Femoral Adipose Tissue Research Articles

Gluteal femoral subcutaneous and dermal adipose tissue in female.

During the sexual maturation, gluteal femoral adipose tissue is subjected to numerous modifications, not observable in other regions, in particular in women and less in men. Other authors described this region, but they used imaging techniques having lower resolution, than MRI proposed in this study. High resolution imaging techniques might provide important and more detailed information about the anatomy of gluteal femoral region. This study has been performed using 7 T-magnetic resonance imaging and ultrastructural analysis in order to provide accurate description of the subcutaneous adipose tissue and dermis of gluteal femoral region. In this study specimens harvested from cadavers and form living patients have been analyzed. The results showed the presence of three layers: superficial, middle, and deep, characterized by different organization of fat lobules. High resolution imaging showed the adipose papilla that originates from dermis and protrude in subcutaneous adipose tissue. Adipose papilla is characterized by a peculiar morphology with a basement, a neck and a head and these elements represent the functional subunits of adipose papilla. Moreover, ultrastructural study evidenced the relationship between adipocytes and sweat glands, regulated by lipid vesicles. This study provides important information about subcutaneous and dermal fat anatomy of gluteal femoral region, improving the past knowledge, and move toward a better understanding of the cellulite physiopathology.

The role of fetal adipose tissue thicknesses measured ultrasonographically in the prediction of gestational diabetes

AIM
 This study aims to investigate whether second-trimester fetal adipose tissue components reflect glycemic control in diabetic pregnancies and their role as an auxiliary method in predicting gestational diabetes.
 MATERIALS AND METHODS
 This study was designed prospectively, cross-sectionally in 300 pregnant women 24-28 weeks of gestation between April 2020 and July 2020. The adipose tissue thickness of the humerus, femur, scapula, and abdominal circumference was examined by transabdominal ultrasound. The age, body mass index, family history of diabetes, and diabetes history in previous pregnancies of the groups were questioned.
 RESULTS
 The anterior abdominal wall adipose tissue thickness of the fetuses we included in the study was 5 ± 0.8 mm, femur adipose tissue thickness was 4 ± 0.7 mm, humerus adipose tissue thickness was 3.7 ± 0.7 mm, scapula adipose tissue thickness was 4.1 ± 2,2 mm. The total adipose tissue thickness was 16.9 ± 2.9 mm.
 A statistically significant correlation was found between femoral adipose tissue thickness (p = 0.001) and humeral adipose tissue thickness (p = 0.023) in gestational diabetes groups.
 Patients with a diagnosis of Gestational Diabetes Mellitus (n = 60) constituted the first group, patients without GDM (n =240) constituted the second group. In our independent analysis of two groups, femur and humerus adipose tissue thickness were found to be statistically significantly different between both groups (p= 0.002, p = 0.043, respectively). Other parameters did not differ significantly between groups.
 Between three groups (healthy, impaired glucose tolerance, and gestational diabetes groups). Femoral adipose tissue thickness was statistically significant among the three groups (p = 0.005). As a result of binary logistic regression, if the femoral adipose tissue thickness was above 4.1 mm, the possibility of developing GDM was observed with 63.8% sensitivity and 65% specificity.
 CONCLUSION
 In the prediction of gestational diabetes, fetus femoral adipose tissue thickness may be significant

Effects of High-Intensity Exercise Training on Adipose Tissue Mass, Glucose Uptake and Protein Content in Pre- and Post-menopausal Women.

