Role of DHEA-S on body fat distribution: gender- and depot-specific stimulation of adipose tissue lipolysis

The objective of this work was to study the possible impact of DHEA-S on body fat distribution and the specific action of the hormone on lipolysis from visceral and subcutaneous human adipose tissue. First, a clinical evaluation was performed in 84 obese patients (29 men, 55 women), measuring serum DHEA-S, computed tomography (CT) anthropometric parameters of abdominal fat distribution. In a second experiment, subcutaneous and visceral adipose tissue samples were obtained from 20 obese patients (10 men, 10 women) and cultured in vitro under stimulation with DHEA-S to further assess a possible effect of this hormone on adipose tissue lipolysis. Serum DHEA-S was inversely and specifically associated with visceral fat area (VA) as assessed by CT in men and with waist-to-hip ratio in women. In vitro, DHEA-S increased lipolysis in women's subcutaneous adipose tissue at 2 h, while in men, the effect was evident in visceral tissue and after 24 h of treatment. In conclusion, DHEA-S contributes to gender-related differences in body fat distribution probably by a differential lipolytic action. We have demonstrated for the first time in vitro that DHEA-S stimulates lipolysis preferably in subcutaneous fat in women and in visceral fat in men.     

The relationship between aromatase activity and body fat distribution

The metabolism of androstenedione (A) to estrone (E1) and 5 alpha-reduced androgens was studied in stromal cells derived from human adipose tissue from different body sites. The tissue was obtained from non-obese patients undergoing cosmetic liposuction or at the time of surgery for reduction mammoplasty. The conversion of A to E1 per 1x 10(6) cells was between 6- and 30-fold greater in the upper thigh, buttock, and flank than in the abdomen. These differences were present in primary culture and persisted to at least the third subculture. Estrogen formation in breast adipose tissue was similar to that found in cells from abdominal fat. The formation of 5 alpha-reduced metabolites (5 alpha-androstenedione, androsterone, and dihydrotestosterone) varied from patient to patient but was similar in cells from different body sites. These studies show that the regional distribution of fat may influence the metabolism of androgens in adipose tissue, with upper body fat tending to form a lower ratio of estrogens to 5 alpha-reduced androgens than lower body fat.     

Growth and lipolysis of rat adipose tissue: effect of age, body weight, and food intake

The purpose of the present work was to study age- and weight-controlled rats to determine which is the primary factor in reducing the lipolytic response of free fat cells and which has the greater effect on the ratio of fat cells to nonfat cells in adipose tissue. The method for estimating fat cell and nonfat cell numbers is based on the analysis of adipose tissue and fat cell DNA and lipid. In adequately fed rats, epididymal adipocyte hyperplasia is complete between 9 and 14 wk of age. Chronic underfeeding delays, but does not eliminate, normal fat cell hyperplasia and is accompanied by a net loss in the nonfat cell population. During 9-14 wk of age, rat epididymal adipose tissue enlarges mainly through adipocyte hypertrophy. Total fat cells from the epididymal adipose tissue of control rats represent only 20-23% of the total cell population. Chronic underfeeding increases the percentage of fat cells in the fat pad from 23 to 28%. Noradrenaline-stimulated lipolysis is proportional to fat cell numbers but is inhibited when fat cell lipid increases to over 80% of fat pad wet weight. Rat age is apparently not primarily responsible for the decreased noradrenaline-stimulated lipolysis in fat cells of 350-g rats in vitro.     

Epicardial fat gene expression after aerobic exercise training in pigs with coronary atherosclerosis: relationship to visceral and subcutaneous fat

Epicardial adipose tissue (EAT) is contiguous with coronary arteries and myocardium and potentially may play a role in coronary atherosclerosis (CAD). Exercise is known to improve cardiovascular disease risk factors. The purpose of this study was to investigate the effect of aerobic exercise training on the expression of 18 genes, measured by RT-PCR and selected for their role in chronic inflammation, oxidative stress, and adipocyte metabolism, in peri-coronary epicardial (cEAT), peri-myocardial epicardial (mEAT), visceral abdominal (VAT), and subcutaneous (SAT) adipose tissues from a castrate male pig model of familial hypercholesterolemia with CAD. We tested the hypothesis that aerobic exercise training for 16 wk would reduce the inflammatory profile of mRNAs in both components of EAT and VAT but would have little effect on SAT. Exercise increased mEAT and total heart weights. EAT and heart weights were directly correlated. Compared with sedentary pigs matched for body weight to exercised animals, aerobic exercise training reduced the inflammatory response in mEAT but not cEAT, had no effect on inflammatory genes but preferentially decreased expression of adiponectin and other adipocyte-specific genes in VAT, and had no effect in SAT except that IL-6 mRNA went down and VEGFa mRNA went up. We conclude that 1) EAT is not homogeneous in its inflammatory response to aerobic exercise training, 2) cEAT around CAD remains proinflammatory after chronic exercise, 3) cEAT and VAT share similar inflammatory expression profiles but different metabolic mRNA responses to exercise, and 4) gene expression in SAT cannot be extrapolated to VAT and heart adipose tissues in exercise intervention studies.     

