Body mass index to predict fat mass and metabolic syndrome severity: should it really be specific to sex, age and ethnicity? A NHANES study (1999-2014).

Background: Body mass index (BMI) is often criticised since it doesn't consider sex, age and ethnicity, which may affect the height scaling exponent of the equation.Aims: First, to identify specific height scaling exponents (α) based on sex, age and ethnicity. Second, to assess the performance of the current vs the proposed BMI equations (1) to predict total fat mass (TFM) and metabolic syndrome (MetS) severity and (2) to correctly identify obese individuals and those having MetS.Methods: In total, 41,403 individuals aged 20-80 years (NHANES, 1999-2014) were studied. Specific "α" were identified using the Benn formula. Various statistical approaches were performed to assess performances of the current vs the proposed-BMIs.Results: The proposed "α" varies from 1.2 to 2.5, after considering sex, age and ethnicity. BMIs calculated using the proposed "α" showed a similar capacity to predict TFM and MetS severity and to correctly identify obese individuals and those having MetS compared to the current BMI.Conclusions: Despite sex, age and ethnicity modulating the height scaling exponent of the BMI equation, using these proposed exponents in the BMI equation didn't improve the capacity to predict TFM and MetS severity, suggesting that the current BMI remains a valid clinical tool.

Vasomotor symptoms and cardiometabolic risk factors in menopausal women: a MONET Group study.

INTRODUCTION: Conflicting results have been reported concerning the prevalence of cardiometabolic risk factors in women experiencing vasomotor symptoms (VMS). OBJECTIVES: To compare cardiometabolic risk factors between women with and without VMS during the menopause transition and to determine the influence of physical activity on the prevalence of VMS. METHODS: Yearly assessment of women transitioning through menopause included self-reported VMS (hot flushes and night sweats), body composition and fat distribution, fasting glucose, insulin and lipids, and physical activity levels. RESULTS: Eighty-five of the 102 premenopausal women at baseline were included (age: 49.9 ± 2.0 years; body mass index: 23.2 ± 2.2 kg/m(2)). According to linear mixed model analyses, no statistically significant differences were observed for fat mass, lean body mass, body fat distribution indices and cardiometabolic risk factors, when comparing symptomatic vs. asymptomatic women. Neither physical activity levels nor intensity were associated with the prevalence of VMS. CONCLUSION: Our results suggest that women transitioning through menopause who reported VMS did not show greater deteriorations in body composition, body fat distribution and cardiometabolic risk factors. Furthermore, physical activity levels were not associated with lower prevalence of vasomotor symptoms in the present cohort.

Satiety quotient linked to food intake and changes in anthropometry during menopause: a MONET Study.

OBJECTIVES: It is unknown whether the satiety quotient (SQ) differs across the menopausal transition, and whether changes in SQ are related to changes in anthropometric/body composition variables. The objective of this study was to evaluate the changes in SQ and its association with energy intake and changes in anthropometric/body composition variables across the menopausal transition. METHODS: At baseline, 102 premenopausal women (aged 49.9 ± 1.9 years, body mass index 23.3 ± 2.2 kg/m(2)) took part in a 5-year observational, longitudinal study. Body composition (DXA), appetite (visual analog scales), energy and macronutrient intakes (ad libitum lunch and 7-day food diary) were assessed annually. The SQ (mm/100 kcal) was calculated at 60 and 180 min post-breakfast consumption. RESULTS: Overall, the SQ increased at years 3 and 4 (p = 0.01-0.0001), despite no significant differences between menopausal status groups. Lower fullness, prospective food consumption and mean SQ values predicted overall increases in lunch energy and macronutrient intakes (p = 0.04-0.01), whereas only prospective food consumption and fullness SQ predicted energy intake and carbohydrate intake, respectively, when assessed with food diaries (p = 0.01). Delta SQs were negatively correlated with changes in waist circumference (p = 0.03-0.02), whereas delta SQs were positively (p = 0.04) and negatively (p = 0.02) associated with delta fat mass between years 1 and 5, and years 4 and 5, respectively. CONCLUSION: These results suggest that variations in SQ across the menopausal transition are related to energy and macronutrient intakes and coincide with changes in body composition and waist circumference.