The menopausal transition is accompanied by changes in adipose tissue storage, leading to an android body composition associated with increased risk of type 2 diabetes and cardiovascular disease in post-menopausal women. Estrogens probably affect local adipose tissue depots differently. We investigated how menopausal status and exercise training influence adipose tissue mass, adipose tissue insulin sensitivity and adipose tissue proteins associated with lipogenesis/lipolysis and mitochondrial function. Healthy, normal-weight pre- (n = 21) and post-menopausal (n = 20) women participated in high-intensity exercise training three times per week for 12 weeks. Adipose tissue distribution was determined by dual-energy x-ray absorptiometry and magnetic resonance imaging. Adipose tissue glucose uptake was assessed by positron emission tomography/computed tomography (PET/CT) by the glucose analog [18F]fluorodeoxyglucose ([18F]FDG) during continuous insulin infusion (40 mU·m−2·min−1). Protein content associated with insulin signaling, lipogenesis/lipolysis, and mitochondrial function were determined by western blotting in abdominal and femoral white adipose tissue biopsies. The mean age difference between the pre- and the post-menopausal women was 4.5 years. Exercise training reduced subcutaneous (~4%) and visceral (~6%) adipose tissue masses similarly in pre- and post-menopausal women. Insulin-stimulated glucose uptake, assessed by [18F]FDG-uptake during PET/CT, was similar in pre- and post-menopausal women in abdominal, gluteal, and femoral adipose tissue depots, despite skeletal muscle insulin resistance in post- compared to pre-menopausal women in the same cohort. Insulin-stimulated glucose uptake in adipose tissue depots was not changed after 3 months of high-intensity exercise training, but insulin sensitivity was higher in visceral compared to subcutaneous adipose tissue depots (~139%). Post-menopausal women exhibited increased hexokinase and adipose triglyceride lipase content in subcutaneous abdominal adipose tissue. Physical activity in the early post-menopausal years reduces abdominal obesity, but insulin sensitivity of adipose tissue seems unaffected by both menopausal status and physical activity.

Lymphatic drainage affects lipolytic activity of femoral adipose tissue in women.

It has been shown that many molecules released by adipose tissue (AT) into interstitial fluid can reach the bloodstream preferentially via lymphatic system. Worsened lymphatic drainage may alter interstitial fluid (ISF) composition and thus affect microenvironment of adipocytes. Nevertheless, the effect of lymphatic drainage on AT functions remains unknown. Therefore, we analyzed the lipolytic activity of femoral AT in two groups of premenopausal women similar in adiposity but differing in the efficiency of lymphatic drainage of lower body as assessed by lymphoscintigraphy. Levels of lipolytic markers were assessed in plasma and ISF collected by skin blister technique in femoral area. In addition, microdialysis was used to monitor lipolysis of AT in vivo. Our results indicate that worsened lymphatic drainage is associated with lower in vivo lipolytic index and reduced lipolytic responsiveness of femoral AT to adrenergic stimuli. Thus, efficiency of lymphatic drainage appears to play a role in the regulation of AT metabolism. Accordingly, worsened lymphatic drainage could contribute to the resistance of lower body AT to intentional weigh loss.

Efficacy of Intermittent Compression Therapy versus Kinesio Tape on Cellulite in Females

AbstractBackground: Cellulite is defined as changes in the surface contour of the skin that result in orange peel or “mattress” appearance of the skin. Cellulite is not defined as a pathologic condition, but is a substantial cosmetic concern for many adult females.Aim of Study: To evaluate the efficacy of intermittent compression therapy versus Kinesio tape on cellulite in females.Subjects and Methods: They were selected from students of Faculty of Physical Therapy Cairo University since October till end of December 2018, thirty females with femoral adipose tissue cellulite grade ³1 according to Nurnberger-Muller scale at their thighs. Their ages ranged from 19-25 years and their body mass indices did not exceed 35kg/m2. They were divided randomly into two groups, Group (A) (kineso tape group): Was consisted of 15 females; they all received kinesio tape for 6 weeks in addition to low caloric diet (1200kcal/day) and condition related advices. Group (B) (intermittent compression therapy group): Was consisted of 15 females, they received intermittent compression therapy for 6 weeks in addition to low caloric diet (1200kcal/day) and condition related advices as in group (A) inclusion criteria thirty females suffering from grade ³1 cellulite according to Nurnberger-Muller scale with femoral adipose tissue, their ages ranged from 19-25 years, their body mass indices did not exceed 35kg/m2. Exclusion criteria history of uncontrolled hypertension, malignancy, mental disorders, diseases of skin (dermatological diseases), inflammation within treatment area and history of Deep Venous Thrombosis (DVT).Results: The percent decrease in the mean value of ultra-sound in both groups (A & B) were 4.81% and 14.36% respectively, the percent decrease in the mean value of round tape measurement in both groups A and B were 2.39% and 3.64% respectively and there was statistical significant decrease in the median value of photonumeric cellulite severity scale in group B [8.0 (4.50-11.)] when compared with its corres ponding value in group A [9.5 (6.0-12.0)] with Z-value=–2.124 and p-value=0.034.Conclusion: The results of this study showed that the use of KT and intermittent compression therapy resulted in sig-nificant reduction in femoral adipose tissue cellulite were observed favouring intermittent compression therapy approach.

