Traditional Anthropometric Parameters Still Predict Metabolic Disorders in Women With Severe Obesity

It is well established that fat distribution rather than the total quantity of fat is the major determinant of cardiovascular risk in overweight subjects. However, it is not known whether the concept of fat distribution still makes sense in severely obese subjects. Particularly, the role of visceral fat accumulation and/or of adipocyte hypertrophy in insulin resistance (IR) has not been studied in this population. Therefore, the aim of this study was to clarify the determinants of metabolic disorders in severely obese women. We performed a cross‐sectional study in 237 severely obese women (BMI >35 kg/m²). We assessed total body fat mass and fat distribution by anthropometric measurements (BMI and waist‐to‐hip ratio (WHR)) and by dual‐energy X‐ray absorptiometry (DXA). In 22 women, we measured subcutaneous and visceral adipocyte size on surgical biopsies. Mean BMI was 44 ± 7 kg/m² (range 35–77), mean age 37 ± 11 years (range 18–61). Lipid parameters (triglycerides, high‐density lipoprotein cholesterol) and IR markers (fasting insulin and homeostasis model assessment (HOMA) index) correlated with fat distribution, whereas inflammatory parameters (C‐reactive protein, fibrinogen) correlated only with total fat mass. An association was observed between android fat distribution and adipocyte hypertrophy. Visceral adipocyte hypertrophy was associated with both IR and hypertension, whereas subcutaneous fat‐cell size was linked only to hypertension. Our results obtained in a large cohort of women showed that fat distribution still predicts metabolic abnormalities in severe obesity. Furthermore, we found a cluster of associations among fat distribution, metabolic syndrome (MS), and adipocyte hypertrophy.     

Sex steroid hormones, sex hormone-binding globulin, and obesity in men and women.

Sex steroid hormones in both males and females have been closely related to the regulation of adiposity, either through direct or indirect physiological mechanisms. Evidence also suggests a direct relationship between sex hormones and risk factors for cardiovascular disease. In the present review article, we will discuss recent studies that have examined the complex interrelationships between sex hormones, SHBG, obesity and risk factors for cardiovascular disease. Male obesity and excess abdominal adipose tissue accumulation is associated with reductions in gonadal androgen and low adrenal C19 steroid concentrations. Reduced C19 steroids are also related to an altered metabolic risk factor profile including glucose intolerance and an atherogenic dyslipidemic state. However, the concomitant visceral obese state appears as a major correlate in these associations. In women, menopause-induced estrogen deficiency and increased androgenicity are associated with increased abdominal obesity and with the concomitant alterations in the metabolic risk profile. The accelerated accretion of adipose tissue in the intra-abdominal region coincident with the onset of menopause may explain part of the increased risk of cardiovascular disease in postmenopausal women. In both men and women, plasma levels of sex hormone-binding globulin are strong correlates of obesity and risk factors for cardiovascular disease, and more importantly, the relationships between low SHBG and altered plasma lipid levels appear to be independent from the concomitant increased levels of visceral adipose tissue. SHBG concentration may, therefore, represent the most important and reliable marker of the sex hormone profile in the examination of the complex interrelation of sex steroid hormones, obesity, and cardiovascular disease risk.     

Effects of serum irisin,neuregulin 4, and weight management on obese adolescent girls with polycystic ovary syndrome

The study is aimed at investigating the association of serum irisin, neuregulin 4 (NRG4), and anti-müllerian hormone (AMH) with adolescent obesity with polycystic ovary syndrome (PCOS) and the efficacy of weight management interventions. Serum levels of irisin, NRG4, AMH, sex steroid hormone, body mass index (BMI), serum insulin, and C-peptide were measured in 52 obese adolescent girls with PCOS (PCOS group) and 43 obese adolescent girls without PCOS (non-PCOS group). The levels of AMH, NRG4, serum irisin, sex steroid hormones, BMI, serum insulin, and C-peptide were evaluated in obese PCOS girls before and after one year weight management. The levels of AMH, serum insulin, NRG4, and total testosterone of PCOS group were significantly higher than those of non-PCOS group. On the contrary, serum irisin and serum C-peptide in PCOS group were significantly lower than that in non-PCOS group. The levels of fat mass, percent body fat, total testosterone, AMH, NRG4, and serum insulin in the obese girls with PCOS showed significant decreases compared with before weight management intervention. On the contrary, after one year of body weight management intervention, serum irisin and serum C-peptide was significantly increased. Adolescent obesity complicated with PCOS is significantly associated with glucose and lipid metabolism and sex steroid hormone disorders, but the exact pathophysiological and clinical features are highly variable. Weight management intervention can significantly improve the clinical symptoms and hematological indicators, serum irisin and NRG4 can be used as two essential biomarkers for evaluating weight management.     