Light physical activity is a better determinant of lower adiposity during the menopausal transition.

OBJECTIVE: To investigate the relationship between time spent performing physical activity (PA) and adiposity across the menopausal transition. METHODS: Body weight and body composition were analyzed in 65 women (47-54 years old; body mass index 23.2 ± 2.4 kg/m(2)) in a 5-year prospective study. Time spent in PA of varying intensities (sedentary, light, moderate and vigorous) was determined from 7-day accelerometer measurement and energy intake with a 7-day food diary. RESULTS: Significant negative correlations were observed between the time spent in light-intensity PA and fat mass (FM) (r = -0.38, p < 0.005), central FM (r = -0.36, p < 0.005), peripheral FM (r = -0.33, p < 0.01), and percent body fat (r = -0.42, p < 0.001) at year 1, respectively. No significant correlations were noted between measures of adiposity and time spent performing either moderate or vigorous PA. Analyses using tertiles of time spent in light PA at year 1 showed that FM (20.7 ± 4.0 vs. 20.3 ± 6.6 vs. 16.6 ± 4.6 kg, p < 0.05), central FM (10.1 ± 2.6 vs. 10.0 ± 3.8 vs. 7.8 ± 2.4 kg; p < 0.05) and percent body fat (34.5 ± 5.1 vs. 32.2 ± 7.7 vs. 28.1 ± 6.2%, p < 0.01) were all significantly lower in women in the highest tertile. These differences remained significant after covariate analyses using time spent in moderate- and high-intensity PA and total energy intake. Finally, lower levels of FM, percent body fat, central and peripheral FM persisted in women who spent more time in light PA (highest tertiles) over the 5-year follow-up. CONCLUSION: Our results suggest that the time spent performing light PA may have a greater impact on adiposity than moderate and/or vigorous PA, an observation independent of the menopausal status.

Soy isoflavones and exercise to improve physical capacity in postmenopausal women.

AIM: In postmenopause, ovarian decline along with sedentary lifestyle could contribute to the loss of lean body mass (LBM) and muscle strength. This study aimed to verify whether exercise and isoflavones could have additive effects on muscle quality, muscle mass index, relative strength and physical capacity in overweight sedentary postmenopausal women. METHOD: We recruited 70 overweight-to-obese (body mass index 32.2±4.8 kg/m(2)) postmenopausal women (59±5 years old) to participate in a 6-month clinical study combining isoflavones (70 mg/day) and exercise (resistance and aerobic training) treatments. Subjects were divided into four groups: (1) placebo (n =15), (2) isoflavones (n =15), (3) exercise and placebo (n =20), and (4) exercise and isoflavone (n =20). Principal outcome variables included maximal muscle strength (1RM) at the leg press and the bench press, muscle mass index, muscle quality in the legs and relative strength. RESULTS: After 6 months of training, exercise produced 49% and 23% increases, respectively, in leg press and bench press 1RM (p ≤0.01). Leg relative strength and muscle quality increased by more than 50% (both p <0.01), while muscle mass index increased by 7% (p <0.05) in both exercise groups only. CONCLUSION: Exercise training can improve muscle tissue strength, function and quality in sedentary postmenopausal women. Isoflavones, irrespective of exercise, did not produce changes in these variables. From a clinical perspective, these results suggest that overweight women could reduce the risks of mobility impairments, even in the absence of weight loss, by following a sound exercise intervention that includes both resistance and aerobic training at a high intensity.

Mineralocorticoids participate in the reduced vascular reactivity of pregnant rats.