A comparison between the abdominal and femoral adipose tissue proteome of overweight and obese women

Body fat distribution is an important determinant of cardiometabolic health. Lower-body adipose tissue (AT) has protective characteristics as compared to upper-body fat, but the underlying depot-differences remain to be elucidated. Here, we compared the proteome and morphology of abdominal and femoral AT. Paired biopsies from abdominal and femoral subcutaneous AT were taken from eight overweight/obese (BMI ≥ 28 kg/m2) women with impaired glucose metabolism after an overnight fast. Proteins were isolated and quantified using liquid chromatography-mass spectrometry, and protein expression in abdominal and femoral subcutaneous AT was compared. Moreover, correlations between fat cell size and the proteome of both AT depots were determined. In total, 651 proteins were identified, of which 22 proteins tended to be differentially expressed between abdominal and femoral AT after removal of blood protein signals (p < 0.05). Proteins involved in cell structure organization and energy metabolism were differently expressed between AT depots. Fat cell size, which was higher in femoral AT, was significantly correlated with ADH1B, POSTN and LCP1. These findings suggest that there are only slight differences in protein expression between abdominal and femoral subcutaneous AT. It remains to be determined whether these differences, as well as differences in protein activity, contribute to functional and/or morphological differences between these fat depots.

Differences in Upper and Lower Body Adipose Tissue Oxygen Tension Contribute to the Adipose Tissue Phenotype in Humans.

Upper and lower body adipose tissue (AT) exhibits opposing associations with obesity-related cardiometabolic diseases. Recent studies have suggested that altered AT oxygen tension (pO2) may contribute to AT dysfunction. Here, we compared in vivo abdominal (ABD) and femoral (FEM) subcutaneous AT pO2 in women who are overweight and have obesity, and investigated the effects of physiological AT pO2 on human adipocyte function. ABD and FEM subcutaneous AT pO2 and AT blood flow (ATBF) were assessed in eight [BMI (body mass index) 34.4 ± 1.6 kg/m2] postmenopausal women who were overweight with obesity and impaired glucose metabolism. ABD and FEM AT biopsy specimens were collected to determine adipocyte morphology and AT gene expression. Moreover, the effects of prolonged exposure (14 days) to physiological AT pO2 on adipokine expression/secretion, mitochondrial respiration, and glucose uptake were investigated in differentiated human multipotent adipose-derived stem cells. AT pO2 was higher in ABD than FEM AT (62.7 ± 6.6 vs 50.0 ± 4.5 mm Hg, P = 0.013), whereas ATBF was comparable between depots. Maximal uncoupled oxygen consumption rates were substantially lower in ABD than FEM adipocytes for all pO2 conditions. Low physiological pO2 (5% O2) decreased proinflammatory gene expression, increased basal glucose uptake, and altered adipokine secretion in ABD and FEM adipocytes. We demonstrated for the first time, to our knowledge, that AT pO2 is higher in ABD than FEM subcutaneous AT in women who are overweight/with obesity, partly due to a lower oxygen consumption rate in ABD adipocytes. Moreover, low physiological pO2 decreased proinflammatory gene expression and improved the metabolic phenotype in differentiated human adipocytes, whereas more heterogeneous effects on adipokine secretion were found.

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.

Acute Testosterone Deficiency Alters Adipose Tissue Fatty Acid Storage.

