We have previously shown that 24 young lean men (12 pairs of identical twins) subjected to a standardized 353 MJ (84 000 kcal) overfeeding protocol over 100 days exhibited individual differences in ...body weight and composition gains. The mean (+s.d.) gains in fat mass (FM) and fat-free mass (FFM) were 5.4+1.9 kg and 2.7+1.5 kg for a total body energy (BE) gain of 221+75 MJ, representing 63% of the energy surplus consumed. We report here on the most important baseline correlates of these overfeeding-induced changes with the aim of identifying biomarkers of the response.
Baseline maximal oxygen uptake per kg body mass was negatively correlated with gains in weight, FM and BE (all P<0.05). Enzyme activities indicative of skeletal muscle oxidative potential correlated with gains in FM and BE (all P<0.05). Baseline thyroid-stimulating hormone levels in response to thyrotropin-releasing hormone stimulation correlated positively with changes in FM-to-FFM ratio (P<0.05). Plasma concentrations of androstenediol sulfate, dehydroepiandrosterone and 17-hydroxy pregnenolone were negatively correlated with gains in FM and BE (0.01<P<0.05), whereas the level of estrone was negatively correlated and androsterone glucoronide was positively correlated with FFM gains (P<0.05). Baseline leptin and abdominal fat cell size correlated positively with gains in weight, FM and BE (P<0.05). When compared with the six highest BE gainers, the six lowest gainers exhibited higher thermic effect of a meal (TEM) and plasma levels of total testosterone, cortisol, estradiol, androstenedione and androstenediol sulfate (all P<0.05). High baseline levels of total TEM, testosterone and androstenediol sulfate were associated with lower FM gains, whereas high baseline levels of FT4 and estrone were found in low-FFM gainers.
Although none of the variables exerted individually an overwhelmingly strong influence on overfeeding-induced changes, baseline FFM, maximal oxygen uptake, muscle oxidative capacity, androgens and leptin levels were the most consistent significant biomarkers of the responsiveness to chronic overfeeding.
The age-related decline in serum dehydroepiandrosterone (DHEA) and its sulfated ester (DHEA-S) has suggested that a relative deficiency of these steroids may be causally related to the development of ...chronic diseases generally associated with aging, including insulin resistance, obesity, cardiovascular disease, cancer, reductions of the immune defense, depression and a general deterioration in the sensation of well-being. The numerous studies which have focused on the link between DHEA and cardiovascular disease have generally been inconsistent, generating much debate and controversy on this issue. The present article is an analysis of studies on the relationship between endogenous DHEA or DHEA-S, obesity and cardiovascular disease risk, as well as DHEA treatment studies. Elevated plasma levels of free DHEA are associated with reduced obesity in both men and women, and with smaller abdominal body fat accumulations in men. However, contradictory results have been reported regarding the relationships between the sulfate ester DHEA-S and adiposity. Age differences in the populations studied may have been a confounding factor in these associations. On the other hand, DHEA-S level is not a predictor of cardiovascular disease endpoints in women, and appears to be a relatively weak one in men. DHEA intervention studies suggest that the effects of DHEA on serum lipids are, at best, modest or non-significant. The uncertainty as to whether endogenous and exogenous DHEA should be considered cardioprotective is related to discrepancies in the literature on this topic. Several studies may have been plagued by methodological problems such as low power, unreliable analytical methods, confounding factors or other differences in the populations studied. As a consequence, the original reports demonstrating dramatic effects of either endogenous or exogenous DHEA on cardiovascular disease risk have never been replicated. We propose that the effects of DHEA on cardiovascular disease risk (either favorable or unfavorable) should be considered to be much more modest than previously believed.
