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.     

Childbearing may increase visceral adipose tissue independent of overall increase in body fat

Objective: To examine whether childbearing is associated with increased visceral adiposity and whether the increase is proportionally larger than other depots. Methods and Procedures: This prospective study examined changes in adiposity assessed via computed tomography (CT) and dual‐energy X‐ray absorptiometry among 122 premenopausal women (50 black, 72 white) examined in 1995–1996 and again in 2000–2001. During the 5‐year interval, 14 women had one interim birth and 108 had no interim births. Multiple linear regression models estimated mean (95% confidence interval (CI)) 5‐year changes in anthropometric and adiposity measures by interim births adjusted for age, race, and changes in total and subcutaneous adiposity. Results: We found no significant differences between one interim birth and no interim births for 5‐year changes in weight, BMI, total body fat, subcutaneous adipose tissue, or total abdominal adipose tissue. Visceral adipose tissue increased by 40 and 14% above initial levels for 1 birth and 0 birth groups, respectively. Having 1 birth vs. 0 births was associated with a greater increase in visceral adipose tissue of 18.0 cm² (4.8, 31.2), P < 0.01; gain of 27.1 cm² (14.5, 39.7) vs. 9.2 cm² (4.8, 13.6), and a borderline greater increase in waist girth of 2.3 cm (0, 4.5), P = 0.05; gain of 6.3 cm (4.1, 8.5) vs. 4.0 cm (3.2, 4.8), controlling for gain in total body fat and covariates. Discussion: Pregnancy may be associated with preferential accumulation of adipose tissue in the visceral compartment for similar gains in total body fat. Further investigation is needed to confirm these findings and determine whether excess visceral fat deposition with pregnancy adversely affects metabolic risk profiles among women.     

Androgens and body fat distribution

An important sex difference in body fat distribution is generally observed. Men are usually characterized by the android type of obesity, with accumulation of fat in the abdominal region, whereas women often display the gynoid type of obesity, with a greater proportion of their body fat in the gluteal-femoral region. Accordingly, the amount of fat located inside the abdominal cavity (intra-abdominal or visceral adipose tissue) is twice as high in men compared to women. This sex difference has been shown to explain a major portion of the differing metabolic profiles and cardiovascular disease risk in men and women. Association studies have shown that circulating androgens are negatively associated with intra-abdominal fat accumulation in men, which explains an important portion of the link between low androgens and features of the metabolic syndrome. In women, the low circulating sex hormone-binding globulin (SHBG) levels found in abdominal obesity may indirectly indicate that elevated free androgens are related to increased visceral fat accumulation. However, data on non SHBG-bound and total androgens are not unanimous and difficult to interpret for total androgens. These studies focusing on plasma levels of sex hormones indirectly suggest that androgens may alter adipose tissue mass in a depot-specific manner. This could occur through site-specific modulation of preadipocyte proliferation and/or differentiation as well as lipid synthesis and/or lipolysis in mature adipocytes. Recent results on the effects of androgens in cultured adipocytes and adipose tissue have been inconsistent, but may indicate decreased adipogenesis and increased lipolysis upon androgen treatment. Finally, adipose tissue has been shown to express several steroidogenic and steroid-inactivating enzymes. Their mere presence in fat indirectly supports the notion of a highly complex enzymatic system modulating steroid action on a local basis. Recent data obtained in both men and women suggest that enzymes from the aldoketoreductase 1C family are very active and may be important modulators of androgen action in adipose tissue.     

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.     

Age-related decrease in cold-activated brown adipose tissue and accumulation of body fat in healthy humans

Brown adipose tissue (BAT) can be identified by (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) combined with X-ray computed tomography (CT) in adult humans. The objective of this study was to clarify the relationship between BAT and adiposity in healthy adult humans, particularly to test the idea that decreased BAT activity may be associated with body fat accumulation with age. One hundred and sixty-two healthy volunteers aged 20-73 years (103 males and 59 females) underwent FDG-PET/CT after 2-h cold exposure at 19 °C with light clothing. Cold-activated BAT was detected in 41% of the subjects (BAT-positive). Compared with the BAT-negative group, the BAT-positive group was younger (P < 0.01) and showed a lower BMI (P < 0.01), body fat content (P < 0.01), and abdominal fat (P < 0.01). The incidence of cold-activated BAT decreased with age (P < 0.01), being more than 50% in the twenties, but less than 10% in the fifties and sixties. The adiposity-related parameters showed some sex differences, but increased with age in the BAT-negative group (P < 0.01), while they remained unchanged from the twenties to forties in the BAT-positive group, in both sexes. These results suggest that decreased BAT activity may be associated with accumulation of body fat with age.     