Although the long-term effects of testosterone on adipose tissue lipid metabolism in men have been defined, the short-term regulation of these effects is not well understood. We examined the effects of acute testosterone withdrawal on subcutaneous abdominal and femoral adipose tissue fatty acid (FA) storage and cellular mechanisms. This was a prospective, randomized trial. Mayo Clinic Clinical Research Unit. Thirty-two male volunteers ages 18 to 50 participated in these studies. Volunteers were randomized to receive (1) no treatment (control), (2) injections (7.5 mg) of Lupron®, or (3) Lupron and testosterone (L+T) replacement for 49 days, resulting in 4 weeks of sex steroid suppression in the Lupron group. We measured body composition, fat cell size, adipose tissue meal FA and direct free FA storage, lipoprotein lipase (LPL), acyl coenzyme A synthetase (ACS), diacylglycerol acyltransferase activities, and CD36 content. Compared with control and L+T groups, acute testosterone deficiency resulted in greater femoral adipose tissue meal FA storage rates, fasting and fed LPL activity, and ACS activity. These results suggest that in men, testosterone plays a tonic role in restraining FA storage in femoral adipose tissue via suppression of LPL and ACS activities. FA storage mechanisms in men appear sensitive to short-term changes in testosterone concentrations.

Acute Hypercortisolemia Exerts Depot-Specific Effects on Abdominal and Femoral Adipose Tissue Function.

Context:Glucocorticoids have pleiotropic metabolic functions, and acute glucocorticoid excess affects fatty acid metabolism, increasing systemic lipolysis. Whether glucocorticoids exert adipose tissue depot-specific effects remains unclear.Objective:To provide an in vivo assessment of femoral and abdominal adipose tissue responses to acute glucocorticoid administration.Design and Outcome Measures:Nine healthy male volunteers were studied on two occasions, after a hydrocortisone infusion (0.2 mg/kg/min for 14 hours) and a saline infusion, respectively, given in randomized double-blind order. The subjects were studied in the fasting state and after a 75-g glucose drink with an in vivo assessment of femoral adipose tissue blood flow (ATBF) using radioactive xenon washout and of lipolysis and glucose uptake using the arteriovenous difference technique. In a separate study (same infusion design), eight additional healthy male subjects underwent assessment of fasting abdominal ATBF and lipolysis only. Lipolysis was assessed as the net release of nonesterified fatty acids (NEFAs) from femoral and abdominal subcutaneous adipose tissue.Results:Acute hypercortisolemia significantly increased basal and postprandial ATBF in femoral adipose tissue, but the femoral net NEFA release did not change. In abdominal adipose tissue, hypercortisolemia induced substantial increases in basal ATBF and NEFA release.Conclusions:Acute hypercortisolemia induces differential lipolysis and ATBF responses in abdominal and femoral adipose tissue, suggesting depot-specific glucocorticoid effects. Abdominal, but not femoral, adipose tissue contributes to the hypercortisolemia-induced systemic NEFA increase, with likely contributions from other adipose tissue sources and intravascular triglyceride hydrolysis.

Cellular Mechanisms Driving Sex Differences in Adipose Tissue Biology and Body Shape in Humans and Mouse Models.

Sex differences in adipose tissue distribution and the metabolic, endocrine, and immune functions of different anatomical fat depots have been described, but they are incompletely documented in the literature. It is becoming increasingly clear that adipose depots serve distinct functions in males and females and have specific physiological roles. However, the mechanisms that regulate the size and function of specific adipose tissues in men and women remain poorly understood. New insights from mouse models have advanced our understanding of depot differences in adipose growth and remodeling via the proliferation and differentiation of adipose progenitors that can expand adipocyte number in the tissue or simply replace dysfunctional older and larger adipocytes. A limited ability of a depot to expand or remodel can lead to excessive adipocyte hypertrophy, which is often correlated with metabolic dysfunction. However, the relationship of adipocyte size and function varies by depot and sex. For example, femoral adipose tissues of premenopausal women appear to have a greater capacity for adipose expansion via hyperplasia and hypertrophy; although larger, these gluteal-femoral adipocytes remain insulin sensitive. The microenvironment of specific depots, including the composition of the extracellular matrix and cellular composition, as well as cell-autonomous genetic differences, influences sex- and depot-dependent metabolic and growth properties. Although there are some species differences, studies of the molecular and physiological determinants of sex differences in adipocyte growth and function in humans and rodents are both needed for understanding sex differences in health and disease.