The renin-angiotensin-aldosterone (RAA) system is markedly activated in pregnancy. We evaluated if mineralocorticoid receptors (MR), a major component of the RAA system, are involved in the reduced vascular reactivity associated with pregnancy. Canrenoate (MR antagonist; 20 mg·kg(-1)·day(-1)) was administered to nonpregnant (NP) rats for 7 days and to pregnant rats from day 15 to 22 of gestation. These were killed on day 17, 19, or 22 of gestation and, for NP rats, after 7 days treatment. Constrictor responses to phenylephrine (PhE) and KCl were measured in endothelium-denuded thoracic aortic rings under the influence of modulators of potassium (activators) and calcium (blocker) channels. Responses to the constrictors were blunted from days 17 to 22 of gestation. Although canrenoate increased responses to PhE and KCl, it did not reverse their blunted responses in gestation. NS-1619 and cromakalim (respectively, high-conductance calcium-activated potassium channels and ATP-sensitive potassium channel activators) diminished responses to both PhE and KCl. Inhibition by NS-1619 on responses to both agonists was decreased under canrenoate treatment in NP, but the reduced influence of NS-1619 during gestation was reversed by the mineralocorticoid antagonist. Cromakalim reduced the response to PhE significantly in the pregnant groups; this effect was enhanced by canrenoate. Finally, nifedipine (calcium channel blocker) markedly reduced KCl responses but to a lesser extent at the end of pregnancy, an inhibiting effect that was increased with canrenoate treatment. These data demonstrate that treating rats with a MR antagonist increased vascular reactivity but that it differentially affected potassium and calcium channel activity in aortas of NP and pregnant animals. This suggests that aldosterone is one of the components involved in vascular adaptations to pregnancy.

Characterizing the profile of obese patients who are metabolically healthy.

The presence of obesity-related metabolic disturbances varies widely among obese individuals. Accordingly, a unique subset of obese individuals has been described in the medical literature, which seems to be protected or more resistant to the development of metabolic abnormalities associated with obesity. These individuals, now known as 'metabolically healthy but obese' (MHO), despite having excessive body fatness, display a favorable metabolic profile characterized by high levels of insulin sensitivity, no hypertension as well as a favorable lipid, inflammation, hormonal, liver enzyme and immune profile. However, recent studies have indicated that this healthier metabolic profile may not translate into a lower risk for mortality. Mechanisms that could explain the favorable metabolic profile of MHO individuals are poorly understood. However, preliminary evidence suggests that differences in visceral fat accumulation, birth weight, adipose cell size and gene expression-encoding markers of adipose cell differentiation may favor the development of the MHO phenotype. Despite the uncertainty regarding the exact degree of protection related to the MHO status, identification of underlying factors and mechanisms associated with this phenotype will eventually be invaluable in helping us understand factors that predispose, delay or protect obese individuals from metabolic disturbances. Collectively, a greater understanding of the MHO individual has important implications for therapeutic decision making, the characterization of subjects in research protocols and medical education.

Low-volume walking HIIT: Efficient strategy to improve physical capacity and reduce the risk of cardiovascular disease in older women with type 2 diabetes.

BACKGROUND AND AIMS: To compare the effect of a low-volume walking high-intensity interval training (HIIT) to moderate-intensity continuous training (MICT) on risk of cardiovascular diseases and physical capacity in older women with type 2 diabetes (T2D). METHODS: Thirty inactive older women with T2D were randomized into either HIIT (75 min/week) or MICT (150 min/week). Cardiovascular risk profile (lipid profile; waist circumference and fat mass; resting, post-exercise and ambulatory blood pressure [BP]; VO2 peak; UKPDS score; ABC's) and physical capacity were assessed before and after a 12-week intervention. RESULTS: While resting systolic and diastolic BP (all p ≤ 0.01) were reduced, ambulatory BP (p ≥ 0.49) and lipid profile (p ≥ 0.40) remained unchanged after the intervention. Although VO2 peak increased to a similar extent in both groups (p = 0.015), the distance covered during the 6MWT (p = 0.01) and grip strength (p = 0.02) increased to a greater extend in HIIT. The UKPDS risk score decreased in both groups after the intervention (p = 0.03) and 31% of the participants reached the ABC's compared to 24% at baseline. CONCLUSION: Low-volume walking HIIT is an efficient exercise intervention for older women with T2D as it improved some CVD risk factors and physical capacity. Nevertheless, neither low-volume HIIT nor MICT is sufficient to affect ambulatory blood pressure in T2D patients.

