Differences of subcutaneous adipose tissue topography in type-2 diabetic (NIDDM) women and healthy controls

Women suffering from type-2 diabetes mellitus (non-insulin-dependent diabetes mellitus [NIDDM]) have more total body fat and upper body obesity compared with healthy controls. However, the standard measurement methods have disadvantages such as radiological burden, lack of precision, or high time consumption. A new optical device, the Lipometer, enables the noninvasive, quick, and save determination of the thickness of subcutaneous adipose tissue layers at any given site of the human body. The specification of 15 evenly distributed body sites allows the precise measurement of subcutaneous body fat distribution, so-called subcutaneous adipose tissue topography (SAT-Top). SAT-Tops of 20 women with clinically proven NIDDM and 122 healthy controls matched by age group were measured. In this paper, we describe the precise SAT-Top differences of these two groups and present the multidimensional SAT-Top information condensed in a two-dimensional factor plot and in a response plot of an artificial neural network. NIDDM women provide significantly lower leg SAT-Top and significantly higher upper trunk SAT-Top development ("apple"-type) compared with their healthy controls.     

Android subcutaneous adipose tissue topography in lean and obese women suffering from PCOS: comparison with type 2 diabetic women

The new optical device, the lipometer, enables the noninvasive, quick, safe, and precise determination of the thickness of subcutaneous adipose tissue (SAT) layers at any given site of the human body. Fifteen anatomically well-defined body sites from neck to calf describe a SAT topography (SAT-Top) like an individual "fingerprint" of a subject. This SAT-Top was examined in 16 women with polycystic ovary syndrome (PCOS) and compared to the body fat distribution of 87 age-matched healthy controls and 20 type-2 diabetic women. SAT-Top differences of these three groups were described and, to render the possibility of visual comparison, the 15-dimensional body fat information was condensed to a two-dimensional factor plot by factor analysis. All PCOS patients had an android body fat distribution with significantly thinner SAT layers on the legs as compared to healthy controls. Moreover, a hierarchical cluster analysis resulted in two distinctly different groups of PCOS women, a lean (PCOSL) and an obese (PCOSO) cluster: compared to healthy women, lean PCOS patients had significantly lower total SAT development, even though height, weight, and body mass index did not deviate significantly. Especially on the legs, their SAT layers were significantly lowered, indicating a more "apple-like" fat distribution type. Obese PCOS women showed a SAT-Top pattern very similar to that of women with type-2 diabetes, although the mean age difference between these groups was more than 30 years. Compared to healthy controls, the SAT-Top of these obese PCOS patients was strongly shifted into the android direction, appearing as "super-apples" with a significantly increased upper trunk obesity to 237.8% and a significantly decreased leg SAT development to 79.8%.     

Subcutaneous adipose tissue pattern in lean and obese women with polycystic ovary syndrome

The new optical device, Lipometer, permits the noninvasive, quick, safe, and precise measurement of the thickness of subcutaneous adipose tissue (SAT) layers at any given site of the human body. Fifteen anatomically well-defined body sites from neck to calf describe the SAT topography (SAT-Top) like an individual "fingerprint." SAT-Top was examined in 33 women with polycystic ovary syndrome (PCOS), in 87 age-matched healthy controls and in 20 Type-II diabetic women. SAT-Top differences of these three groups were described, and, based on a hierarchical cluster analysis, two distinctly different groups of PCOS women, a lean (PCOS(L)) and an obese (PCOS(O)) cluster, were found. For visual comparison of the different types of body fat distribution, the 15-dimensional body fat information was condensed to a two-dimensional factor plot by factor analysis. For comparison of the PCOS like body fat distribution with the "healthy" fat pattern, the (previously published) SAT-Top results of 590 healthy women and men (20-70 years old) and 162 healthy girls and boys (7-11 years old) were added to the factor plot. PCOS(O) women showed a SAT-Top pattern very similar to that of women with Type-II diabetes, even though the diabetic women were on average 30 years older. Compared with their healthy controls, SAT-Top of these PCOS(O) patients was strongly skewed into the android direction, providing significantly decreased leg SAT development and significantly higher upper body obesity. Compared with healthy women, PCOS(L) patients had significantly lower total SAT development (even though height, weight, and body mass index did not deviate significantly), showing a slightly lowered amount of body fat in the upper region and a highly significant leg SAT reduction. This type of fat pattern is the same as found in girls and boys before developing their sex specific body fat distribution. We conclude that women with PCOS develop an android SAT-Top, but compared in more detail, we found two typical types of body fat distribution: the "childlike" SAT pattern in lean PCOS patients, and the "diabetic" body fat distribution in obese PCOS women.     

