % fat were much lower than with BMI or WC. Conclusion: Body volume gains were mainly in the trunk region in adults, irrespective of sex or BMI. For a given BMI, WC, or % fat, men had a significantly larger TV than women. The implication is that men could have higher health risks due to having higher trunk body weight as a proportion of total body weight compared with severely obese or less severely obese women.     

Ghrelin Does Not Influence Gastric Emptying in Obese Subjects

Objective: To evaluate the relationship between fasting plasma concentrations of ghrelin and gastric emptying in obese individuals compared with lean subjects. Research Methods and Procedures: We included 20 obese patients (9 men and 11 women, BMI > 30 kg/m²) and 16 nonobese control subjects (7 men and 9 women, BMI ≤ 25 kg/m²). Gastric emptying of solids (egg sandwich labeled with radionuclide) was measured at 120 minutes with (99m)Tc‐single photon emission computed tomography imaging. Ghrelin and leptin were analyzed by radioimmunoassay and ELISA methods, respectively. Results: The gastric half‐emptying time was similar in obese men and women (67.8 ± 14.79 vs. 66.6 ± 13.56 minutes) but significantly shorter (p < 0.001) than in the control population (men: 88.09 ± 11.72 minutes; women: 97.25 ± 10.31 minutes). Ghrelin levels were significantly lower in obese subjects (131.37 ± 47.67 vs. 306.3 ± 45.52 pg/mL; p < 0.0001 in men and 162.13 ± 32.95 vs. 272.8 ± 47.77 pg/mL; p < 0.0001 in women). A negative correlation between gastric emptying and fasting ghrelin levels was observed only in lean subjects (y = ?0.2391x + 157.9; R² = 0.95). Also, in the lean group, ghrelin was the only significant independent determinant of gastric emptying, explaining 98% of the variance (adjusted R²) in a multiple regression analysis. Discussion: This report shows that, in humans, gastric emptying is faster in obese subjects than in lean controls and that, whereas ghrelin is the best determinant of gastric kinetics in healthy controls, this action is lost in obesity.     

Very low-carbohydrate versus isocaloric high-carbohydrate diet in dietary obese rats

Objective: The effects of a very low‐carbohydrate (VLC), high‐fat (HF) dietary regimen on metabolic syndrome were compared with those of an isocaloric high‐carbohydrate (HC), low‐fat (LF) regimen in dietary obese rats. Research Methods and Procedures: Male Sprague‐Dawley rats, made obese by 8 weeks ad libitum consumption of an HF diet, developed features of the metabolic syndrome vs. lean control (C) rats, including greater visceral, subcutaneous, and hepatic fat masses, elevated plasma cholesterol levels, impaired glucose tolerance, and fasting and post‐load insulin resistance. Half of the obese rats (VLC) were then fed a popular VLC‐HF diet (Weeks 9 and 10 at 5% and Weeks 11 to 14 at 15% carbohydrate), and one‐half (HC) were pair‐fed an HC‐LF diet (Weeks 9 to 14 at 60% carbohydrate). Results: Energy intakes of pair‐fed VLC and HC rats were less than C rats throughout Weeks 9 to 14. Compared with HC rats, VLC rats exhibited impaired insulin and glycemic responses to an intraperitoneal glucose load at Week 10 and lower plasma triacylglycerol levels but retarded loss of hepatic, retroperitoneal, and total body fat at Week 14. VLC, HC, and C rats no longer differed in body weight, plasma cholesterol, glucose tolerance, or fasting insulin resistance at Week 14. Progressive decreases in fasting insulin resistance in obese groups paralleled concomitant reductions in hepatic, retroperitoneal, and total body fat. Discussion: When energy intake was matched, the VLC‐HF diet provided no advantage in weight loss or in improving those components of the metabolic syndrome induced by dietary obesity and may delay loss of hepatic and visceral fat as compared with an HC‐LF diet.     