Gene expression changes with age in skin,adipose tissue,blood and brain

Background

Previous studies have demonstrated that gene expression levels change with age. These changes are hypothesized to influence the aging rate of an individual. We analyzed gene expression changes with age in abdominal skin, subcutaneous adipose tissue and lymphoblastoid cell lines in 856 female twins in the age range of 39-85 years. Additionally, we investigated genotypic variants involved in genotype-by-age interactions to understand how the genomic regulation of gene expression alters with age.

Results

Using a linear mixed model, differential expression with age was identified in 1,672 genes in skin and 188 genes in adipose tissue. Only two genes expressed in lymphoblastoid cell lines showed significant changes with age. Genes significantly regulated by age were compared with expression profiles in 10 brain regions from 100 postmortem brains aged 16 to 83 years. We identified only one age-related gene common to the three tissues. There were 12 genes that showed differential expression with age in both skin and brain tissue and three common to adipose and brain tissues.

Conclusions

Skin showed the most age-related gene expression changes of all the tissues investigated, with many of the genes being previously implicated in fatty acid metabolism, mitochondrial activity, cancer and splicing. A significant proportion of age-related changes in gene expression appear to be tissue-specific with only a few genes sharing an age effect in expression across tissues. More research is needed to improve our understanding of the genetic influences on aging and the relationship with age-related diseases.     

Korean and Caucasian overweight premenopausal women have different relationship of body mass index to percent body fat with age.

The aim of the study was to investigate in premenopausal women whether the relationship between percentage body fat (PBF) and body mass index (BMI; in kg/m2) differs between Korean Asians (Ko-As) living in Seoul, South Korea, and Caucasians (Ca) living in New York City. Healthy premenopausal women (50 Ko-As; 38 Ca), ages 22-50 yr, were studied. Weight, height, and PBF by dual-energy X-ray absorptiometry were measured. Total body dual-energy X-ray absorptiometry data were collected using GE-Lunar systems (Prodigy-Korea and DPXL-New York), and all scan analyses were performed by one technician in New York. Similar soft tissue phantoms were used for daily instrument calibrations at both sites. The relationship between PBF and BMI was assessed by multiple regression analysis with race, age, reciprocal of BMI (1/BMI), and a race-by-age interaction as the final independent variables. Race (P = 0.003) and 1/BMI (P < 0.001) were significantly related to PBF in this model. A significant race-by-age interaction (P = 0.039) indicated that the slope of the lines for PBF vs. age differed between Ko-As and Ca. This study demonstrates in a Ko-As sample that the BMI-fat relationship differs significantly from that in a comparable group of Caucasian women. Investigators who use BMI as an index of fatness should be aware of the well documented differences in the relationship of BMI and fatness across race/ethnic groups.     

Menarche age,fatness, and fat distribution in Hawaiian adolescents

Menarche age was assessed in 93 adolescent females in a sample of public schools in East Hawaii. Native Hawaiian girls had significantly lower reported age at menarche than non-Hawaiian classmates. Age at menarche was significantly correlated with total fatness as measured by the sum of six skinfolds in girls who had reached menarche at least 2 years previous to measurement. When fatness was controlled in comparisons, the ethnic differences were not significant. Fat distribution, independent of fatness, was also significantly related to age at menarche. Socioeconomic, cultural, and admixture variables were not significantly related to age at menarche. Adiposity appears to be both a cause and a consequence of early age at menarche, with the relationship dependent on the elapsed time between menarche and measurement. This suggests that studies relating body composition to age at menarche must carefully control for the time interval between measurement and the date of menarche. © 1996 Wiley-Liss, Inc.     

Sodium-lithium countertransport and body fat distribution.