Orthogonal factor coefficient development of subcutaneous adipose tissue topography (SAT-Top) in girls and boys

The new optical device Lipometer allows noninvasive, quick, and safe determination of the thickness of subcutaneous adipose tissue (SAT) layers (in mm) at any site of the human body. The specification of 15 evenly distributed body sites enables the precise measurement of subcutaneous body fat distribution, so-called subcutaneous adipose tissue topography (SAT-Top). SAT-Top was measured in 980 children aged 7-19 years. In this paper we describe the degree to which SAT-Top body sites are intercorrelated. We consider whether a meaningful reduction of data is possible using factor analysis, which factors can be extracted, and how SAT-Top data of children can be added to a factor value plot, depicting the essential results of age-dependent subcutaneous fat development. SAT layers situated on the same body area provide correlation coefficients up to +r = 0.91. Two factors are extracted: factor 1, containing all upper body sites (from neck to hip); and factor 2, consisting of all leg body sites. When all 980 children are divided into three age groups in a factor value plot, the first age group (7-11 years) shows almost equal SAT-Top development in boys and girls. Afterwards, for the consecutive age groups 2 (11-15 years) and 3 (15-19 years), the age-dependent subcutaneous fat development of boys and girls progresses into nearly orthogonal directions.     

Adipose tissue distribution in relation to insulin resistance in type 2 diabetes mellitus

Insulin resistance (IR) is typically more severe in obese individuals with type 2 diabetes (T2DM) than in similarly obese non-diabetics but whether there are group differences in body composition and whether such differences contribute to the more severe IR of T2DM is uncertain. DEXA and regional CT imaging were conducted to assess adipose tissue (AT) distribution and fat content in liver and muscle in 67 participants with T2DM (F39/M28, age 60 +/- 7 yr, BMI 34 +/- 3 kg/m(2)) and in 35 similarly obese, non-DM volunteers (F20/M15, age 55 +/- 8 yr, BMI 33 +/- 2 kg/m(2)). A biopsy of subcutaneous abdominal AT was done to measure adipocyte size. A glucose clamp was performed at an insulin infusion of 80 mU x min(-1) x m(-2). There was more severe IR in T2DM (6.1 +/- 2.3 vs. 9.9 +/- 3.3 mg x min(-1) x kg FFM(-1); P < 0.01). Group comparisons of body composition parameters was performed after adjusting for the effect of age, gender, race, height and total fat mass (FM). T2DM was associated with less leg FM (-1.2 +/- 0.4 kg, P < 0.01), more trunk FM (+1.1 +/- 0.4 kg, P < 0.05), greater hepatic fat (P < 0.05), and more subfascial adipose tissue around skeletal muscle (P < 0.05). There was a significant group x sex interaction for VAT (P < 0.01), with greater VAT in women with T2DM (P < 0.01). Mean adipocyte size (AS) did not significantly differ across groups, and smaller AS was associated with increased leg FM, whereas larger AS was related to more trunk FM (both P < 0.05). Group differences in IR were less after adjusting for group differences in leg FM, trunk FM, and hepatic fat, but these adjustments only partially accounted for the greater severity of IR in T2DM. In summary, T2DM, compared with similarly obese nondiabetic men and women, is associated with less leg FM and greater trunk FM and hepatic fat.     