Hypercortisolaemia increases femoral adipose tissue blood flow but not net fatty acid releasein vivo

Hypercortisolaemia increases femoral adipose tissue blood flow but not net fatty acid release<i>in vivo</i>

Effects of increased free fatty acid availability on adipose tissue fatty acid storage in men.

A portion of free fatty acids (FFA) released from adipose tissue lipolysis are re-stored in adipocytes via direct uptake. Rates of direct adipose tissue FFA storage are much greater in women than men, but women also have greater systemic FFA flux and more body fat. We tested the hypotheses that experimental increases in FFA in men would equalize the rates of direct adipose tissue FFA storage in men and women. We used a lipid emulsion infusion to raise FFA in men to levels seen in post-absorptive women. Direct FFA storage (μmol · kg fat(-1) · min(-1)) rates in abdominal and femoral fat was assessed using stable isotope tracer infusions to measure FFA disappearance rates and an iv FFA radiotracer bolus/timed biopsy. These studies were performed in a Clinical Research Center. Data from 13 non-obese women was compared with that from eight obese and eight non-obese men. The men received a lipid emulsion infusion to raise FFA. We measured the rates of direct FFA storage in abdominal and femoral adipose tissue. The three groups were similar in age and FFA flux by design; obese men had similar body fat percentage as non-obese women. Despite matching for FFA concentrations and flux, FFA storage per kg abdominal (P < .01) and femoral (P < .001) fat was less in both lean and obese men than in non-obese women. Abdominal FFA storage rates were correlated with proteins/enzymes in the FFA uptake/triglyceride synthesis pathway in men. The lesser rates of direct FFA adipose tissue in men compared with women cannot be explained by reduced FFA availability.

Abstract 17579: Quantification of Femoral Adipose Tissue Provides Novel Mechanistic Insights Into the "Obesity Paradox": a Translational Approach

Introduction: Obesity has been paradoxically associated with a better outcome of CAD patients, while anthropometic measures of obesity provide limited information on adipose tissue (AT) biology. We hypothesised that quantification of femoral AT (FemAT) deposition using U/S can provide mechanistic insights into the obesity paradox. Methods: FemAT biopsies from 185 pts undergoing coronary bypass surgery (CABG) were cultured ex vivo for secretome and gene expression studies. FemAT thickness was measured by U/S at both the anterior and exterior surface of the thigh, at the mid point of the distance between the iliac crest and the knee, and the average of both thighs was calculated. Malondialdehyde (MDA), a marker of oxidative stress, was measured in plasma and FemAT culture supernatants. Brachial artery (BA) flow mediated dilatation (FMD) and distensibility were assessed by U/S. Results: FemAT thickness was only weakly correlated with BMI (r=0.235, p&lt;0.001) and waist-to-hip ratio (WHR, r=-0.179, p&lt;0.05), suggesting that it provides different information to classic anthropometrics in obesity. Patients with increased FemAT thickness had lower plasma MDA (A), better FMD (B) and greater BA distensibility (C), despite of being more obese. On the contrary BMI did not predict systemic oxidative stress or vascular function, while WHR was weakly correlated only with FMD (rho=-0.156, p&lt;0.05). Increased FemAT thickness was associated with lower MDA release from FemAT culture supernatants (D), and lower IL6-receptor (E) / CD68 (F) expression in FemAT samples, suggesting lower endogenous oxidative stress, and less macrophages’ infiltration. Conclusions: Femoral fat accumulation is associated with lower local AT inflammation and favourable systemic effects on vascular function in CAD. Combining imaging with AT biology could help to better understand the role of obesity-related vascular disease and provide an explanation to the “obesity paradox”.