The present article summarizes some of the studies available on steroid hormone conversion through the specific expression of steroidogenic enzymes in adipose tissue (adipose tissue intracrinology) ...and discusses the potential impact of local adipose tissue steroid metabolism on the regulation of adipocyte function and other metabolic parameters. Several studies have demonstrated significant steroid hormone uptake and conversion by adipose tissues from various body sites and in various cell fractions. Activities and/or mRNAs of aromatase, 3beta-hydroxysteroid dehydrogenase (HSD), 3alpha-HSD, 11beta-HSD, 17beta-HSD, 7alpha-hydroxylase, 17alpha-hydroxylase, 5alpha-reductase and UDP-glucuronosyltransferase 2B15 have been detected in adipose tissue or adipose cells. These studies have demonstrated potentially important roles for these enzymes in obesity, central fat accumulation, and the metabolic syndrome. Future studies on adipose tissue intracrinology will contribute further to our understanding of steroid action in adipocytes.
Adipose tissue fibrosis is a relatively new notion and its relationship with visceral obesity and cardiometabolic alterations remains unclear, particularly in moderate obesity.
Our objective was to ...examine if total and pericellular collagen accumulation are relevant for the pathophysiology of visceral obesity and related cardiometabolic risk.
Surgical omental (OM) and subcutaneous (SC) fat samples were obtained in 56 women (age: 47.2±5.8 years; body mass index (BMI): 27.1±4.4 kg/m
). Body composition and fat distribution were measured by dual-energy X-ray absorptiometry and computed tomography, respectively. Total and pericellular collagen were measured using picrosirius red staining. CD68+ cells (total macrophages) and CD163+ cells (M2-macrophages) were identified using immunohistochemistry.
We found that only pericellular collagen percentage, especially in OM fat, was associated with higher BMI, body fat mass and adipose tissue areas as well as lower radiologic attenuation of visceral adipose tissue and altered cardiometabolic risk variables. Strong correlations between peri-adipocyte collagen percentage and total or M2-macrophage percentages were observed in both depots. Total collagen percentage in either compartment was not related to adiposity, fat distribution or cardiometabolic risk.
As opposed to whole tissue-based assessments of adipose tissue fibrosis, collagen deposition around the adipocyte, especially in the OM fat compartment is related to total and regional adiposity as well as altered cardiometabolic risk profile.
To examine the expression of selected transcription factors involved in adipogenesis and genes related to lipid metabolism in abdominal subcutaneous and omental fat tissue.
We obtained subcutaneous ...and omental adipose tissue samples from 40 women undergoing abdominal hysterectomies (age: 47+/-5 years; BMI 27.9+/-5.3 kg/m(2)). We measured isolated adipocyte size and metabolism, and detailed measures of body fat accumulation and body fat distribution were obtained (dual-energy X-ray absorptiometry and computed tomography, respectively).
Adipocyte size of both subcutaneous and omental fat were increased with higher body fat mass values, with similar regression slopes in each compartment. In contrast, with higher body fat mass values, fat accumulation was progressively higher in the subcutaneous than in the visceral fat compartment, suggesting hyperplasia in the subcutaneous fat compartment. Messenger RNA levels of CEBPalpha, PPARgamma2, SREBP1c and genes related to lipid metabolism (LPL, FABP4, DGAT1, DGAT2, PLIN and HSL) were significantly higher in subcutaneous than in omental fat tissue (P< or =0.001 for all). Only subcutaneous expression of these genes tracked with obesity levels as reflected by significant positive associations between subcutaneous fat CEBPalpha, SREBP1c and DGAT2 expression and total body fat mass (r=0.37, r=0.41, r=0.57, respectively, P< or =0,05), fat percentage (r=0.40, r=0.39, r=058, respectively, P< or =0,05) and subcutaneous adipose tissue area (r=0.36, r=0.38, r=0.58, respectively, P< or =0,05). Omental adipose tissue expression levels of these genes were not significantly related to adiposity measures.
These results show that in obese women, hyperplasia is predominant in the subcutaneous fat depot, whereas fat cell hypertrophy is observed both in the omental and subcutaneous compartments.
Objective
To determine whether an explained‐variance genetic risk score (GRS), with 36 single nucleotide polymorphisms (SNPs) previously associated with type 2 diabetes (T2D), is also associated with ...gestational diabetes mellitus (GDM), and with the progression to pre‐diabetes and T2D among women with prior GDM.