Postmenopausal sex hormones in relation to body fat distribution

Being overweight or obese increases the risk of postmenopausal breast cancer. A potential reason may be the frequently observed positive association of BMI with endogenous sex hormones and its negative association with sex hormone-binding globulin (SHBG). The purpose of this study was to investigate whether a woman's body fat distribution shows a BMI-independent association with these breast cancer-related biomarkers. Performing cross-sectional analyses among 1,180 postmenopausal women, we assessed whether associations of surrogates for an abdominal (waist circumference; waist-to-hip ratio, WHR) and gluteofemoral (hip circumference) fat distribution with estrone, total and free estradiol, androstenedione, total and free testosterone, and SHBG changed after adjustment for, or stratification by, BMI. All anthropometric measures were positively associated with estrogens and free testosterone, and negatively with SHBG. After adjustment for BMI, associations of free estradiol, free testosterone, and SHBG with both waist circumference and WHR remained significant, but all initially significant associations with hip circumference were abolished. In stratified analyses, waist circumference and WHR correlated with free estradiol, free testosterone, and SHBG in women with a BMI < 30 kg/m(2) but not in women with a BMI ≥ 30 kg/m(2). The latter suggests that in obese women, a possibly unique effect of abdominal fat on these biomarkers may be masked by the already large amount of overall body fat. On the whole, our results indicate that waist circumference and WHR, but not hip circumference, are associated with SHBG and SHBG-related sex hormones (free estradiol and free testosterone) independently of BMI.     

Elevated serum 25(OH)D concentrations, vitamin D, and calcium intakes are associated with reduced adipocyte size in women

Recent studies have suggested a beneficial effect of vitamin D and calcium on adipocyte metabolism and the metabolic profile. Our objective was to examine associations of vitamin D intake, calcium and dairy products as well as serum 25(OH)D concentration with adiposity measures and adipocyte size in women. Omental and subcutaneous adipose tissue samples were obtained from 43 women undergoing gynecological surgeries. Adipocyte size was measured using adipocyte suspensions from collagenase-digested fat tissues. Total and visceral adiposity were assessed by dual-energy X-ray absorptiometry and computed tomography, respectively. Serum 25(OH)D was measured by radioimmmunoassay. Dietary intakes were assessed using a food frequency questionnaire. Women consuming two or more dairy product portions daily had smaller adipocytes in the omental depot compared to women consuming less than two portions daily (79 ± 12 vs. 94 ± 16 μm, P ≤ 0.01). Dietary intakes of calcium (r = -0.55) and vitamin D (r = -0.43) as well as serum 25(OH)D (r = -0.35) were also inversely and significantly associated with omental adipocyte size (P ≤ 0.05 for all). Dietary vitamin D intake was inversely associated with visceral adipose tissue area (r = -0.34, P ≤ 0.05). Serum 25(OH)D was also inversely associated with visceral adipose tissue area (r = -0.32) as well as with total adipose tissue area (r = -0.44), subcutaneous adipose tissue area (r = -0.36), BMI (r =-0.43) and total body fat mass (r = -0.41, P ≤ 0.05 for all). In conclusion, elevated dietary vitamin D intake and serum 25(OH)D values are related to lower visceral adiposity and omental adipocyte size in women.     