Adipose tissue lipolysis and circulating lipids in acute and subacute critical illness: Effects of shock and treatment

PurposeThe purpose of this study is to assess lipid metabolism at the tissue level in critically ill subjects. Materials and methodsWe studied 182 patients with systemic inflammatory response syndrome/severe sepsis or shock during the acute (day 1) and subacute phase of critical illness (day 6). All subjects had a tissue microdialysis (MD) catheter placed in femoral adipose tissue upon admission to the intensive care unit (ICU). Plasma cholesterol, high-density lipoprotein, low-density lipoprotein, free fatty acids (FFAs), triglyceride, and MD glycerol (GLYC) were measured on days 1 and 6 in the ICU. ResultsOn admission, 56% of the patients had increased levels (>200 μmol/L) of MD GLYC. Patients with shock displayed more pronounced subcutaneous tissue lipolysis and more profound derangements of circulating lipids vs patients without shock (but no appreciable differences in FFA levels). Furthermore, in patients with shock during the acute period, there were positive, albeit weak, correlations of subcutaneous tissue lipolysis (MD GLYC), plasma FFAs (r = 0.260; P = .01), and norepinephrine's dose (r = 0.230; P = .01), whereas during the subacute phase, MD GLY levels were higher in patients receiving glucocorticoids (344.7 ± 276.0 μmol/L vs 252.2 ± 158.4 μmol/L; P = .03). ConclusionsSubcutaneous tissue lipolysis is only one of the many determinants of plasma FFAs. Routinely applied therapeutic modalities in the ICU interfere with adipose tissue metabolism.

Depot-specific and sex-specific secretion of leptin and interleukin 6: higher leptin release in women and lower interleukin-6 release from femoral adipose tissue in vivo

BackgroundThe female fat distribution pattern of gluteofemoral fat mass accumulation is associated with protection from cardiovascular disease and diabetes. Furthermore, women are known to have higher systemic leptin concentrations than men. Differential adipokine secretion from subcutaneous adipose tissue depots may be responsible for these differences. We aimed to study the physiological release of leptin and interleukin (IL) 6, a pro-inflammatory adipokine, from abdominal and femoral adipose tissue in vivo. MethodsDepot-specific leptin and IL-6 release were measured in 42 healthy volunteers (23 men and 19 women), matched for age and body-mass index (mean 25·4 kg/m2). Measurements were carried out after an overnight fast. Leptin and IL-6 release were studied with the arteriovenous difference technique across abdominal and femoral adipose tissue. FindingsLeptin release showed a strong sex dichotomy with 3·5-fold higher systemic plasma concentrations (p<0·001) and a 3-fold higher leptin release rate per unit fat mass across abdominal and femoral adipose tissue in women than in men (p<0·05). In both men and women, abdominal and femoral leptin release were positively correlated with each other (r=0·54, p<0·001), and negatively correlated with waist-to-hip ratio (p<0·001, controlled for sex). Abdominal IL-6 release was higher than femoral IL-6 release (p=0·001), which was a consistent finding in both men and women. InterpretationAdipose tissue is characterised by differential adipokine secretion between sexes and subcutaneous fat depots. The widely observed higher systemic leptin concentration in women is a result of a high leptin production rate and large gluteofemoral fat mass compared with men. Femoral adipose tissue is characterised by a lower IL-6 release rate, which may suggest that gluteofemoral fat is resistant to low-grade inflammation. FundingHigher Education Funding Council for England.

ISP9: Not all fat is bad in cardiovascular risk. Mechanistic considerations about visceral versus femoral adipose tissues

ISP9: Not all fat is bad in cardiovascular risk. Mechanistic considerations about visceral versus femoral adipose tissues

Marked resistance of femoral adipose tissue blood flow and lipolysis to adrenaline in vivo