Relationship between the percentage of predicted cardiorespiratory fitness and cardiovascular disease risk factors in premenopausal women: a MONET study.

OBJECTIVE: To determine the relationships between the percentage predicted cardiorespiratory fitness (%CRF) and the anthropometric and metabolic cardiovascular disease risk factors in asymptomatic, premenopausal women. METHODS: Data are baseline values obtained in 97 healthy premenopausal women (age 49.9 +/- 1.9 years; body mass index 23.2 +/- 2.2 kg/m(2)) participating in a longitudinal study from 2004 to 2009. The outcome measures were peak oxygen consumption (VO(2) peak), body mass index, body composition (percentage fat, fat mass, fat-free mass), waist circumference, abdominal subcutaneous fat, visceral fat, resting blood pressure and fasting lipids, glucose and insulin levels. RESULTS: The %CRF was negatively associated with body mass index, fat mass, percentage fat, waist circumference, abdominal subcutaneous fat, visceral fat, triglycerides, triglyceride/high density lipoprotein cholesterol, total cholesterol, total cholesterol/high density lipoprotein cholesterol, fasting insulin levels and HOMA-IR (- 0.59 < or = r < or = - 0.20; 0.01 < p < 0.05) and positively associated with insulin sensitivity index (r = 0.23; p < 0.05). VO(2) peak was associated with the same variables; however, correlations were slightly better (- 0.70 < or = r < or = 0.30; 0.01 < p < 0.05). Stepwise multiple regression analysis showed that %CRF was only independently correlated with plasma triglyceride levels. CONCLUSION: The results of this study suggest that %CRF was not a major predictor of anthropometric and metabolic variables associated with an increased risk of cardiovascular disease in asymptomatic premenopausal women. Finally, the VO(2) peak is a better predictor than the %CRF to assess the risk of cardiovascular disease in asymptomatic premenopausal women.

Causal role of group B Streptococcus-induced acute chorioamnionitis in intrauterine growth retardation and cerebral palsy-like impairments.

Chorioamnionitis and intrauterine growth retardation (IUGR) are risk factors for cerebral palsy (CP). Common bacteria isolated in chorioamnionitis include group B Streptococcus (GBS) serotypes Ia and III. Little is known about the impact of placental inflammation induced by different bacteria, including different GBS strains. We aimed to test the impact of chorioamnionitis induced by two common GBS serotypes (GBSIa and GBSIII) on growth and neuromotor outcomes in the progeny. Dams were exposed at the end of gestation to either saline, inactivated GBSIa or GBSIII. Inactivated GBS bacteria invaded placentas and triggered a chorioamnionitis featured by massive polymorphonuclear cell infiltrations. Offspring exposed to GBSIII - but not to GBSIa - developed IUGR, persisting beyond adolescent age. Male rats in utero exposed to GBSIII traveled a lower distance in the Open Field test, which was correlating with their level of IUGR. GBSIII-exposed rats presented decreased startle responses to acoustic stimuli beyond adolescent age. GBS-exposed rats displayed a dysmyelinated white matter in the corpus callosum adjacent to thinner primary motor cortices. A decreased density of microglial cells was detected in the mature corpus callosum of GBSIII-exposed males - but not females - which was correlating positively with the primary motor cortex thickness. Altogether, our results demonstrate a causal link between pathogen-induced acute chorioamnionitis and (1) IUGR, (2) serotype- and sex-specific neuromotor impairments and (3) abnormal development of primary motor cortices, dysmyelinated white matter and decreased density of microglial cells.

