Subcutaneous Adipose Tissue Segmentation in Whole-Body MRI of Children

Obesity is associated mainly with adipose cell enlargement in adult man (hypertrophic obesity), whereas the formation of new fat cells (hyperplastic obesity) predominates in the prepubertal age. Adipose cell size, independent of body mass index, is negatively correlated with whole body insulin sensitivity. Here, we review recent findings linking hypertrophic obesity with inflammation and a dysregulated adipose tissue, including local cellular insulin resistance with reduced IRS-1 and GLUT4 protein content. In addition, the number of preadipocytes in the abdominal subcutaneous adipose tissue capable of undergoing differentiation to adipose cells is reduced in hypertrophic obesity. This is likely to promote ectopic lipid accumulation, a well-known finding in these individuals and one that promotes insulin resistance and cardiometabolic risk. We also review recent results showing that TNFα, but not MCP-1, resistin, or IL-6, completely prevents normal adipogenesis in preadipocytes, activates Wnt signaling, and induces a macrophage-like phenotype in the preadipocytes. In fact, activated preadipocytes, rather than macrophages, may completely account for the increased release of chemokines and cytokines by the adipose tissue in obesity. Understanding the molecular mechanisms for the impaired preadipocyte differentiation in the subcutaneous adipose tissue in hypertrophic obesity is a priority since it may lead to new ways of treating obesity and its associated metabolic complications.

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Thermogenic response to epinephrine in the forearm and abdominal subcutaneous adipose tissue

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1992.263.5.e850 ◽

1992 ◽

Vol 263 (5) ◽

pp. E850-E855 ◽

Cited By ~ 13

Author(s):

L. Simonsen ◽

J. Bulow ◽

J. Madsen ◽

N. J. Christensen

Keyword(s):

Skeletal Muscle ◽

Adipose Tissue ◽

Energy Expenditure ◽

Oxygen Uptake ◽

Glucose Uptake ◽

Subcutaneous Adipose Tissue ◽

Whole Body ◽

Epinephrine Infusion ◽

Basal Period ◽

Subcutaneous Adipose

Whole body energy expenditure, thermogenic and metabolic changes in the forearm, and intercellular glucose concentrations in subcutaneous adipose tissue on the abdomen determined by microdialysis were measured during epinephrine infusion in healthy subjects. After a control period, epinephrine was infused at rates of 0.2 and 0.4 nmol.kg-1 x min-1. Whole body resting energy expenditure was 4.36 +/- 0.56 (SD) kJ/min. Energy expenditure increased to 5.14 +/- 0.74 and 5.46 +/- 0.79 kJ/min, respectively (P < 0.001), during the epinephrine infusions. Respiratory exchange ratio was 0.80 +/- 0.04 in the resting state and did not change. Local forearm oxygen uptake was 3.9 +/- 1.3 mumol.100 g-1 x min-1 in the basal period. During epinephrine infusion, it increased to 5.8 +/- 2.1 (P < 0.03) and 7.5 +/- 2.3 mumol.100 g-1 x min-1 (P < 0.001). Local forearm glucose uptake was 0.160 +/- 0.105 mumol.100 g-1 x min-1 and increased to 0.586 +/- 0.445 and 0.760 +/- 0.534 mumol.100 g-1 x min-1 (P < 0.025). The intercellular glucose concentration in the subcutaneous adipose tissue on the abdomen was equal to the arterial concentration in the basal period but did not increase as much during infusion of epinephrine, indicating glucose uptake in adipose tissue in this condition. If it is assumed that forearm skeletal muscle is representative for the average skeletal muscle, it can be calculated that on average 40% of the enhanced whole body oxygen uptake induced by infusion of epinephrine is taking place in skeletal muscle. It is proposed that adipose tissue may contribute to epinephrine-induced thermogenesis.