Evaluation of risk profiles by subcutaneous adipose tissue topography in obese juveniles

Objective: To compare subcutaneous adipose tissue topography (SAT‐top) in obese juveniles with age‐matched normal‐weight controls. Research Methods and Procedures: The optical device LIPOMETER (European Patent EP 0516251) enables the non‐invasive, rapid, safe, and precise measurement of the thickness of subcutaneous adipose tissue. Fifteen defined body sites (1 = neck to 15 = calf) characterize the individual SAT‐top like an individual fingerprint. SAT‐top of 1351 juveniles (obese: 42 boys, 59 girls, normal weight: 680 boys, 570 girls) from 7 to 19 years of age were measured. For visual comparison, the 15‐dimensional SAT‐top information was condensed by factor analysis into a two‐dimensional factor plot. Results: Both female and male obese juveniles had markedly increased adipose tissue layers at 7 = upper abdomen, 8 = lower abdomen, 5 = front chest, and 6 = lateral chest. The pubertal changes of body shape and fat distribution of the normal‐weight boys and girls (boys show thinner adipose tissue layers on their legs, whereas girls had thicker adipose tissue layers at the extremities) were not seen in the obese group. Independently of age and sex, all of the obese juveniles showed a similar, more android body fat distribution with increased trunk fat. Discussion: SAT‐top of the obese juveniles is similar to that of patients with type 2 diabetes, polycystic ovary syndrome, and coronary heart disease. Patients with these metabolic disorders and obese juveniles are located in the factor plot in the same area. This body shape may indicate a risk profile for developing polycystic ovary syndrome (women), type 2 diabetes, and early atherosclerosis (both sexes).     

Meal Fat Storage in Subcutaneous Adipose Tissue: Comparison of Pioglitazone and Glipizide Treatment of Type 2 Diabetes

Treatment of type 2 diabetes (T2DM) with pioglitazone changes abdominal fat in the opposite direction as treatment with glipizide. To determine whether these two medications affect adipose tissue meal fatty acid storage differently we studied 19 T2DM treated with either pioglitazone (n = 8) or glipizide (n = 11) and 11 non‐DM control subjects matched for age, BMI, abdominal and leg fat. A breakfast mixed meal containing [1‐¹⁴C]triolein was given and abdominal and femoral subcutaneous (sc) adipose tissue biopsies were collected 6 and 24 h later to measure meal fatty acid storage. The portion of meal fatty acids stored in upper body sc and lower body sc adipose tissue did not differ between non‐DM and T2DM subjects either at 6 or 24 h. Likewise, meal fatty acid storage did not differ between the T2DM participants treated with pioglitazone or glipizide. We conclude that meal fatty acid storage in upper body and lower body sc adipose tissue is not abnormal in T2DM patients treated with pioglitazone or glipizide.     

Detecting Body Fat–A Weighty Problem BMI versus Subcutaneous Fat Patterns in Athletes and Non-Athletes

We aimed to describe the relationship between BMI and the subcutaneous adipose tissue topography within young athletes and non-athletic controls, to comparatively evaluate the diagnostic powers of subcutaneous adipose tissue thicknesses at different body sites, furthermore to explore appropriate cut-offs to discriminate between athletes and controls. Measurements were determined in 64 males and 42 females, who were subsequently separated into two even groups (athletes and non-athletes). The optical device LIPOMETER was applied at standardised body sites to measure the thickness of subcutaneous adipose tissue layers. To calculate the power of the different body sites and the BMI to discriminate between athletes and non-athletes, receiver operating characteristic curve analysis was performed. In men, the neck (optimal cut-off value 2.3 mm) and trunk (optimal cut-off value 15.5 mm) provided the strongest discrimination power: with 90.6% (58 of 64) of the subjects being correctly classified into athletes or non-athletes. Discrimination power of the BMI values was 64.1% (41 of 64 were correctly classified). In women, the upper back (optimal cut-off value 3.3 mm) and arms (optimal cut-off value 15.9 mm) provided the strongest discrimination power with 88.1% (37 of 42 being correctly classified). When using BMI to discriminate between athletes and non-athletes only 52.4% (22 of 42) were correctly classified. These results suggest that compared to BMI levels, subcutaneous fat patterns are a more accurate way of discriminating between athletes and non-athletes. In particular the neck and the trunk compartment in men and the upper back and arms compartment in women, were the best sites to discriminate between young athletes and non-athletes on the basis of their fat patterns.     