Differences in Resting Metabolic Rate between White and African‐American Young Adults

Objective: A reported lower resting metabolic rate (RMR) in African‐American women than in white women could explain the higher prevalence of obesity in the former group. Little information is available on RMR in African‐American men. Research Methods and Procedures: We assessed RMR by indirect calorimetry and body composition by DXA in 395 adults ages 28 to 40 years (100 African‐American men, 95 white men, 94 African‐American women, and 106 white women), recruited from participants in the Coronary Artery Risk Development in Young Adults (CARDIA), Birmingham, Alabama, and Oakland, California, field centers. Results: Using linear models, fat‐free mass, fat mass, visceral fat, and age were significantly related to RMR, but the usual level of physical activity was not. After adjustment for these variables, mean RMR was significantly higher in whites (1665.07 ± 10.78 kcal/d) than in African Americans (1585.05 ± 11.02 kcal/d) by 80 ± 16 kcal/d (p < 0.0001). The ethnic × gender interaction was not significant (p = 0.9512), indicating that the difference in RMR between African‐American and white subjects was similar for men and women. Discussion: RMR is ～5% higher in white than in African‐American participants in CARDIA. The difference was the same for men and women and for lean and obese individuals. The prevalence of obesity is not higher in African‐American men than in white men. Because of these reasons, we believe that RMR differences are unlikely to be a primary explanation for why African‐American women are more prone to obesity than white women.     

Evaluation of a multisensor armband in estimating energy expenditure in obese individuals

Objective: To examine the reliability and validity of the SenseWear Pro 2 Armband (SWA; Body Media, Pittsburgh, PA) during rest and exercise compared with indirect calorimetry (IC) in obese individuals. Research Methods and Procedures: Energy expenditure was assessed during rest with the SWA and IC in 142 obese adults (37 men and 105 women, BMI = 42.3 ± 7.0) and in 25 lean and overweight adults (BMI = 25.3 ± 3.2) who were used as a comparison group. Twenty‐nine of the obese adults also participated in three separate short exercise sessions including cycle ergometry, stair stepping, and treadmill walking. Results: The repeatability of SWA estimates in obese subjects was high (r = 0.88, p < 0.001). The SWA generally underestimated the resting energy expenditure (REE) (1811 ± 346 vs. 1880 ± 382 kcal/d) and highly overestimated the energy expenditure during the exercise sessions in obese individuals. REE estimations by SWA were significantly correlated with fat‐free mass (r = 0.88, p < 0.001). Bland‐Altman plots based statistical analysis for the estimated REE, and measured IC showed a low agreement (Total Error > 20% but Systematic Error < 5%) between the two methods in obese subjects, although they showed a high correlation and a very good agreement in lean and overweight patients. Discussion: The SWA is an easy to handle, practical, new portable device for measuring energy expenditure. The accuracy of the SWA appeared to be poor in the obese subjects we examined, especially those with high REE both in rest and exercise. We believe that it is necessary to incorporate new, obesity‐specific algorithms in the relative software.     

Development of a real‐time PCR method for Firmicutes and Bacteroidetes in faeces and its application to quantify intestinal population of obese and lean pigs

Aims: To investigate whether the relative abundance of the Bacteroidetes and Firmicutes divisions in pigs is different between obese and lean animals. Methods and Results: Group‐specific primers were designed to target the 16S rRNA genes of Bacteroidetes and Firmicutes present in the gut. After the validation of their specificity, these primers were used in the real‐time PCR quantification of all Bacteria, Firmicutes division, Bacteroidetes division and Bacteroides spp. in the faecal samples of obese and lean pigs from Banna mini‐pig inbred line. The obese pigs had a ～61% fewer percentage (based on all Bacteria) of Bacteroidetes division (P = 0·033) and a ～56% fewer proportion of Bacteroides spp. (P = 0·047) than the lean pigs. The proportions of both Bacteroidetes and Bacteroides had a negative correlation (P < 0·01) with the body weight. Conclusion: The results suggested that the fat storage might affect the proportion of Bacteroidetes division in the gut. Significance and Impact of the Study: The real‐time PCR assays developed for Firmicutes and Bacteroidetes will be useful for investigating the composition of gut microbiota.     

