Femoral Depots Research Articles

From an Apple to a Pear: Moving Fat around for Reversing Insulin Resistance.

Type 2 diabetes (T2D) is a chronic condition where the body is resistant to insulin, leading to an elevated blood glucose state. Obesity is a main factor leading to T2D. Many clinical studies, however, have described a proportion of obese individuals who express a metabolically healthy profile, whereas some lean individuals could develop metabolic disorders. To study obesity as a risk factor, body fat distribution needs to be considered rather than crude body weight. Different individuals' bodies favor storing fat in different depots; some tend to accumulate more fat in the visceral depot, while others tend to store it in the femoral depot. This tendency relies on different factors, including genetic background and lifestyle. Consuming some types of medications can cause a shift in this tendency, leading to fat redistribution. Fat distribution plays an important role in the progression of risk of insulin resistance (IR). Apple-shaped individuals with enhanced abdominal obesity have a higher risk of IR compared to BMI-matched pear-shaped individuals, who store their fat in the gluteal-femoral depots. This is related to the different adipose tissue physiology between these two depots. In this review, we will summarize the recent evidence highlighting the underlying protective mechanisms in gluteal-femoral subcutaneous adipose tissues compared to those associated with abdominal adipose tissue, and we will revise the recent evidence showing antidiabetic drugs that impact fat distribution as they manage the T2D condition.

2032-P: Adipose Tissue Inflammation after Weight Loss

Background: Studies of changes in adipose tissue (AT) inflammation after weight loss have conflicting results. Our aim was to evaluate the changes in AT macrophages, senescence and AT insulin resistance after weight loss. Methods: Twenty-five participants (18 women) with obesity underwent a lifestyle intervention weight loss program and abdominal-femoral AT biopsies. AT insulin resistance was estimated calculating the insulin concentration that suppresses lipolysis by 50% (IC50) during a hyperinsulinemic-euglycemic clamp. Immunohistochemistry was used to estimate total adipose tissue macrophage (ATM) content (CD68+), pro-inflammatory ATM (CD14+), anti-inflammatory ATM (CD206+). Senescent cells in AT were identified by senescence associated β-galactosidase staining. All parameters were assessed before and after weight loss. Results: Median BMI was 34 kg/m2 (IQR, 32-35). A median percent weight loss of 10.2% (IQR, 6.5-12.1) resulted in a mean IC50 reduction of -6.2 ± 13 µIU/mL, p=0.03. There was no significant change in ATM content in the abdominal or femoral fat depots after weight loss, except for an increase in CD68 ATMs (mean change 4.5 ± 7.1 ATM/100 adipocytes, P=0.02) in the femoral depot. The proportion of senescent pre-adipocytes in abdominal and femoral depots remained unchanged after weight loss. In the abdominal depot, there was no relationship between IC 50 and CD68 or CD206 ATMs after weight loss, R2= 0.11, P=0.15 and R2= 0.08, P =0.22, for CD68 and CD206 ATMs respectively. There was a weak negative relationship between CD14 ATMs and IC 50 (R2=0.2, P =0.04). In the femoral depot, there was a weak negative relationship between IC 50 and CD68 ATMs (R2=0.23, P=0.04), and no relationship between IC 50 and CD14 ATMs (R2= 0.2, P=0.06) or CD206 ATMs after weight loss (R2= 0.06, P=0.33). Conclusion: Moderate weight loss is not associated with reduction in ATM content or senescent pre-adipocytes, despite an improvement in AT insulin resistance. Our results suggest that recruitment of some populations of ATMs increases after weight loss. Disclosure A.E. Espinosa De Ycaza: None. E. Søndergaard: None. M. Morgan-Bathke: None. D.A. Delivanis: None. B.G. Carranza Leon: None. K. Lytle: None. M.D. Jensen: None.

Effects of short-term sex steroid suppression on dietary fat storage patterns in healthy males.