Design
A cohort study.
Setting
Clinical investigation unit of Laval University, Quebec, Canada.
Population
A cohort of 214 women with prior GDM and 82 controls recruited between 2009 and 2012.
Methods
Associations between the GRS and GDM.
Main outcomes measures
GDM and prevalence of pre‐diabetes and T2D.
Results
Women with prior GDM had a higher GRS compared with controls (38.6 ± 3.9, 95% CI 38.1–39.1, versus 37.4 ± 3.2, 95% CI 36.7–38.1; P < 0.0001). In women with prior GDM, the explained‐variance GRS was higher for pre‐diabetic women compared with women who remained normoglucotolerant at testing (1.21 ± 0.18, 95% CI 1.18–1.23, versus 1.17 ± 0.15, 95% CI 1.13–1.20; P < 0.0001). Similarly, women with T2D had a higher explained‐variance GRS compared with women with prior GDM who remained normoglucotolerant (1.20 ± 0.18, 95% CI 1.14–1.25, versus 1.17 ± 0.17, 95% CI 1.13–1.20; P < 0.0001). The predictive effects of the explained‐variance GRS, age, and body mass index (BMI), or the additive effects of the three variables, were tested for pre‐diabetes and T2D. We observed an area under the curve of 0.6269 (95% CI 0.5638–0.6901) for age and BMI, and adding the explained‐variance GRS into the model increased the area to 0.6672 (95% CI 0.6064–0.7281) for the prediction of pre‐diabetes.
Conclusions
An explained‐variance GRS is associated with both GDM and progression to pre‐diabetes and T2D in women with prior GDM.
Most of the interventional studies have investigated the impact of the diet on adiponectin and leptin concentrations only in men or in women. Consequently, it is still unknown whether the consumption ...of a healthy diet influences in a sex-specific manner these adipocytokines. We examined sex differences in the effects of the Mediterranean diet (MedDiet) on adiponectin and leptin concentrations, and determined whether changes in these adipocytokines are associated with changes in cardiovascular risk factors in both sexes.
Participants were 38 men and 32 premenopausal women (24-53 years) with slightly elevated low-density lipoprotein cholesterol concentrations (3.4-4.9 mmol/l) or total cholesterol/high-density lipoprotein cholesterol (HDL-C)⩾5.0. Adiponectin, leptin and cardiovascular risk factors were measured before and after a 4-week fully controlled isoenergetic MedDiet.
Adiponectin concentration decreased in response to the MedDiet, but this decrease reached statistical significance only in men (P<0.001 for men and P=0.260 for women; sex-by-time interaction, P=0.072). Adjustments for body weight or waist circumference did not change results obtained. Changes in adiponectin were positively associated with concomitant variations in HDL-C in men (r=0.52, P=0.003) and with variations in apolipoprotein A-1 and insulin sensitivity as calculated by both the homeostasis model assessment index for insulin sensitivity and Cederholm indices in women (respectively, r=0.44, P=0.021; r=0.79, P<0.001 and r=0.47, P=0.020). The MedDiet had no impact on leptin and the leptin-to-adiponectin ratio in both sexes.
Results suggest a sex difference in adiponectin response to the short-term consumption of the MedDiet, with only men experiencing a decrease. Also sex-specific patterns of associations between changes in adiponectin concentration and changes in cardiovascular risk factors were observed.