Body composition and fatness patterns in Prader-Willi syndrome: comparison with simple obesity

Objective: To characterize the body composition of Prader‐Willi syndrome (PWS) subjects and compare with simple obesity. Research Methods and Procedures: Seventy‐two individuals (27 PWS deletion, 21 PWS uniparental disomy, and 24 obese controls) 10 to 49 years old were studied with the use of DXA. Body composition measures were obtained, and regional fat and lean mass patterns were characterized. Significant differences were assessed with Student's t test and ANOVA adjusting for age, gender, and BMI. Results: Significant differences between the PWS and obese groups were found for lean measures of the arms, legs, and trunk. Total lean mass was significantly lower in PWS than in obese subjects for arms, trunk, and especially legs. Furthermore, two body regions (legs and trunk) showed significant differences for fat and lean measures between PWS and obese males. However, significant differences between PWS and obese females for these measures were found only for the legs. No significant differences were identified between PWS deletion and uniparental disomy subjects. Discussion: Our results demonstrate that PWS individuals do, in fact, have an unusual body composition and fatness patterns, characterized by reduced lean tissue and increased adiposity, with PWS males contributing most with fat patterns more similar to females.     

Enhanced circadian ACTH release in obese premenopausal women: reversal by short-term acipimox treatment

Several studies suggest that the hypothalamo-pituitary-adrenal (HPA) axis is exceedingly active in obese individuals. Experimental studies show that circulating free fatty acids (FFAs) promote the secretory activity of the HPA axis and that human obesity is associated with high circulating FFAs. We hypothesized that HPA axis activity is enhanced and that lowering of circulating FFAs by acipimox would reduce spontaneous secretion of the HPA hormonal ensemble in obese humans. To evaluate these hypotheses, diurnal ACTH and cortisol secretion was studied in 11 obese and 9 lean premenopausal women (body mass index: obese 33.5 +/- 0.9 vs. lean 21.2 +/- 0.6 kg/m(2), P < 0.001) in the early follicular stage of their menstrual cycle. Obese women were randomly assigned to treatment with either acipimox (inhibitor of lipolysis, 250 mg orally four times daily) or placebo in a double-blind crossover design, starting one day before admission until the end of the blood-sampling period. Blood samples were taken during 24 h with a sampling interval of 10 min for assessment of plasma ACTH and cortisol concentrations. ACTH and cortisol secretion rates were estimated by multiparameter deconvolution analysis. Daily ACTH secretion was substantially higher in obese than in lean women (7,950 +/- 1,212 vs. 2,808 +/- 329 ng/24 h, P = 0.002), whereas cortisol was not altered (obese 36,362 +/- 5,639 vs. lean 37,187 +/- 4,239 nmol/24 h, P = 0.912). Acipimox significantly reduced ACTH secretion in the obese subjects (acipimox 5,850 +/- 769 ng/24 h, P = 0.039 vs. placebo), whereas cortisol release did not change (acipimox 33,542 +/- 3,436 nmol/24 h, P = 0.484 vs. placebo). In conclusion, spontaneous ACTH secretion is enhanced in obese premenopausal women, whereas cortisol production is normal. Reduction of circulating FFA concentrations by acipimox blunts ACTH release in obese women, which suggests that FFAs are involved in the pathophysiology of this neuroendocrine anomaly.     

Adiponectin Levels during Low‐ and High‐Fat Eucaloric Diets in Lean and Obese Women

Objective: Adiponectin influences insulin sensitivity (S_I) and fat oxidation. Little is known about changes in adiponectin with changes in the fat content of eucaloric diets. We hypothesized that dietary fat content may influence adiponectin according to an individual's S_I. Research Methods and Procedures: We measured changes in adiponectin, insulin, glucose, and leptin in response to high‐fat (HF) and low‐fat (LF) eucaloric diets in lean (n = 10) and obese (n = 11) subjects. Obese subjects were further subdivided in relation to a priori S_I. Results: We found significantly higher insulin, glucose, and leptin and lower adiponectin in obese vs. lean subjects during both HF and LF. The mean group values of these measurements, including adiponectin (lean, HF 21.9 ± 9.8; LF, 20.8 ± 6.6; obese, HF 10.0 ± 3.3; LF, 9.5 ± 2.3 ng/mL; mean ± SD), did not significantly change between HF and LF diets. However, within the obese group, the insulin‐sensitive subjects had significantly higher adiponectin during HF than did the insulin‐resistant subjects. Additionally, the change in adiponectin from LF to HF diet correlated positively with the obese subjects’ baseline S_I. Discussion: Although in lean and obese women, group mean values for adiponectin did not change significantly with a change in fat content of a eucaloric diet, a priori measured S_I in obese subjects predicted an increase in adiponectin during the HF diet; this may be a mechanism that preserves S_I in an already obese group.