Interrelations between sex hormone-binding globulin (SHBG), plasma lipoproteins and cardiovascular risk

The incidence of coronary artery disease is significantly higher in men than in women, at least until menopause. This gender difference could be explained by the action of sex steroids on the lipoprotein profile. In prepubertal children, high-density lipoprotein (HDL) cholesterol and triglyceride levels are similar between sexes, while adult men have generally lower HDL cholesterol and higher triglyceride levels than premenopausal adult women. Most cross-sectional studies have reported that sex hormone binding globulin (SHBG) and testosterone levels correlate positively with HDL cholesterol levels between sexes. Thus SHBG by modulating the balance in the biodisposal of testosterone and estradiol, might have a profound effect on the risk of cardiovascular disease. However, adjustment for body weight and body fat distribution weakens the association between SHBG, testosterone and HDL cholesterol. The negative correlation of fasting insulin with SHBG and HDL cholesterol levels in both sexes, and some evidence that insulin is an inhibitor of SHBG production in vitro, has suggested that hyperinsulinism might negatively regulate SHBG and HDL levels. It remains to be determined whether the inverse relationship between SHBG and insulin levels is coincidental or has a causal effect on the increase of atherosclerosis. Decreased SHBG has been shown to be predictive of the incidence of non-insulin-dependent diabetes mellitus in women but not in men, and of subsequent development of cardiovascular disease and overall mortality in postmenopausal women. SHBG is an index of androgenism in women and of insulin-resistance in both sexes, and might be useful in epidemiological studies of cardiovascular risk. However, in men, SHBG is not predictive of the occurrence of cardiovascular disease. Whether SHBG might have an intrinsic protective effect on the arterial wall through SHBG-receptors is still highly speculative.     

Distribution and percentages of non-protein bound contraceptive steroids in human serum

It has been shown that albumin bound steroids are taken up by the rat brain in addition to nonprotein bound steroids and it has also been suggested that cortisol binding globulin (CBG) may facilitate progesterone uptake by the rat uterus but not the brain. Recently serum sex-hormone binding globulin (SHBG) has been identified in the cytoplasm of sex steroid target cells. Thus the distribution of synthetic steroids between various protein bound and nonprotein bound components in serum may influence their bioavailability at different target tissues. The authors employed a newly developed technique, centrifugal ultrafiltration-dialysis. The results showed that there are no differences in percentages of nonprotein bound ethinyl estradiol (EE2), and cyproterone acetate (CA) with respect to sex or serum SHBG and CBG binding capacities. However serum percentages of nonprotein bound norethisterone (NET) (p0.05) are significantly lower in women than in men. Also the percentages of nonprotein bound NET and D-norgestrel are both very much lower (p0.001) in serum from pregnant women when compared to nonpregnant women. These differences appear to be inversely related to serum SHBG binding capacity. The percentages of nonprotein bound NET and D-norgestrel in heat treated serum from men and nonpregnant women are identical and largely represent the contribution of albumin binding alone. In addition heat labile binding proteins do not appear to influence the percentages of nonprotein bound EE2 and CA and it can be inferred that EE2 and CA are almost exclusively bound by albumin in native serum; 98.5% of EE2 and 93% of CA are bound to albumin. In contrast the percentages of nonprotein bound NET and D-norgestrel in native serum are inversely related to SHBG binding capacity. This data indicate that the nonprotein bound and albumin bound factors of NET and D-norgestrel may vary by as much as 2-3 fold between women who are known to have subnormal or supranormal levels of serum SHBG binding capacity and it is suggested that measurements of serum SHBG binding capacity may provide a method of assessing the lowest effective dose of these 2 progestins in individual subjects to help reduce side effects associated with their use. Future studies should address the effect of serum steroid concentrations on the actual nonprotein bound serum concentrations and distribution of these progestins.     