Sex-specific differences in leg fat uptake are revealed with a high-fat meal

The mechanism(s) by which sex specific differences in regional body fat distribution develop are not known. We assessed the effects of a high-fat (HF) meal on fatty acid oxidation and uptake into regional fat depots using isotopic tracers and adipose biopsies. Thirty men (BMI 23.6 +/- 0.3 kg/m(2)) and 29 women (BMI 22.4 +/- 0.3 kg/m(2)) received a meal containing [(3)H]triolein. Twelve of the men and 13 of the women received an additional 80 g of triolein in the meal (HF) and the remainder received a normal-fat (NF) meal. Adipose tissue lipoprotein lipase (LPL) activity was measured in the fed and fasted state. After 24 h, meal fatty acid uptake into subcutaneous adipose tissue was assessed. The efficiency of meal fat uptake into upper body subcutaneous fat was similar in both sexes, but women had a greater leg fat uptake, especially in response to a HF meal (P < 0.0001). A correlation between fed-state LPL activity and meal fat uptake was found in both upper and lower body fat (P < 0.0001, r = 0.69). These studies show that, in times of net fat storage, women preferentially increase uptake in leg adipose tissue, and this is likely mediated by fed-state LPL activity.     

Isotope tracer measures of meal fatty acid metabolism: reproducibility and effects of the menstrual cycle

Oxidation and adipose tissue uptake of dietary fat can be measured by adding fatty acid tracers to meals. These studies were conducted to measure between-study variability of these types of experiments and assess whether dietary fatty acids are handled differently in the follicular vs. luteal phase of the menstrual cycle. Healthy normal-weight men (n = 12) and women (n = 12) participated in these studies, which were block randomized to control for study order, isotope ([3H]triolein vs. [14C]triolein), and menstrual cycle. Energy expenditure (indirect calorimetry), meal fatty acid oxidation, and meal fatty acid uptake into upper body and lower body subcutaneous fat (biopsies) 24 h after the experimental meal were measured. A greater portion of meal fatty acids was stored in upper body subcutaneous adipose tissue (24 +/- 2 vs. 16 +/- 2%, P < 0.005) and lower body fat (12 +/- 1 vs. 7 +/- 1%, P < 0.005) in women than in men. Meal fatty acid oxidation (3H2O generation) was greater in men than in women (52 +/- 3 vs. 45 +/- 2%, P = 0.04). Leg adipose tissue uptake of meal fatty acids was 15 +/- 2% in the follicular phase of the menstrual cycle and 10 +/- 1% in the luteal phase (P = NS). Variance in meal fatty acid uptake was somewhat (P = NS) greater in women than in men, although menstrual cycle factors did not contribute significantly. We conclude that leg uptake of dietary fat is slightly more variable in women than in men, but that there are no major effects of menstrual cycle on meal fatty acid disposal.     

Effects of a hyperbaric environment on subcutaneous adipose tissue topography (SAT-top)

The physiological reactions of the body in scuba diving situation can be simulated in a pressure chamber by increasing the ambient pressure. In this study the influence of a hyperbaric environment of 6 bar on the changes of the subcutaneous adipose tissue (SAT) thicknesses on different body sites in 68 voluntary men with undersea diving experience was investigated. Measurements of SAT-topography (SAT-Top) were performed with the optical device Lipometer before and after hyperbaric exposure. We observed a significant increase of the SAT-layers of the upper body zones, upper abdomen (+24.5%), lower abdomen (+21%) and front chest (+19%) after hyperbaric exposure. This increase of volume can be assumed to the nitrogen accumulation in fat cells at increased ambient pressures. In conclusion we describe for the first time in detail the influence of a hyperbaric environment on quantitative and topographic changes of SAT.     