Hypogonadism in males is associated with increased body fat and altered postprandial metabolism, but mechanisms remain poorly understood. Using a cross‐over study design, we investigated the effects of short‐term sex hormone suppression with or without testosterone add‐back on postprandial metabolism and the fate of dietary fat. Eleven healthy males (age: 29 ± 4.5 year; BMI: 26.3 ± 2.1 kg/m2) completed two 7‐day study phases during which hormone levels were altered pharmacologically to produce a low sex hormone condition (gonadotropin releasing hormone antagonist, aromatase inhibitor, and placebo gel) or a testosterone add‐back condition (testosterone gel). Following 7 days of therapy, subjects were administered an inpatient test meal containing 50 μCi of [1‐14C] oleic acid. Plasma samples were collected hourly for 5 h to assess postprandial responses. Energy metabolism (indirect calorimetry) and dietary fat oxidation (14CO2 in breath) were assessed at 1, 3, 5, 13.5, and 24 h following the test meal. Abdominal and femoral adipose biopsies were taken 24 h after the test meal to determine uptake of the labeled lipid. Postprandial glucose, insulin, free‐fatty acid, and triglyceride responses were not different between conditions (P > 0.05). Whole‐body energy metabolism was also not different between conditions at any time point (P > 0.05). Dietary fat oxidation trended lower (P = 0.12) and the relative uptake of 14C labeled lipid into femoral adipose tissue was greater (P = 0.03) in the low hormone condition. Short‐term hormone suppression did not affect energy expenditure or postprandial metabolism, but contributed to greater relative storage of dietary fat in the femoral depot. ClinicalTrials.gov Identifier: NCT03289559.

Adipocyte Fatty Acid Storage Factors Enhance Subcutaneous Fat Storage in Postmenopausal Women

Increases in weight have been associated with corresponding increases in insulin resistance in postmenopausal women. Although estrogen has significant impact on body fat and body fat distribution, the cellular mechanisms that influence this process are not yet known. We measured adipose tissue fatty acid (FA) storage and FA storage factors in 12 premenopausal and 11 postmenopausal women matched for age and body composition. Postmenopausal women had lower postprandial FA oxidation (indirect calorimetry), greater meal FA, and direct free FA (FFA) storage than premenopausal women, including two-fold greater meal FA storage in the femoral depot. The fed/fasted activities of adipose tissue lipoprotein lipase were not significantly different between premenopausal and postmenopausal women. In contrast, adipocyte acyl-CoA synthetase and diacylglycerol acyltransferase activities in postmenopausal women were significantly upregulated and were positively correlated with direct FFA storage rates. These findings suggest that the propensity for subcutaneous adipose tissue FA storage is increased in postmenopausal women, more so from changes in adipocyte FA storage factors than from adipose tissue lipoprotein lipase activity. Our results suggest that female sex steroids, most likely estrogen, have important effects on adipose tissue FA storage and FA oxidation that could promote fat gain in postmenopausal women.

Weight loss and regain in obese individuals: a link with adipose tissue metabolism indices?

This study was performed to examine whether changes in subcutaneous adipose tissue (SCAT) metabolism indices after weight loss were related to the magnitude of weight regain. Nine men and ten premenopausal women whose body mass index ranged from 30 to 42 kg/m(2), 35-48 years old, were studied before and after a 15-week weight loss program, as well as at a 17-22-month follow-up period. Although body composition was evaluated at all study periods, abdominal and femoral SCAT-lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) activities, and α2- and β-adrenoceptors (ARs) were measured before and after weight loss, exclusively. Although the SCAT-LPL activity did not change after weight loss in men, it tended to decrease in the femoral depot of women (p = 0.06). SCAT-HSL activity remained unchanged after weight reduction in men, while the post-weight loss lipase activity tended to be higher in both regions of women (p = 0.06). Although the post-weight loss number of β-ARs was higher irrespective of the fat depot (0.001 < p < 0.05), the number of α2-ARs was increased in the femoral (p < 0.05), but not in the abdominal SCAT (p = 0.08) after weight reduction, in men. Neither the α2- nor the β-AR density changed after weight reduction, in women. Abdominal SCAT-LPL activity after weight reduction was negatively related to weight regain indices, in women (-0.65 < Rhô < -0.75; 0.01 < p < 0.05). Both the post-weight loss abdominal SCAT α2-AR density and the α2-/β-AR balance were positively associated with weight regain indices, in men (0.69 < Rhô < 0.88; 0.01 < p < 0.05). These results suggest that selected SCAT metabolism indices could predict failure to weight loss maintenance, in both genders.