Acquired liver fat is a key determinant of serum lipid alterations in healthy monozygotic twins

Objective: The effects of acquired obesity on lipid profile and lipoprotein composition in rare BMI‐discordant monozygotic (MZ) twin pairs were studied. Design and Methods: Abdominal fat distribution, liver fat (magnetic resonance imaging and spectroscopy), fasting serum lipid profile (ultracentrifugation, gradient gel‐electrophoresis, and colorimetric enzymatic methods), and lifestyle factors (questionnaires and diaries) were assessed in 15 BMI‐discordant (within‐pair difference [Δ] in BMI >3 kg/m²) and nin concordant (ΔBMI <3 kg/m²) MZ twin pairs, identified from two nationwide cohorts of Finnish twins. Results: Despite a strong similarity of MZ twins in lipid parameters (intra‐class correlations 0.42‐0.90, P < 0.05), concentrations of apolipoprotein B (ApoB), intermediate‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein 3a% (HDL3a%), and HDL3c% were higher (P < 0.05) and those of HDL cholesterol, HDL2‐C, and HDL2b% were lower (P < 0.01) in the heavier co‐twins of BMI‐discordant pairs. The composition of lipoprotein particles was similar in the co‐twins. When BMI‐discordant pairs were further divided into liver fat‐discordant and concordant (based on median for Δliver fat, 2.6%), the adverse lipid profile was only seen in those heavy co‐twins who also had high liver fat. Conversely, BMI‐discordant pairs concordant for liver fat did not differ significantly in lipid parameters. In multivariate analyses controlling for Δsubcutaneous, Δintra‐abdominal fat, sex, Δsmoking and Δphysical activity, Δliver fat was the only independent variable explaining the variation in ΔApoB, Δtotal cholesterol, and ΔLDL‐C concentration. Conclusions: Several pro‐atherogenic changes in the amounts of lipids but not in the composition of lipoprotein particles were observed in acquired obesity. In particular, accumulation of liver fat was associated with lipid disturbances, independent of genetic effects.     

Role of D327N sex hormone-binding globulin gene polymorphism in the pathogenesis of polycystic ovary syndrome

SHBG (sex hormone-binding globulin) is a transport protein specific for dihydrotestosterone, testosterone and estradiol. The missense mutation in exon 8 (GAC-->AAC) causing the amino acid exchange Asp-->Asn in codon 327 (D327N) correlates according to the published data with increased SHBG levels. We studied possible association of this polymorphism with polycystic ovary syndrome (PCOS) and anthropometric and biochemical parameters in 248 PCOS patients and 109 healthy control women. The D327N polymorphism (wild-type and variant allele) was detected using PCR-RFLP method (restriction enzyme Bbs-I). For statistical evaluation chi(2) test, Mann-Whitney test, ANCOVA, ANOVA (NCSS 2004, Statgraphics Plus v.5.1, USA) were used. There was no significant difference in genotype distribution between PCOS and controls (chi(2)=1.03, p=0.59). Moreover, we did not find an association of the variant allele with plasma SHBG level, steroid hormones, or screened parameters of lipid and glucose metabolism. In conclusion, the D327N polymorphism of the SHBG gene does not influence susceptibility to PCOS.     

Visceral adiposity,C-peptide levels,and low lipase activities predict HIV-dyslipidemia

Protease inhibitor-based highly active antiretroviral therapy (PI-HAART) has been implicated in dyslipidemia, peripheral insulin resistance, and abnormal adipose tissue deposition in human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome, or AIDS. In vitro evidence indicates that some PIs reduce adipocyte lipoprotein (LPL) and hepatic lipase (HL) expression and activities. We examined whether LPL and HL activities are reduced in HIV-infected patients with dyslipidemia. Fasting serum lipids, glucoregulatory hormones, and postheparin LPL and HL activities, as well as whole body and regional adiposity, were measured in 19 HIV-seronegative controls, 9 HIV+ patients naive to all anti-HIV medications, 9 HIV+ patients naive to PIs, 9 HIV+ patients with prior PI experience but not currently receiving PIs, and 47 HIV+ patients receiving PI-HAART. The PI-HAART group had low LPL and HL activities. However, multiple linear regression analysis indicated that low postheparin LPL activity contributed only partially to HIV-dyslipidemia. Central adiposity and high C-peptide levels (an indicator of high insulin secretion) were stronger predictors of HIV-dyslipidemia. Low LPL and HL activities, by themselves, were insufficient to explain HIV-dyslipidemia because the PI-naive group had low LPL and HL activities but had normal adiposity, C-peptide levels, and serum lipid and lipoprotein levels. HDL-cholesterol was lower in PI-HAART and PI-naive groups than seronegative controls and was directly associated with LPL activity. These findings suggest that HIV-dyslipidemia is mediated primarily by factors that influence triglyceride and lipoprotein synthesis (e.g., central adiposity and hyperinsulinemia) and mediated only partially by factors that influence triglyceride clearance (e.g., lipase activity).     