Body Compartment and Subcutaneous Adipose Tissue Distribution - Risk Factor Patterns in Obese Subjects

The purpose of this study was to investigate whether upper body obesity and/or visceral obesity are related to cardiovascular risk factors among severely obese subjects, phenomena that have previously been reported in more heterogeneous body weight distri -buttons. 2450 severely obese men and women aged 37 to 59 years, with a body mass index of 39 ± 4.5 kg/m² (mean ± SD) were examined cross-sectionally. Eight cardiovascular risk factors were studied in relation. to the following body composition indicators: four trunk and three limb circumferences, along with weight, height and sagittal trunk diameter. From the latter three measurements lean body mass (LBM, i.e., the non-adipose tissue mass) and the masses of subcutaneous and visceral adipose tissue were estimated by using sex-specific prediction equations previously calibrated by computed tomography. Two risk factor patterns could be distinguished: 1. One body compartment- risk factor pattern in which the subcutaneous adipose tissue (AT) mass and, in particular, the visceral AT mass were positively related to most risk factors while the lean body mass was negatively related to some risk factors. 2. One subcutaneous adipose tissue distribution- risk factor pattern in which the neck circumference was positively and the thigh circumference negatively related to several risk factors. It is concluded that lean body mass (LBM), visceral and subcutaneous adipose tissue masses as well as neck and thigh circumferences, used as indices of subcutaneous adipose tissue distribution, are independently related to cardiovascular risk factors in severely obese men and women.     

Sex dimorphism and depot differences in adipose tissue function

Obesity, characterized by excessive adiposity, is a risk factor for many metabolic pathologies, such as type 2 diabetes mellitus (T2DM). Numerous studies have shown that adipose tissue distribution may be a greater predictor of metabolic health. Upper-body fat (visceral and subcutaneous abdominal) is commonly associated with the unfavorable complications of obesity, while lower-body fat (gluteal–femoral) may be protective. Current research investigations are focused on analyzing the metabolic properties of adipose tissue, in order to better understand the mechanisms that regulate fat distribution in both men and women. This review will highlight the adipose tissue depot- and sex-dependent differences in white adipose tissue function, including adipogenesis, adipose tissue developmental patterning, the storage and release of fatty acids, and secretory function. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease.     

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.     

Meal fatty acid uptake in adipose tissue: gender effects in nonobese humans

We tested for gender differences in dietary fatty acid metabolism in 12 nonobese men and 12 nonobese women using the meal fatty acid tracer/adipose tissue biopsy study design. In addition to determining body composition, measurements of regional adipose tissue lipoprotein lipase activity, blood flow, and fat cell size were performed to place the meal fatty acid kinetic studies in perspective. Twenty-four hours after ingesting the test meal, the concentration of meal fatty acids was greater (P < 0.05) in abdominal subcutaneous than in thigh adipose tissue in both men (0. 61 +/- 0.12 vs. 0.45 +/- 0.09 mg/g) and women (0.59 +/- 0.10 vs. 0. 43 +/- 0.05) but was not different between men and women. A greater percentage of dietary fat was stored in subcutaneous adipose tissue in women than in men (38 +/- 3 vs. 24 +/- 3%, respectively, P < 0. 05), and a greater portion of meal fatty acid disposal was unaccounted for in men. Significant gender differences in regional adipose tissue blood flow after meal ingestion were noted; the differences were in the direction that could support greater nutrient storage in lower body fat in women.     