Fatty acid entrapment in femoral adipose tissue has been proposed to prevent ectopic fat deposition and visceral fat accumulation, resulting in protection from insulin resistance. Our objective was to test the hypothesis of femoral, compared with abdominal, adipose tissue resistance to adrenergic stimulation in vivo as a possible mechanism. Regional fatty acid trafficking, along with the measurement of adipose tissue blood flow (ATBF) with (133)Xe washout, was studied with the arteriovenous difference technique and stable isotope tracers in healthy volunteers. Adrenergic agonists (isoprenaline, adrenaline [epinephrine]) were infused either locally by microinfusion or systemically. Local microinfusion of adrenoceptor antagonists (propranolol, phentolamine) was used to characterise specific adrenoceptor subtype effects in vivo. Femoral adipose tissue NEFA release and ATBF were lower during adrenaline stimulation than in abdominal tissue (p < 0.001). Mechanistically, femoral adipose tissue displayed a dominant α-adrenergic response during adrenaline stimulation. The α-adrenoceptor blocker, phentolamine, resulted in the 'disinhibition' of the femoral ATBF response to adrenaline (p < 0.001). Fatty acids, once stored in femoral adipose tissue, are not readily released upon adrenergic stimulation. Femoral adipose tissue resistance to adrenaline may contribute to the prevention of ectopic fatty acid deposition.

Metabolic Alterations in Adipose Tissue During the Early Phase of Experimental Endotoxemia in Humans

Adipose tissue plays an important role in energy homeostasis; however, there is only little knowledge about its metabolic activity during critical illness or sepsis. We assessed adipose tissue metabolic activity and local blood flow during experimental endotoxemia in otherwise healthy humans. In a prospective, placebo controlled and randomized experiment we measured changes in lactate, glycerol, and pyruvate concentrations in microdialysate samples of femoral adipose tissue after an intravenous bolus of lipopolysaccharide (LPS, 4 ng/kg). Intravenous endotoxin caused an early and constant increase in interstitial pyruvate, while formation of lactate in adipose tissue was not affected. In contrast, lactate levels in serum were elevated significantly after 90 min (p<0.05) and likewise, serum glycerol concentrations rose 90 min after LPS treatment (p<0.05) and 60 min earlier than in adipose tissue. Subcutaneous adipose tissue blood perfusion increased 2-fold while there was a strong decline in skin blood flow. Pyruvate accumulation in subcutaneous adipose tissue is an early marker of endotoxemia. While adipose tissue is a major source of serum glycerol and lactate in humans during physiological conditions, it contributes only little to increased serum lactate and glycerol levels during endotoxemia.

Impact of Physical Inactivity on Adipose Tissue Low-Grade Inflammation in First-Degree Relatives of Type 2 Diabetic Patients

OBJECTIVEFirst-degree relatives (FDRs) of patients with type 2 diabetes may exhibit a disproportionately elevated risk of developing insulin resistance, obesity, and type 2 diabetes when exposed to physical inactivity, which to some unknown extent may involve low-grade inflammation. We investigated whether subjects who are nonobese FDRs show signs of low-grade inflammation before or after exposure to short-term physical inactivity.RESEARCH DESIGN AND METHODSWe studied 13 healthy FDR subjects and 20 control (CON) subjects matched for age, sex, and BMI before and after 10 days of bed rest (BR). Insulin sensitivity was measured by the hyperinsulinemic euglycemic clamp. Key low-grade inflammation mediators were measured in arterial blood and microdialysate from subcutaneous abdominal (SCAAT) and femoral adipose tissue. Adipokine mRNA expression was determined in SCAAT.RESULTSBefore BR, FDR subjects displayed insulin resistance, elevated plasma C-reactive protein, leptin, and monocyte chemoattractant protein (MCP)-1, high interleukin (IL)-6, and MCP-1 expressions, as well as low adiponectin and leptin expressions. FDR subjects responded to BR by decreasing plasma adiponectin and IL-10 expression and increasing plasma expression of IL-10 and tumor necrosis factor-α. In contrast, CON subjects responded to BR by increasing plasma adiponectin and adiponectin expression and by decreasing SCAAT microdialysate leptin.CONCLUSIONSYoung and nonobese FDR of patients with type 2 diabetes exhibit low-grade inflammation, which is further and disproportionately aggravated when exposed to physical inactivity. The study provides support for the notion that people at increased risk of type 2 diabetes should avoid even short periods of physical inactivity.