The effect of fat intake and antihypertensive drug therapy on serum lipid profile: a cross-sectional survey of serum lipids in male and female hypertensives

The present study aimed to investigate the effect of betablocker with diuretics therapy on serum cholesterol and high density lipoprotein (HDL-C) lipids in cross-sectional data (age, sex, weight, and body mass index (BMI), smoking/alcoholic consumption) and supplemented vegetarian low-fat diet with daily low fat energy intake, salt intake, duration of drug therapy, and serum protein as effective measures of lowering blood pressure among hypertensives in both males and females. Hypertensive patients on betablocker and/or thiazide therapy were compared in cross-section study with their age, blood pressure, fat intake, serum lipid profile, BMI, and serum albumin in males and females. Dietary fat intake and serum lipid profile were income related. Betablocker and diuretics therapy in combination with dietary fat intervention was beneficial for prolonged dyslipidemia control. Serum cholesterol level was main contributing factor dependent on BMI, duration of drug, and socio-economic factors. Fat intake contributed in hypertension and serum cholesterol levels. A cross-sectional data analysis showed beneficial effects of “low fat-salt-smoking-alcohol consumption and combined polyunsaturated fatty acid with antihypertensive therapy approach” to keep normal dyslipidemia and hypertension. Low fat intake, low salt, smoking, alcohol consumption, and combination of dietary oil supplements with lipid betablockers and diuretic modulators were associated with low hypertension and controlled dyslipidemia in Asian sedentary population.     

Postabsorptive VLDL‐TG Fatty Acid Storage in Adipose Tissue in Lean and Obese Women

Adipose tissue lipoprotein lipase (LPL) is a necessary enzyme for storage of very‐low‐density lipoprotein–triglyceride (VLDL‐TG), but whether it is a rate‐determining step is unknown. To test this hypothesis we included 10 upper‐body obese (UBO), 11 lower‐body obese (LBO), and 8 lean women. We infused ex vivo‐labeled VLDL‐¹⁴C‐TG and then performed adipose tissue biopsies to understand the relationship between VLDL‐TG storage and LPL activity in femoral and upper‐body subcutaneous fat. Both fractional tracer storage and rate of storage of the VLDL‐TG tracer were evaluated. VLDL‐TG storage was also examined as a function of regional adipose tissue blood flow (ATBF), insulin, VLDL‐TG turnover, regional fat mass, fat‐free mass (FFM), and fat cell size. LPL activity per adipocyte was significantly greater in obese than lean women but not significantly different per gram lipid. Both VLDL‐TG fractional tracer storage per kg lipid and VLDL‐TG storage rate per kg lipid were similar in abdominal and femoral fat in all three groups and were not significantly different between groups. Multiple regression analysis identified FFM and femoral fat mass as significant independent predictors of VLDL‐TG fractional tracer storage and insulin as a significant predictor of VLDL‐TG fatty acid storage rate. LPL activity, ATBF, and VLDL‐TG turnover did not predict VLDL‐TG storage. We conclude that lower FFM and greater plasma insulin are associated with greater VLDL‐TG deposition in abdominal subcutaneous and femoral fat. Greater femoral fat mass signals greater femoral VLDL‐TG storage. We suggest that the differences in VLDL‐TG storage in abdominal and femoral fat that occur with progressive obesity are regulated through mechanisms other than LPL activity.     