The relationship between erythrocyte sodium-lithium countertransport (Na-Li CT) and body fat distribution is analyzed in a sample (n = 101) of normotensive and untreated hypertensive men participating in an epidemiological study of coronary heart disease risk factors. Na-Li CT is significantly and positively associated with both subscapular skinfold and waist to hip ratio, but not with triceps skinfold. The univariate correlation between Na-Li CT and blood pressure is diminished when adjusted for body mass index and waist to hip ratio. These findings support the existence of an association between Na-Li CT and central body fat distribution and suggest that the metabolic abnormalities associated with centrally distributed body fat could explain, at least in part, the association between Na-Li CT and blood pressure. The maximal velocity of the sodium-lithium countertransport (Na-Li CT) in erythrocytes has been reported to be directly associated with blood pressure and hypertension in numerous reports from both clinical and epidemiological studies. In most of these studies, indices of weight and/or adiposity (body mass index, in particular) have been shown to be among the most important correlates of Na-Li CT. Adiposity is an important determinant of blood pressure, and there is evidence suggesting that the patterning of the fat cells in the body is linked to a number of metabolic disturbances that could lead to hypertension and an increase in other CHD risk factors. The present report analyses the relationship between Na-Li CT and body fat distribution in a sample of normotensive and untreated hypertensive men participating in an epidemiological study.     

Relationships between body fat measured by DXA and subcutaneous adipose tissue thickness measured by Lipometer in adults

The aim of this study was to examine the relationships between body fat measured by DXA and subcutaneous adipose tissue layers (SAT-layers) measured by LIPOMETER in adult males (n=28) and females (n=53). Body height and mass were measured and BMI was calculated (kg/m2). Measurements of the thicknesses of SAT-layers by LIPOMETER were performed at 15 original body sites. Body composition was measured using DXA. Total body fat % measured by DXA was highly dependent on the SAT-layers in the upper back and inner thigh in males (87.1%, R(2)x100) and the lateral chest, biceps, and calf in females (78.5%, R(2)x100). There were gender differences in trunk fat mass and right hand and leg fat mass calculation using specific SAT-layers. In conclusion, our results indicate that there are close relationships between SAT-layers and body fat measured by DXA. However, there are big differences between genders.     

Diabetogenic diet-induced insulin resistance associates with lipid droplet proteins and adipose tissue secretome,but not with sexual dimorphic adipose tissue fat accumulation in Wistar rats

The role of sexual dimorphic adipose tissue fat accumulation in the development of insulin resistance is well known. However, whether vitamin A status and/or its metabolic pathway display any sex- or depot (visceral/subcutaneous)-specific pattern and have a role in sexual dimorphic adipose tissue development and insulin resistance are not completely understood. Therefore, to assess this, 5 weeks old Wistar male and female rats of eight from each sex were provided either control or diabetogenic (high fat, high sucrose) diet for 26 weeks. At the end, consumption of diabetogenic diet increased the visceral fat depots (p < 0.001) in the males and subcutaneous depot (p < 0.05) in the female rats, compared to their sex-matched controls. On the other hand, it caused adipocyte hypertrophy (p < 0.05) of visceral depot (retroperitoneal) in the females and subcutaneous depot of the male rats. Although vitamin A levels displayed sex- and depot-specific increase due to the consumption of diabetogenic diet, the expression of most of its metabolic pathway genes in adipose depots remained unaltered. However, the mRNA levels of some of lipid droplet proteins (perilipins) and adipose tissue secretory proteins (interleukins, lipocalin-2) did display sexual dimorphism. Nonetheless, the long-term feeding of diabetogenic diet impaired the insulin sensitivity, thus affected glucose clearance rate and muscle glucose-uptake in both the sexes of rats. In conclusion, the chronic consumption of diabetogenic diet caused insulin resistance in the male and female rats, but did not corroborate with sexual dimorphic adipose tissue fat accumulation or its vitamin A status.     

Endogenous estrogens and breast cancer a possible relationship between body fat distribution and estrogen availability

The growth of hormone-dependent human breast cancer is related to the activity of endogenous estrogens. The evidence for an etiological role of endogenous estrogens is still circumstantial. Life style and in particular dietary factors are held responsible for large geographic differences and time-trends in breast cancer incidence. The measurement of urinary estrogen metabolites and plasma estrogens has given no satisfactory explanation for the latter. The newly developed interest in the bioavailability of plasma sex steroids may offer a better understanding of the biology and epidemiology of breast cancer. Based on our observations on the relationship between plasma free fatty acids and estrogen-protein-binding and recently gained insight in the metabolic consequences of different types of body fat distribution we postulate that Western life style may act on breast cancer incidence through an influence on body fat distribution and resulting changes in sex steroid availability.     