Contribution of cellulosic fibre filter on atmosphere moisture content in laser powder bed fusion additive manufacturing.

Cellulosic materials are commonly used to manufacture the particulate filters used in laser powder bed fusion (LPBF) additive manufacturing (AM) equipment. An experimental approach has been used to calculate the moisture quantity and kinetics of sorption in a cellulosic filter at varying relative humidity (RH) levels. A prediction of the amount of moisture which can be theoretically held within a filter during storage before its use has been obtained. Subsequently, the quantity and the rate of moisture desorption which can be transferred into the build chamber during LPBF is presented. This work highlights the importance of filter storage and conditioning prior to use in additive manufacturing processing.

Body fat distribution modulates insulin sensitivity in post-menopausal overweight and obese women: a MONET study.

OBJECTIVE: Central fat mass (CFM) correlates with insulin resistance and increases the risk of type 2 diabetes and cardiovascular complications. On the other hand, increased peripheral fat mass (PFM) is associated with higher insulin sensitivity. Thus, we examined the contribution of adipose tissue distribution, as assessed by the PFM/CFM ratio, to insulin sensitivity in overweight and obese postmenopausal women. DESIGN AND METHODS: A total of 124 nondiabetic overweight and obese postmenopausal women underwent an oral glucose tolerance test (OGTT) and a hyperinsulinemic/euglycemic (HI) clamp. Body composition was determined using computed tomography for visceral adipose tissue (VAT) and dual X-ray absorptiometry for fat mass, lean body mass and their respective proportions. Participants were divided by tertiles of the PFM/CFM ratio. RESULTS: Participants with preferential CFM (group 1) had higher fasting insulin levels and insulin area under the curve (AUC) during OGTT, as well as lower glucose infusion rates during the HI clamp, whether it was expressed per kg of body weight (M) or per kg of fat-free mass (Mm), compared with the other two groups. The PFM/CFM ratio also correlated significantly with fasting insulin (r=-0.32, P<0.001), the insulin AUC (r=-0.42 P<0.001), M (r=0.39 P<0.001) and Mm (r=0.37 P<0.001). Using hierarchical regression, we demonstrated that the PFM/CFM ratio was an independent predictor of insulin AUC, M and Mm and that its sequential addition to CFM and VAT improved significantly the predictive value of the model for insulin sensitivity for all variables except fasting insulin. CONCLUSION: The PFM/CFM ratio, which integrates the antagonistic effects of both central and peripheral depots on insulin sensitivity, added substantially to the prediction of insulin sensitivity over VAT and CFM alone.

Placental oxidative stress in a rat model of preeclampsia.

The onset of preeclampsia is associated with increased maternal insult that could affect placental function. By increasing sodium intake (0.9% or 1.8% NaCl in drinking water) during the last week of gestation in the rat, we developed an animal model that shows many characteristics of preeclampsia such as increased blood pressure, decreased circulatory volume and diminished activity of the renin-angiotensin-aldosterone system. The aim of the present study was to determine in this model whether maternal perturbations in pregnancy lead to placental oxidative stress. Sprague-Dawley pregnant rats receiving salted-water were compared to not-supplemented pregnant rats. Markers of oxidative stress, ensuing cell death, and changes in the production of vasoactive substances (prostanoids: thromboxane, TxB(2); and prostacyclin, PGF(1alpha)) and the pro-inflammatory cytokine tumour necrosis factor-alpha (TNF-alpha) were measured in the placenta. In tissue from pregnant rats on 1.8% NaCl supplement, 8-iso-PGF(2alpha) levels, TxB(2)/6-keto-PGF(1alpha) ratios, total TNF-alpha RNA expression, as well as the apoptotic index (Bax/Bcl-2 ratio) and endothelial nitric oxide synthase protein expression increase while total glutathione content decreases. These findings demonstrate that maternal insult during gestation induced an imbalance in the oxidative environment in the placenta favouring oxidation. This was accompanied by an increased synthesis of vasoconstrictive substances and TNF-alpha by the placenta as well as the increased rate of placental cell apoptosis.