Long‐term effects of calorie restriction on serum sex‐hormone concentrations in men

Calorie restriction (CR) slows aging and consistently reduces circulating sex hormones in laboratory animals. However, nothing is known regarding the long‐term effects of CR with adequate nutrition on serum sex‐hormone concentration in lean healthy humans. In this study, we measured body composition, and serum total testosterone, total 17‐β‐estradiol, sex hormone–binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEA‐S) concentrations in 24 men (mean age 51.5 ± 13 years), who had been practicing CR with adequate nutrition for an average of 7.4 ± 4.5 years, in 24 age‐ and body fat–matched endurance runners (EX), and 24 age‐matched sedentary controls eating Western diets (WD). We found that both the CR and EX volunteers had significantly lower body fat than the WD volunteers (total body fat, 8.7 ± 4.2%; 10.5 ± 4.4%; 23.2 ± 6.1%, respectively; P = 0.0001). Serum total testosterone and the free androgen index were significantly lower, and SHBG was higher in the CR group than in the EX and WD groups (P ≤ 0.001). Serum 17β‐estradiol and the estradiol:SHBG ratio were both significantly lower in the CR and EX groups than in the WD group (P ≤ 0.005). Serum DHEA‐S concentrations were not different between the three groups. These findings demonstrate that, as in long‐lived CR rodents, long‐term severe CR reduces serum total and free testosterone and increases SHBG concentrations in humans, independently of adiposity. More studies are needed to understand the role of this CR‐mediated reduction in sex hormones in modulating the pathogenesis of age‐associated chronic diseases such as cancer and the aging process itself.     

Sex differences in human adipose tissues – the biology of pear shape

Women have more body fat than men, but in contrast to the deleterious metabolic consequences of the central obesity typical of men, the pear-shaped body fat distribution of many women is associated with lower cardiometabolic risk. To understand the mechanisms regulating adiposity and adipose tissue distribution in men and women, significant research attention has focused on comparing adipocyte morphological and metabolic properties, as well as the capacity of preadipocytes derived from different depots for proliferation and differentiation. Available evidence points to possible intrinsic, cell autonomous differences in preadipocytes and adipocytes, as well as modulatory roles for sex steroids, the microenvironment within each adipose tissue, and developmental factors. Gluteal-femoral adipose tissues of women may simply provide a safe lipid reservoir for excess energy, or they may directly regulate systemic metabolism via release of metabolic products or adipokines. We provide a brief overview of the relationship of fat distribution to metabolic health in men and women, and then focus on mechanisms underlying sex differences in adipose tissue biology.     

Changes in serum sex hormone-binding globulin and in serum non-sex hormone-binding globulin-bound testosterone during prepuberty in boys

Much evidence suggests that sex hormone-binding globulin (SHBG) influences the delivery of sex steroids to cells, probably by playing an important role in the distribution of serum sex hormones between SHBG-bound, albumin (HSA)-bound and free fractions. Recent evidence also suggests that HSA-bound testosterone (T), the major constituent of non-sex hormone-binding globulin-bound T, is biologically important. To examine the potential exposure of peripheral tissues to T during prepubertal years, the serum concentration of SHBG as well as the distribution of serum T in SHBG-bound, HSA-bound, free and non-SHBG-bound fractions was studied in 80 normal boys aged 0.5-14 yr, all at Tanner's stage G1 of sexual development. A gradual decrease in serum SHBG as a function of age was found without significant changes in the Ka of SHBG-dihydrotestosterone association. While regression analysis of serum total T vs age showed a 2.6-fold increase from 0.5 to 14 yr of age, those of non-SHBG-found, HSA-bound and free T vs age showed 8- to 9-fold increases during the same period. On the other hand, SHBG-bound T had only a 1.9-fold increase. Expressed as a function of serum total T, non-SHBG-bound T increased from 6.6 to 30.4%, the relative increment being greater for HSA-bound T than for free T. It is concluded that, with advancing age, there is a progressive increase in the T exposure of all tissues in normal prepubertal boys. It is speculated that, at the level of the central nervous system, this increase in serum bioavailable T could induce maturative changes in brain cells that result in the onset of puberty in normal boys.     