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: 18-26kg/m(2)). 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.

Impact of Walking on Adipose Tissue Lipoprotein Lipase Activity and Expression in Pre- and Postmenopausal Women

Objective: The aim of this study was to examine regional variation in adipose tissue lipoprotein lipase (AT-LPL) activity and expression in pre-and postmenopausal women, before and after training, once differences in chronological age or obesity degree are taken into account. Methods: Sixteen late pre- and 14 early postmenopausal (49 ± 2 vs. 52 ± 2 years; p < 0.001) moderately obese women (body mass index 29–35 kg/m²) were subjected to a 16-week walking program (3 sessions/week of 45 min at 60% heart rate reserve). Abdominal and femoral AT-LPL activity and expression, fasting lipidlipoprotein profile, body composition, and cardiorespiratory fitness (CRF) were measured before and after our intervention. Statistical analyses were performed using covariance analysis for age differences. Results: AT-LPL activity and expression, lipid-lipoprotein metabolism, body fatness, and CRF were similar at baseline, irrespective of the group considered. Slight reductions in plasma cholesterol and high-density lipoprotein (HDL) cholesterol levels, fat mass and waist girth reductions, CRF increases as well as femoral AT-LPL activity and expression decreases after our intervention were comparable, regardless of menopausal status (0.0001 < p < 0.05). Conclusions: Lipid storage is decreased in the femoral depot after walking, regardless of menopausal status. Reduction in AT-LPL activity or expression does not lead to a more deleterious lipid-lipoprotein profile, despite the modest decrease noted in HDL cholesterol concentrations.

Regional adipocyte precursors in the female rat. Influence of ovarian factors.

A flow cytometric immunofluorescence procedure utilizing a specific antibody to rat adipose tissue lipoprotein lipase (LPL) was developed to quantify differentiated and undifferentiated preadipocytes present in the adipose tissue vascular stroma. This method is highly sensitive and specific for cells capable of synthesizing LPL in significant quantities. Pubescence in female rats was associated with an increase in differentiated preadipocytes and in fat cell number with enlargement of the fat depots in the perirenal, parametrial, and the subcutaneous dorsal and femoral regions. A concomitant decline in the percentage of undifferentiated preadipocytes occurred in all but the femoral depot. Ovariectomy reduced pubertal adipose growth in the femoral and parametrial but not the dorsal or perirenal regions. Furthermore, the femoral undifferentiated preadipocyte pool was not preserved in the ovariectomized animals. Thus, ovarian factors influence the pubescence-associated regional preadipocyte differentiation and conversion to adipocytes. The femoral depot contains an ovarian-dependent infinite pool of fat cell precursors. These features could account for the association between ovarian hormones and body fat topography.

Fat cell metabolism in different regions in women. Effect of menstrual cycle, pregnancy, and lactation.

Adipose tissue lipolysis and lipoprotein lipase (LPL) activity were studied in biopsies from the femoral and abdominal depots in healthy women during early or late menstrual cycle, pregnancy, and the lactation period. When the differences in cell size were taken into account, basal lipolysis was similar in both regions in nonpregnant women. During lactation, however, lipolysis was significantly higher in the femoral region. The lipolytic effect of noradrenaline (10(-6) M) was significantly less in the femoral region in the nonpregnant women and during early pregnancy. However, the lipolytic response was the same in both regions in lactating women. LPL activity was higher in the femoral than in the abdominal region except during lactation when a marked decrease in the LPL activity was seen in the femoral region. The LPL activity in the abdominal region remained unchanged in all patient groups. The results imply that in both nonpregnant and pregnant women lipid assimilation is favored in the femoral depot. During lactation, however, the metabolic pattern changes; the LPL activity decreases and lipid mobilization increases in this depot. These changes are much less pronounced in the abdominal region. Thus, fat cells from different regions show a differential response during pregnancy and lactation. These results suggest that the adipose tissue in different regions may have specialized functions.