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Production of glutamine and utilization of glutamate by rat subcutaneous adipose tissue in vivo

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1994.266.1.e151 ◽

1994 ◽

Vol 266 (1) ◽

pp. E151-E154 ◽

Cited By ~ 4

Author(s):

T. J. Kowalski ◽

M. Watford

Keyword(s):

Adipose Tissue ◽

Subcutaneous Adipose Tissue ◽

Sampling Technique ◽

Calibration Method ◽

Glutamine Metabolism ◽

Whole Body ◽

Arterial Blood ◽

Subcutaneous Adipose

Information about adipose tissue amino acid metabolism is limited, with most data derived from studies in vitro. The purpose of this study was to further characterize the role of adipose tissue in glutamine metabolism in the rat in vivo. The extracellular concentrations of glutamine, glutamate, alanine, and ammonia were measured in the rat inguinal fat pad using a microdialysis sampling technique. A calibration method was used to accurately assess the extracellular levels of metabolites, and a comparison of these concentrations with those in arterial blood allowed determination of the net flux of each compound. The adipose tissue-arterial blood concentration differences were 122 +/- 19, 54 +/- 37, -61 +/- 21, and -28 +/- 13 microM for glutamine, alanine, glutamate, and ammonia, respectively, indicating a production of glutamine and an uptake of glutamate by subcutaneous adipose tissue. The magnitude of glutamine production suggests that adipose tissue may play a significant role in whole body glutamine homeostasis.

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Estradiol acutely inhibits whole body lipid oxidation and attenuates lipolysis in subcutaneous adipose tissue: a randomized, placebo-controlled study in postmenopausal women

Acta Endocrinologica ◽

10.1530/eje-12-0422 ◽

2012 ◽

Vol 167 (4) ◽

pp. 543-551 ◽

Cited By ~ 14

Author(s):

Lars Christian Gormsen ◽

Christian Høst ◽

Britta Eilersen Hjerrild ◽

Steen Bønløkke Pedersen ◽

Søren Nielsen ◽

...

Keyword(s):

Adipose Tissue ◽

Lipid Oxidation ◽

Postmenopausal Women ◽

Adrenergic Receptor ◽

Subcutaneous Adipose Tissue ◽

Vascular Reactivity ◽

Whole Body ◽

Body Lipid ◽

Receptor Mrna ◽

Subcutaneous Adipose

ContextEstradiol (E2) promotes and maintains the female phenotype characterized by subcutaneous fat accumulation. There is evidence to suggest that this effect is due to increased anti-lipolytic α2A-adrenergic receptors, but whether this requires long-term exposure to E2or is an immediate effect is not clear.ObjectiveTo study acute effects of a single dose (4 mg) of 17β-E2on regional and systemic lipolysis.MethodsSixteen postmenopausal women (age, 59±5 years; weight, 67±10 kg; and BMI, 24.8±2.9) were studied in a crossover design: i) placebo and ii) 4 mg E2. Basal and adrenaline-stimulated regional lipolysis was assessed by microdialysis and substrate oxidation rates by indirect calorimetry. Tissue biopsies were obtained to assess lipoprotein lipase activity and mRNA expression of adrenergic, estrogen, cytokine, and vascular reactivity receptors.ResultsAcute E2stimulation significantly attenuated catecholamine-stimulated lipolysis in femoral subcutaneous adipose tissue (interstitial glycerol concentration (micromole/liter) ANOVA time vs treatment interaction,P=0.01) and lipolysis in general in abdominal adipose tissue (ANOVA treatment alone,P<0.05). E2also reduced basal lipid oxidation ((mg/kg per min) placebo, 0.58±0.06 vs E2, 0.45±0.03;P=0.03) and induced a significantly higher expression of anti-lipolytic α2A-adrenergic receptor mRNA (P=0.02) in skeletal muscle tissue as well as an upregulation ofeNOS(NOS3) mRNA (P=0.02).ConclusionE2acutely attenuates the lipolytic response to catecholamines in subcutaneous adipose tissue, shifts muscular adrenergic receptor mRNA toward anti-lipolytic α2A-receptors, decreases whole body lipid oxidation, and enhances expression of markers of vascular reactivity.

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Subcutaneous adipose tissue zinc-α2-glycoprotein is associated with adipose tissue and whole-body insulin sensitivity

Obesity ◽

10.1002/oby.20764 ◽

2014 ◽

Vol 22 (8) ◽

pp. 1821-1829 ◽

Cited By ~ 30

Author(s):

Miroslav Balaz ◽

Marek Vician ◽

Zuzana Janakova ◽

Timea Kurdiova ◽

Martina Surova ◽

...