Subcutaneous fat accumulation shows a beneficial correlation with serum cholesterol in postmenopausal Japanese women

This study aimed to investigate whether accumulation of subcutaneous abdominal fat has a beneficial correlation with lipid metabolism in premenopausal and/or postmenopausal Japanese women. The study enrolled 146 premenopausal women, ranging in age from 19 to 54 years, and 82 postmeno-pausal women, ranging in age from 47 to 66 years. Fat distribution, including abdominal visceral fat area (VFA) and abdominal subcutaneous fat area (SFA), were measured in an outpatient clinic by magnetic resonance imaging. Homogeneity of the regression slopes for SFA to total cholesterol (P = 0.030), low-density lipoprotein cholesterol (P = 0.020), apolipoprotein B (apoB) (P = 0.001), and the ratio of apoB to apolipoprotein A-I (apoA-I) (P = 0.003) were not found between premenopausal and postmenopausal women, even after adjustment for both VFA and age. However, the regression slopes for VFA to all measured lipid parameters, as well as apolipoproteins, were homogeneous between the premenopausal and postmeno-pausal groups. Abdominal SFA in postmenopausal women correlated negatively with total cholesterol (P = 0.007), low-density lipoprotein cholesterol (P = 0.002), apoB (P < 0.001), and the ratio of apoB to apoA-I (P = 0.001), after adjustment for age and VFA, but this was not the case in premenopausal women. The mechanisms involved in the beneficial effects of subcutaneous fat accumulation in postmenopausal women remain obscure, but upregulated aromatase expression, derived from adipose tissue, may possibly improve lipid and apolipoprotein metabolism.     

Relationship of Adipocyte Size with Adiposity and Metabolic Risk Factors in Asian Indians

Background

Enlargement of adipocyte is associated with their dysfunction and alterations in metabolic functions.

Objectives

We evaluated the association of adipocyte size of subcutaneous and omental adipose tissue with body composition and cardiovascular risk factors in Asian Indians.

Methodology

Eighty (40 males and 40 females) non-diabetic adult subjects undergoing elective abdominal surgery were included. Pre-surgery evaluation included anthropometric measurements, % body fat by bioimpedance, abdominal fat area at L_2–3 level (computed tomography) and biochemical investigations (fasting blood glucose and insulin, lipids and hsCRP). During surgery, about 5 grams each of omental and subcutaneous adipose tissue was obtained for adipocyte size determination.

Results

Females had higher BMI, % body fat, skinfold thickness, total and subcutaneous abdominal fat area as compared to males. Overweight was present in 42.5% and 67.5%, and abdominal obesity in 5% and 52.5% males and females, respectively. Subcutaneous adipocyte size was significantly higher than omental adipocyte size. Omental adipocyte size correlated more strongly than subcutaneous adipocyte size with measures of adiposity (BMI, waist circumference, %BF), total and subcutaneous abdominal fat area and biochemical measures (fasting glucose, total cholesterol, triglycerides and HOMA-IR), the correlations being stronger in females. The correlation of adipocyte size with metabolic parameters was attenuated after adjusting for measures of adiposity.

Conclusion

Omental adipocyte size, though smaller than the subcutaneous adipocyte size, was more closely related to measures of adiposity and metabolic parameters. However, the relationship was not independent of measures of adiposity.     

No effect of menstrual cycle phase on basal very-low-density lipoprotein triglyceride and apolipoprotein B-100 kinetics