Regional uptake of meal fatty acids in humans

Two protocols were performed to study meal fatty acid metabolism. In protocol 1, 14 patients scheduled for elective intra-abdominal surgery (11 undergoing bariatric surgery for severe obesity) consumed a meal containing [3H]triolein in the evening before surgery. This allowed us to measure adipose tissue lipid specific activity (SA) in mesenteric and omental, deep and superficial abdominal subcutaneous adipose tissue. Intra-abdominal adipose tissue lipid SA was greater than subcutaneous lipid SA. There were no significant differences between mesenteric and omental or between deep and superficial abdominal subcutaneous adipose tissue. In protocol 2, meal fatty acid oxidation and uptake into subcutaneous and omental adipose tissue ([3H]triolein) were measured in six normal, healthy volunteers. Meal fatty acid oxidation (3H2O generation) plus that remaining in plasma ( approximately 1%) plus uptake into upper body subcutaneous, lower body subcutaneous, and visceral fat allowed us to account for 98 +/- 6% of meal fatty acids 24 h after meal ingestion. We conclude that omental fat is a good surrogate for visceral fat and that abdominal subcutaneous fat depots are comparable with regard to meal fatty acid metabolic studies. Using [3H]triolein, we were able to account for virtually 100% of meal fatty acids 24 h after meal ingestion. These results support the meal fatty acid tracer model as a way to study the metabolic fate of dietary fat.     

Insulin sensitivity and regional fat gain in response to overfeeding

Although insulin resistance and type 2 diabetes (T2DM) are associated with upper body fat distribution, it is unknown whether insulin resistance predisposes to upper body fat gain or whether upper body fat gain causes insulin resistance. Our objective was to determine whether insulin sensitivity predicts abdominal (subcutaneous and/or visceral) fat gain in normal weight adults. Twenty-eight (15 men) lean (BMI = 22.1 ± 2.5 kg/m(2)), healthy adults underwent ~8 weeks of overfeeding to gain ~4 kg fat. Body composition was assessed before and after overfeeding, using dual-energy X-ray absorptiometry (DXA) and abdominal computed tomography to measure total and regional (visceral, abdominal, and lower body subcutaneous) fat gain. We assessed insulin sensitivity with an intravenous glucose tolerance test (IVGTT) and the 24-h insulin area under the curve (AUC). We found a wide range of insulin sensitivity and a relatively narrow range of body fat distribution in this normal weight cohort. Participants gained 3.8 ± 1.7 kg of body fat (4.6 ± 2.2 kg body weight). The baseline 24-h AUC of insulin concentration was positively correlated with percent body fat (r = 0.43, P < 0.05). The contribution of leg fat gain to total fat gain ranged from 29 to 79%, whereas the contributions of abdominal subcutaneous fat and visceral fat gain to total fat gain ranged from 17 to 69% and -5 to 22%, respectively. Baseline insulin sensitivity, whether measured by an IVGTT (S(i)) or the 24-h AUC insulin, did not predict upper body subcutaneous or visceral fat gain in response to overfeeding. We conclude that reduced insulin sensitivity is not an obligate precursor to upper body fat gain.     

Sex‐ and Depot‐Dependent Differences in Adipogenesis in Normal‐Weight Humans

To elucidate cellular mechanisms of sex‐related differences in fat distribution, we determined body fat distribution (dual‐energy X‐ray absorptiometry and single‐slice abdominal computed tomography (CT)), adipocyte size, adipocyte number, and proportion of early‐differentiated adipocytes (aP2⁺CD68^?) in the stromovascular fraction (SVF) in the upper and lower body of normal‐weight healthy men (n = 12) and premenopausal women (n = 20) (age: 18–49 years, BMI: 18–26 kg/m²). Women had more subcutaneous and less visceral fat than men. The proportion of early differentiated adipocytes in the subcutaneous adipose tissue SVF of women was greater than in men (P = 0.01), especially in the femoral depot, although in vitro adipogenesis, as assessed by peroxisome proliferator activated receptor‐γ (PPARγ) expression, was not increased in femoral preadipocytes cultured from women compared with men. In women, differentiation of femoral preadipocytes was less than that of abdominal subcutaneous preadipocytes (P = 0.04), and femoral subcutaneous preadipocytes tended to be more resistant to tumor necrosis factor‐α (TNFα)–induced apoptosis (P = 0.06). Thus, turnover and utilization of the preadipocyte pool may be reduced in lower vs. the upper‐body fat in women. Collectively, these data indicate that the microenvironment, rather than differences in inherent properties of preadipocytes between genders, may explain the gynoid obesity phenotype and higher percent body fat in women compared to men.