Effect of a High-Protein Energy-Restricted Diet Combined with Resistance Training on Metabolic Profile in Older Individuals with Metabolic Impairments.

Adequate protein intake and resistance training are effective strategies to maintain muscle mass, but the effect of their combination on metabolic profile during weight loss remains to be determined in older adults. The main objective of this study was to determine the effect of a 16-week high-protein caloric restriction combined with resistance training on chronic disease risk factors in obese older individuals with metabolic impairments. A total of 26 overweight adults aged between 60 and 75 years (BMI 32.4 ± 3.9 kg/m2) with at least 2 factors of the metabolic syndrome participated in this study and were randomized into two groups: 1) high-protein caloric restriction (HP; n= 12) and 2) high-protein caloric restriction combined with dynamic-resistance training (HP+RT; n=14). Caloric intake was reduced by 500 kcal/d in all participants and protein intake equated 25-30% of total calories (~1.4 g/kg/d). Exercise training consisted of 3 session/week of resistance training on pulley machines. Outcome measures included total and trunk fat mass (FM), total and appendicular lean body mass (LBM), fasting glucose level, lipid profile and blood pressure. Our results showed that total and trunk FM (all p<0.0001) as well as fasting glucose (p<0.0001), triglycerides (p=0.002) and total cholesterol (p=0.03) levels decreased similarly in both groups. However, total (p=0.04) and appendicular (p=0.02) LBM decreased in the HP group only. Our data show that high-protein energy restriction improves health profile of obese elderly at high risk of chronic disease but needs to be combined with resistance training to maintain LBM.

Effects of Caloric Restriction with or without Resistance Training in Dynapenic-Overweight and Obese Menopausal Women: A MONET Study.

OBJECTIVE: The dynapenic (DYN)-obese phenotype is associated with an impaired metabolic profile. However, there is a lack of evidences regarding the effect of lifestyle interventions on the metabolic profile of individual with dynapenic phenotype. The objective was to investigate the impact of caloric restriction (CR) with or without resistance training (RT) on body composition, metabolic profile and muscle strength in DYN and non-dynapenic (NDYN) overweight and obese menopausal women. DESIGN: 109 obese menopausal women (age 57.9 ± 9.0 yrs; BMI 32.1 ± 4.6 kg/m2) were randomized to a 6-month CR intervention with or without a RT program. Participants were categorized as DYN or NDYN based on the lowest tertile of relative muscle strength in our cohort (< 4.86 kg/BMI). MEASUREMENTS: Body composition was measured by DXA, body fat distribution by CT scan, glucose homeostasis at fasting state and during an euglycemic-hyperinsulinemic clamp, fasting lipids, resting blood pressure, fasting inflammation markers and maximal muscle strength. RESULTS: No difference was observed between groups at baseline for body composition and the metabolic profile. Overall, a treatment effect was observed for all variables of body composition and some variables of the metabolic profile (fasting insulin, glucose disposal, triglyceride levels, triglycerides/HDL-Chol ratio and resting diastolic blood pressure) (P between 0.05 and 0.001). No Group X Treatment interaction was observed for variables of body composition and the metabolic profile. However, an interaction was observed for muscle strength; which significantly improved more in the CR+RT NDYN group (all P ≤ 0.05). CONCLUSIONS: In the present study, dynapenia was not associated with a worse metabolic profile at baseline in overweight and obese menopausal women. DYN and NDYN menopausal women showed similar cardiometabolic benefit from CR or CR+RT interventions. However, our results showed that the addition of RT to CR was more effective in improving maximal strength in DYN and NDYN obese menopausal women.