Dyslipidemia, manifested by increased plasma triglyceride (TG), increased total and LDL-cholesterol concentrations and decreased HDL-cholesterol concentration, is an important risk factor for cardiovascular disease. Premenopausal women have a less atherogenic plasma lipid profile and a lower risk of cardiovascular disease than men, but this female advantage disappears after menopause. This suggests that female sex steroids affect lipoprotein metabolism. The impact of variations in the availability of ovarian hormones during the menstrual cycle on lipoprotein metabolism is not known. We therefore investigated whether very-low-density lipoprotein (VLDL)-TG and VLDL-apolipoprotein B-100 (apoB-100) kinetics are different during the follicular (FP) and luteal phases (LP) of the menstrual cycle. We studied seven healthy, premenopausal women (age 27 +/- 2 yr, BMI 25 +/- 2 kg/m(2)) once during FP and once during LP. We measured VLDL-TG, VLDL-apoB-100, and plasma free fatty acid (FFA) kinetics by using stable isotope-labeled tracers, VLDL subclass profile by nuclear magnetic resonance spectroscopy, whole body fat oxidation by indirect calorimetry, and the plasma concentrations of lipoprotein lipase (LPL) and hepatic lipase (HL) by ELISA. VLDL-TG and VLDL-apoB-100 concentrations in plasma, VLDL-TG and VLDL-apoB-100 secretion rates and mean residence times, VLDL subclass distribution, FFA concentration and rate of appearance in plasma, whole body substrate oxidation, and LPL and HL concentrations in plasma were not different during the FP and the LP. We conclude that VLDL-TG and VLDL-apoB-100 metabolism is not affected by menstrual cycle phase.     

Sex differences in human adipose tissues - the biology of pear shape

ABSTRACT: Women have more body fat than men, but in contrast to the deleterious metabolic consequences of the central obesity typical of men, the pear-shaped body fat distribution of many women is associated with lower cardiometabolic risk. To understand the mechanisms regulating adiposity and adipose tissue distribution in men and women, significant research attention has focused on comparing adipocyte morphological and metabolic properties, as well as the capacity of preadipocytes derived from different depots for proliferation and differentiation. Available evidence points to possible intrinsic, cell autonomous differences in preadipocytes and adipocytes, as well as modulatory roles for sex steroids, the microenvironment within each adipose tissue, and developmental factors. Gluteal-femoral adipose tissues of women may simply provide a safe lipid reservoir for excess energy, or they may directly regulate systemic metabolism via release of metabolic products or adipokines. We provide a brief overview of the relationship of fat distribution to metabolic health in men and women, and then focus on mechanisms underlying sex differences in adipose tissue biology.     

Serum Leptin in Elderly People: Associations with Sex Hormones,Insulin, and Adipose Tissue Volumes

BAUMGARTNER, RICHARD N., ROBERT R. ROSS, DEBRA L. WATERS, WILLIAM M. BROOKS, JOHN E. MORLEY, GEORGE D. MONTOYA, AND PHILIP J. GARRY. Serum leptin in elderly people: associations with sex hormones, insulin, and adipose tissue volumes. Obes Res. Objective There are few data for associations of serum leptin with body fat, fat distribution, sex hormones, or fasting insulin in elderly adults. We hypothesized that the sex difference in serum leptin concentrations would disappear after adjustment for subcutaneous, but not visceral body fat. Serum leptin would not be associated with sex hormone concentrations or serum fasting insulin after adjusting for body fat and fat distribution. Research Methods and Procedures Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) volumes were measured using magnetic resonance imaging in a cross-sectional sample of 56 nondiabetic, elderly men and women aged 64 years to 94 years. Serum leptin, sex hormones (testosterone and estrone), sex hormone-binding globulin, and fasting insulin were also measured. Nine women were taking hormone replacement, and five men were clinically hypogonadal. Results Leptin was significantly associated with both SAT and VAT in each sex. Adjustment for SAT reduced the sex difference in leptin by 56%, but adjustment for VAT increased the difference by 25%. Leptin was not associated with serum estrone or hormone replacement therapy in the women, but had a significant, negative association with testosterone in the men that was independent of SAT, but not VAT. Leptin was significantly associated with fasting insulin in both sexes independent of age, sex hormones, sex hormone-binding globulin, VAT and SAT. Discussion Sex difference in serum leptin is partly explained by different amounts of SAT. Studies including both men and women should adjust for SAT rather than total body fat that includes VAT. The sex difference in serum leptin is not due to estrogen, but may be partly explained by testosterone. Testosterone is negatively associated with leptin in men, but the association is confounded with VAT. Leptin is associated with fasting insulin in non-diabetic elderly men and women independent of body fat, fat distribution. or sex hormones.