Socioeconomic status, sex, age, and ethnicity as determinants of body fat distribution for Guatemalan children

The distribution of subcutaneous fat at the triceps and subscapular skinfold sites is described for four groups of children living in Guatemala. These groups are high socioeconomic status (SES) children of Ladino (mixed Spanish and Indian) ancestry, high SES children of European ancestry, low SES Ladino children, and very low SES Indian children. The method of Healy and Tanner (1981) is used, employing regression and principal components analysis of log transformed skinfold values to divide "fatness" into two uncorrelated variables: size (amount of fat) and shape (fat pattern). Significant differences exist between groups in size, with lower SES groups having less fat than higher SES groups. No significant difference in fat pattern exists between the high SES Ladino and high SES European children. Significant differences do exist between the high SES groups and the low SES groups. The relative amount of subscapular fat increases from the high SES Ladinos and high SES Europeans, to the low SES Ladinos, to the very low SES Indians. In the high SES European and high SES Ladino samples, girls have significantly more arm fat than boys. There is no significant difference in fat patterning between boys and girls in the two low SES samples. Finally, the relative amount of subscapular fat tends to increase with age in all four samples. These results indicate that fatness and fat patterning are independent anatomical characteristics, SES influences fat patterning; low SES children of both Ladino and Indian ancestry show greater reductions in arm fat than in trunk fat compared to high SES children, sexual dimorphism in fat patterning is SES dependent.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Comparing lipid remodeling of brown adipose tissue,white adipose tissue,and liver after one-week high fat diet intervention with quantitative Raman microscopy

Brown adipose tissue (BAT) consists of highly metabolically active adipocytes that catabolize nutrients to produce heat. Playing an active role in triacylglycerol (TAG) clearance, research has shown that dietary fatty acids can modulate the TAG chemistry deposition in BAT after weeks-long dietary intervention, similar to what has been shown in white adipose tissue (WAT). Our objective was to compare the influence of sustained, nonchronic dietary intervention (a 1-week interval) on WAT and interscapular BAT lipid metabolism and deposition in situ. We use quantitative, label-free chemical microscopy to show that 1 week of high fat diet (HFD) intervention results in dramatically larger lipid droplet (LD) growth in BAT (and liver) compared to LD growth in inguinal WAT (IWAT). Moreover, BAT showed lipid remodeling as increased unsaturated TAGs in LDs, resembling the dietary lipid composition, while WAT (and liver) did not show lipid remodeling on this time scale. Concurrently, expression of genes involved in lipid metabolism, particularly desaturases, was reduced in BAT and liver from HFD-fed mice after 1 week. Our data show that BAT lipid chemistry remodels exceptionally fast to dietary lipid intervention compared WAT, which further points towards a role in TAG clearance.     

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.     

Anatomical patterning of visceral adipose tissue: race, sex, and age variation

Objective: We tested sex, race, and age differences in the patterning of visceral adipose tissue (VAT) and subcutaneous adipose tissue. Research Methods and Procedures: Contiguous 1‐cm‐thick magnetic resonance (MR) images of the abdomen were collected from 820 African‐American and white adults. Repeated‐measures ANOVA was used to examine the effects of image location, sex, race, and age (≥50 vs. <50 years) on adipose tissue areas. Maximum VAT area was identified for each subject from the raw data. Results: Compared to women, men had greater total VAT volume (p < 0.0001), and their maximum VAT area occurred higher in the abdomen (p < 0.0001). Among white men, maximim VAT area most frequently occurred 5 to 10 cm above L4‐L5, whereas in the other groups, maximim VAT area most frequently occurred 1 to 4 cm above L4‐L5 (p < 0.0001). African‐American men had greater total VAT volume than African‐American women (p < 0.01), but this sex difference was only significant using single images cranial to L4‐L5 + 2 cm. Age‐related increases in VAT tended to be greatest 5 to 10 cm above L4‐L5 in men and near L4‐L5 in women. Discussion: A single MR image 5 to 10 cm above L4‐L5 may allow more accurate conclusions than the L4‐L5 image regarding group differences in visceral adiposity.     

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.     

Anthropometric measures, body composition, body fat distribution, and knee osteoarthritis in women

Objective: Increased BMI is a well‐recognized risk factor for radiographic knee osteoarthritis (rKOA); however, the contributions of the components of body composition, body fat distribution, and height to this association are not clear. Research Methods and Procedures: We examined 779 women ≥45 years of age from the Johnston County Osteoarthritis Project. Body composition was assessed using DXA, and rKOA was defined as Kellgren‐Lawrence grade ≥2. Logistic regression models examined the association between rKOA and the fourth compared with the first quartiles of anthropometric, body composition, and fat distribution measures adjusting for age, ethnicity, and prior knee injury. Results: The adjusted odds ratios and 95% confidence interval of BMI and weight were 5.27 (3.05, 9.13) and 5.28 (3.05, 9.16), respectively. In separate models, higher odds of rKOA were also found for fat mass [4.54 (2.68, 7.69)], percent fat mass [3.84 (2.26, 6.54)], lean mass [3.94 (2.22, 6.97)], and waist circumference [4.15 (2.45, 7.02)]. Waist‐to‐hip ratio was not associated with rKOA [1.45 (0.86, 2.43)], and percent lean mass was associated with lower odds [0.20 (0.11, 0.35)]. Taller women had higher odds of rKOA after adjustment for BMI [1.77 (1.05, 3.00)]. Discussion: This study confirms that BMI and weight are strongly associated with rKOA in women and suggests that precise measurements of body composition and measures of fat distribution may offer no advantage over the more simple measures of BMI or weight in assessment of risk of rKOA.