Variation in C-reactive protein following weight loss in obese insulin resistant postmenopausal women: is there an independent contribution of lean body mass?

BACKGROUND: We showed that obese insulin resistant postmenopausal women are characterized by higher lean body mass and elevated C-reactive protein. Although counterintuitive, we hypothesized that losses in muscle mass following caloric restriction and increase in muscle quality will be associated with improvements in glucose homeostasis through decreases in C-reactive protein. OBJECTIVES: To determine 1) if improvements in C-reactive protein concentrations occurs through losses in lean body mass; and 2) if decreases in C-reactive protein levels contribute to improvements in insulin sensitivity. METHODS: 50 postmenopausal women (body mass index>26 kg/m(²)) with impaired glucose disposal (<7.5 mg/kg/min) completed a 6-month caloric restriction program. Outcome measures were: Glucose disposal rate: M value (by hyperinsulinemic-euglycemic clamp), body composition (total, trunk, and appendicluar). LBM and FM by DXA), LBM index (LBM (kg)/height (m(2)), body fat distribution (VAT and SAT by CT scan) and plasma high-sensitive C-reactive protein (hsCRP) and interleukin-6 (Il-6). RESULTS: Significant correlations were observed between Δ hsCRP levels with Δ Il-6 (r=0.33, p≤0.05), Δ total LBM index (r=0.44, p≤0.01), Δ trunk LBM (r=0.38, p≤0.01) Δ SAT (r=0.35, p≤0.05) and ∆ glucose disposal rate (r=- 0.44, p≤0.01). After including all the correlated variables in Stepwise linear regression model, Δ LBM index was the only independent predictor of the reduction in hsCRP levels (R(2)=0.20, p≤0.01). CONCLUSION: Losses in total lean body mass are independently associated with improvements in inflammatory state (CRP levels) in obese postmenopausal women with impaired glucose disposal.

Effects of gestation on enzymes controlling aldosterone synthesis in the rat adrenal.

In the present study, the effects of gestation on various enzymes implicated in corticosteroid synthesis were evaluated in adrenal zona glomerulosa and zona fasciculata-reticularis of the Sprague-Dawley rat. The activity and expression of cholesterol side-chain cleavage cytochrome P450, 11beta-hydroxylase cytochrome P450, and aldosterone synthase cytochrome P450 (P450aldo) were analyzed. Plasma aldosterone levels were increased significantly at 22 days gestation (n = 10) and fell below the nonpregnant levels at 18-36 h postpartum (n = 11). The activity and expression of 11beta-hydroxylase cytochrome P450 and cholesterol side-chain cleavage cytochrome P450 were not modified by gestation. P450aldo activity increased at 14 days gestation (n = 4) and returned to the prepregnancy level at 2 weeks postpartum (n = 5). As shown by Northern blot analysis (n = 3), P450aldo messenger RNA increased significantly at 22 days gestation and decreased 18-36 h postpartum. We clearly demonstrated that elevated plasma aldosterone levels during pregnancy are associated with augmented activity and messenger RNA levels of P450aldo in the zona glomerulosa.

Increase in plasma steroid glucuronide levels in men from infancy to adulthood.