Brown adipose tissue. VI. Amount, location, extent, and correlation with nutritional status in adult humans

Multilocular brown adipose tissue (BAT) is a versatile endocrine tissue involved in non-shivering thermogenesis, mitochondrial biogenesis, extracellular matrix homeostasis and signalling, and hibernation in hibernating animals. This study investigated the correlations between the amount and extent of BAT and nutritional status in adult humans. Samples of adipose tissue from nine body locations were taken from 107 consecutive autopsies in males and females, fixed in formalin, processed by routine methods and stained with hematoxylin-eosin. Based on the Quetelet index as a measure of nutritional status, the cases were divided into three groups: hypotrophic, eutrophic and hypertrophic (obese). We found significant sex and nutritional status differences in the frequencies of BAT positive cases. While no dependence on nutritional status was found in women, the frequencies of BAT positive cases in men were significantly different (41% in hypotrophy, 82% in eutrophy, and 64% in hypertrophy, P = 0.032). The distribution of BAT positive samples among sampled adipose tissue locations (positives for location and category/total positives for the category) were sex-independent, and showed that in hypertrophic cases, a large fraction of BAT is located in the periadrenal region, in agreement with a previous study by other authors. The present study also shows clear correlations between nutritional status and amount and extent of BAT in adult humans.     

Conversion of carbohydrate to fat in adipose tissue: an energy-yielding and, therefore, self-limiting process

A theoretical analysis of the energy metabolism associated with the conversion of glucose to fat is presented. In tissues where the pentose cycle furnishes some of the NADPH required for fatty acid synthesis, this conversion is an ATP-yielding process. In rat adipose tissue the maximal rate of glucose conversion to fat can be quantatively predicted on the basis of the tissue's ability to use the ATP which is generated in excess during this conversion. The energy-generating nature of this process provides the means for a type of regulation which depends on metabolic state and which, during fasting, contributes to the sparing of carbohydrate. Impairment of lipogenesis in the fasting state is attributed to a decrease in the activity of the malate cycle and to the presence of free fatty acids. However, rather than by inhibiting specific enzymes, it is by virtue of their quality as substrates for energy production that free fatty acids and their CoA derivatives appear to inhibit de novo lipogenesis. The regulatory phenomena discussed here may explain the failure of the attempts made to identify the rate-limiting step for de novo lipogenesis in adipose tissue.     

Biological distribution and significance of brown adipose tissue

1. The structure, location, identification and thermogenic function of brown adipose tissue is discussed before describing its distribution in animals. 2. With a few interesting exceptions, brown fat occurs almost exclusively in mammals. 3. This tissue has been positively identified in thirteen orders, but more thorough investigations are required before its absence can be confirmed in the remaining eight mammalian orders. 4. Factors influencing the amount and activity of brown fat seen between and within species are numerous, but some of the most important are body size, diet, environmental temperature, age and reproductive state. 5. The role brown fat, and the effects of impairments in its function, are described in relation to thermoregulation and the control of energy balance and body composition.     

Effects of white adipose tissue grafts on total body fat and cellularity are dependent on graft type and location

Surgical removal of body fat (lipectomy) triggers compensatory increases in nonexcised white adipose tissue (WAT), thus restoring adiposity levels in many species, including Siberian hamsters. In Siberian hamsters, when their lipectomized WAT is transplanted to another site (autologous grafts, no net change in body fat), healthy grafts result, but the lipectomy-induced compensatory increases in nonexcised WAT masses are exaggerated, an effect that apparently occurs only when the grafts contact intact WAT. When WAT is added to nonlipectomized hamsters to increase body fat, native WAT pads do not decrease. Thus WAT addition or removal-replacement does not induce compensatory WAT responses consistent with total body fat regulation as does WAT subtraction. Therefore, we tested whether the exaggerated response to lipectomy occurring with autologous WAT transplantation is dependent on graft site placement and whether the donor graft source [inguinal or epididymal WAT (IWAT, EWAT), sibling vs. nonsibling] affected body fat responses to WAT additions in nonlipectomized hamsters. Lipectomized hamsters received subcutaneous autologous EWAT grafts placed remotely from other WAT (ventrum) or in contact with intact WAT (dorsum), whereas intact hamsters received EWAT or IWAT grafts from sibling or nonsibling donors. The exaggerated response to lipectomy only occurred when grafts were in contact with intact WAT. EWAT, but not IWAT, additions to nonlipectomized siblings or nonsiblings increased native IWAT and retroperitoneal WAT mass but not EWAT mass compared with controls. Collectively, WAT transplantation to either lipectomized or nonlipectomized hamsters increased body fat contingent on graft contact with intact or native WAT.