OBJECTIVE: Preliminary studies suggest that the menopause transition is associated with deleterious changes in body composition and abdominal fat distribution. Limitations of the methodology used in ...these studies, however, render their conclusions controversial. Thus, the present study used radiologic imaging techniques to examine the effect of menopausal status on body composition and abdominal fat distribution. DESIGN: Cross-sectional. SUBJECTS: Fifty-three healthy, middle-aged, premenopausal women (mean +/- SD; 47 +/- 3 y) and 28 early-postmenopausal women (51 +/- 4 y). MEASUREMENTS: Total and regional body composition by dual energy X-ray absorptiometry and abdominal fat distribution by computed tomography. RESULTS: No differences in total body fat-free mass or appendicular skeletal muscle mass were noted between groups. In contrast, total body fat mass was 28% higher (23 +/- 7 vs 18 +/- 7 kg) and percentage fat 17% higher (35 +/- 6 vs 30 +/- 9%; both P < 0.01) in postmenopausal women compared with premenopausal women. Postmenopausal women had a 49% greater intra-abdominal (88 +/- 32 vs 59 +/- 32 cm2; P < 0.01) and a 22% greater abdominal subcutaneous fat area (277 +/- 93 vs 227 +/- 108 cm2; P < 0.05) compared to premenopausal women. The menopause-related difference in intra-abdominal fat persisted (P < 0.05) after statistical adjustment for age and total body fat mass, whereas no difference in abdominal subcutaneous fat was noted. A similar pattern of differences in total and abdominal adiposity was noted in sub-samples of pre- and postmenopausal women matched for age or fat mass. CONCLUSION: Our data suggest that early-postmenopausal status is associated with a preferential increase in intra-abdominal fat that is independent of age and total body fat mass.
Objectives: Growth hormone (GH)-deficient individuals display increased adiposity that can be effectively reduced by GH therapy because of GH's lipolytic effects. However, similar GH treatments of ...individuals with idiopathic obesity (not associated with an endocrinopathy/syndrome) have had little success. We hypothesized that this form of obesity may be associated with GH resistance at the level of the adipocyte because of reduced GH receptor (GHR) expression. Subjects and methods: We studied GHR expression in omental and subcutaneous fat tissues from a cohort of 55 women ranging from lean to obese by various adiposity parameters. mRNA levels of total GHR and the dominant-negative truncated GHR1−279 (trGHR) form were assayed by quantitative reverse transcriptase-PCR. Associations between adiposity measures and GHR levels as well as trGHR/GHR ratios were analyzed. Results: Total GHR mRNA expression was 2–3-fold lower in omental as well as subcutaneous adipose tissues of obese compared with lean women (P0.05–0.001). Lean individuals expressed higher GHR mRNA levels in omental fat compared with subcutaneous (P0.01); in obese women, this depot-specific difference was lost. Omental and subcutaneous adipose GHR mRNA levels displayed significant negative correlations with a spectrum of indicators of obesity while, in subcutaneous fat, there was a significantly higher trGHR/GHR ratio with increasing adiposity (P0.05). Conclusion: These results support our hypothesis that, with obesity, there is lower GHR expression in the adipocyte, and suggest one possible explanation why GH supplementation is not an effective treatment for individuals with idiopathic obesity.
Summary
The aim of this cohort study was to compare body composition and regional body fat distribution between children exposed (GDM+) or unexposed (GDM−) in utero to gestational diabetes mellitus ...(GDM) and to investigate the association with the glycaemic and the insulin profile. Data from 56 GDM+ and 30 GDM− were analysed. Height, weight and waist circumference were measured. Total and regional body composition was measured by dual‐energy X‐ray absorptiometry. Insulin, glucose and HbA1c were obtained from a fasting plasma sample, and the HOMA‐IR index was calculated. anova was performed to compare adiposity measures between GDM+ and GDM−. Associations between the glycaemic and insulin profile and adiposity measures were studied using partial Pearson correlations. Mean age was 6.6 ± 2.3 years. Waist circumference, fat mass percentage, android fat mass, android fat mass percentage and android‐to‐gynoid fat mass ratio were higher among GDM+, and lean mass percentage was lower (P < 0.05). Among GDM+ children, body mass index (BMI) z score, waist circumference, fat mass percentage, android fat mass percentage and android‐to‐gynoid fat mass ratio were all positively correlated with HbA1C (r = 0.32–0.43, P < 0.05). Prenatal exposure to GDM is associated with increased total and abdominal adiposity. This increased adiposity observed among GDM+ children is associated with an altered glycaemic profile. This study is registered in the Clinical Trials.gov registry (NCT01340924).
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