We studied the relationships between circulating steroid glucuronide concentrations and the changes in adrenal as well as testicular C-19 steroid secretion during pubertal development in men. Plasma levels of dehydroepiandrosterone and its sulfate, androst-5-ene-3 beta,17 beta-diol, androstenedione, testosterone, dihydrotestosterone, androstane-3 alpha,17 beta-diol and its glucuronide, and androsterone and its glucuronide were measured in 56 boys (aged 3-16 yr) and in normal men. There was a progressive and parallel increase in plasma dehydroepiandrosterone sulfate and dehydroepiandrosterone concentrations from age 7 to 15 yr, while plasma androstenedione and androst-5-ene-3 beta,17 beta-diol concentrations increased only at 11-12 yr. From age 13 yr to adulthood, a dramatic rise of testosterone was observed while there was no marked change in dihydrotestosterone or androstane-3 alpha,17 beta-diol. Between 3 and 11 yr of age, androsterone glucuronide increased from 0.68 +/- 0.24 (+/- SEM) to 2.25 +/- 0.59 ng/mL (P less than or equal to 0.01) and androstane-3 alpha,17 beta-diol glucuronide from 0.17 +/- 0.02 to 0.41 +/- 0.09 ng/mL (P less than or equal to 0.01). A further rise of both 5 alpha-reduced steroid glucuronides occurred when testosterone levels increased during puberty. Our data indicate that 5 alpha-reduced steroid glucuronides are good markers of peripheral transformation of adrenal and testicular C-19 steroids. In addition, since 5 alpha-reduced steroid glucuronides are detected before puberty, there must be a peripheral conversion of adrenal C-19 steroids into testosterone during prepubertal development.

Levels of plasma steroid glucuronides in intact and castrated men with prostatic cancer.

The levels of plasma dehydroepiandrosterone (DHEA), androst-5-ene-3 beta,17 beta-diol (delta 5-diol), testosterone (T), dihydrostestosterone (DHT), androstane-3 alpha,17 beta-diol (3 alpha-diol), androsterone (ADT), and the related glucuronide (G) derivatives were determined in intact and castrated men with prostatic cancer. The plasma concentrations of DHEA and DHEA-G were not significantly different in intact and castrated men while delta 5-diol as well as delta 5-diol-G were 50% lowered in castrated men. As expected, T and DHT concentrations were markedly lower in castrated men. These low plasma levels of T and DHT were accompanied by a decrease of 3 alpha-diol, ADT, T-G, 3 alpha-diol-G, and ADT-G levels. There was, in unoperated men, a positive correlation between the levels of DHEA and ADT-G as well as DHEA and DHEA-G, while T values were highly correlated with ADT-G and 3 alpha-diol-G levels. Furthermore, a significant relationship was found between DHEA and ADT-G as well as 3 alpha-diol-G in castrated men. Our data clearly demonstrate that ADT-G and 3 alpha-diol-G levels are more affected by castration than are the corresponding unconjugated steroids and suggest that these steroid glucuronides should be good markers of androgen metabolism. Moreover, the significant relationship between DHEA, ADT-G, and 3 alpha-diol-G in castrated men also suggests that approximately 30% of C-19 steroids from the adrenals are converted to T and DHT, which are further transformed into steroid glucuronides.

Are aerobically fit older individuals more physically active in their free-living time? A doubly labeled water approach.

There is considerable controversy regarding factors regulating free-living physical activity energy expenditure (PAEE) in older individuals. This component is highly variable, is difficult to accurately assess, and reflects both volitional and nonvolitional activities. We examined the association between maximal aerobic fitness (peak VO2) and free-living PAEE in older individuals. One hundred and eighty healthy older patients (96 females and 84 males) between 45-90 yr of age were studied. Total energy expenditure was measured from doubly labeled water. PAEE was calculated as the difference between total energy expenditure, resting metabolic rate, and estimated thermic effect of a meal. Peak VO2 was assessed from an exercise test to volitional fatigue. Fat mass and fat-free mass were assessed from dual energy x-ray absorptiometry. After correction for age, fat mass, and fat-free mass, significant correlations were observed between peak VO2 and PAEE for older males (r = 0.42; P < 0.0001) and females (r = 0.24; P < 0.05), although significant variation among volunteers was noted. When subjects were subdivided by tertiles based on their peak VO2 (liters per min), males with the highest peak VO2 showed greater free-living PAEE than individuals with low peak VO2 (P < 0.01). Similar results were observed in females (P < 0.05). Our results suggest a positive association between higher levels of peak VO2 and greater free-living PAEE in older individuals. This relationship is stronger in older men than in women. These additional energy-dissipating properties during their free-living time may serve to preserve leanness and buffer fat gain with age.