Keyword(s):

Adipose Tissue ◽

Insulin Sensitivity ◽

Subcutaneous Adipose Tissue ◽

Whole Body ◽

Subcutaneous Adipose

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Macrophage Content in Subcutaneous Adipose Tissue: Associations With Adiposity, Age, Inflammatory Markers, and Whole-Body Insulin Action in Healthy Pima Indians

Diabetes ◽

10.2337/db08-0536 ◽

2008 ◽

Vol 58 (2) ◽

pp. 385-393 ◽

Cited By ~ 81

Author(s):

E. Ortega Martinez de Victoria ◽

X. Xu ◽

J. Koska ◽

A. M. Francisco ◽

M. Scalise ◽

...

Keyword(s):

Adipose Tissue ◽

Subcutaneous Adipose Tissue ◽

Inflammatory Markers ◽

Insulin Action ◽

Whole Body ◽

Pima Indians ◽

Subcutaneous Adipose

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Aerobic exercise elevates markers of angiogenesis and macrophage IL-6 gene expression in the subcutaneous adipose tissue of overweight-to-obese adults

Journal of Applied Physiology ◽

10.1152/japplphysiol.00614.2017 ◽

2017 ◽

Vol 123 (5) ◽

pp. 1150-1159 ◽

Cited By ~ 15

Author(s):

Douglas W. Van Pelt ◽

Lisa M. Guth ◽

Jeffrey F. Horowitz

Keyword(s):

Adipose Tissue ◽

Aerobic Exercise ◽

Mrna Expression ◽

Subcutaneous Adipose Tissue ◽

Acute Exercise ◽

Whole Body ◽

Exercise Session ◽

Obese Adults ◽

Important Regulator ◽

Subcutaneous Adipose

Alterations in the inflammatory state, metabolic function, and structure of subcutaneous adipose tissue (SAT) can impact the development of insulin resistance in obesity. Exercise can improve metabolic health in obesity, but the effects of exercise on SAT are not well known. The purpose of this study was to examine the effects of acute exercise and habitual exercise training on mRNA expression of markers of lipid metabolism, inflammation, fibrosis, and hypoxia/angiogenesis in SAT, as well as adipocyte cell size. We recruited overweight-to-obese adults who exercised regularly (ACTIVE: n = 8) or were sedentary (SED: n = 12). The groups were well matched for age (27 ± 1 vs. 24 ± 2 yr), body mass index (29 ± 1 vs. 27 ± 1 kg/m2), and body composition (30 ± 1 vs. 29 ± 1% body fat), but as expected, cardiorespiratory fitness was greater in ACTIVE vs. SED (V̇o2peak: 51 ± 3 vs. 42 ± 1 ml·kg fat-free mass−1·min−1; P = 0.01). Abdominal SAT biopsy samples were obtained before and 1 h after a single session of aerobic exercise (60 min at ~65% V̇o2peak). The exercise session increased SAT mRNA expression of VEGFA, an important regulator of angiogenic processes, in both groups. In addition, SAT from ACTIVE subjects had greater mRNA expression of the endothelial cell marker CD31 compared with SED, which may be a cumulative effect of the transient increases in VEGFA with regular exercise. We also magnetically sorted CD14+ immune cells from SAT samples and found that IL-6 expression was elevated in ACTIVE compared with SED. In conclusion, exercise initiates increases in factors related to angiogenic processes and may promote alterations in macrophage inflammation in SAT. NEW & NOTEWORTHY Acute exercise in overweight/obese adults increased subcutaneous adipose tissue (SAT) mRNA expression of VEGFA, an important regulator of angiogenesis and capillary growth. In addition, subjects that regularly exercise had elevated SAT CD31 mRNA expression and elevated IL-6 mRNA in adipose tissue macrophages compared with nonexercisers. This study demonstrates that aerobic exercise may alter processes related to whole body metabolic outcomes in obesity, such as angiogenesis and immune response, in the SAT of overweight/obese adults.

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Effect of training on insulin sensitivity of glucose uptake and lipolysis in human adipose tissue

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.2000.279.2.e376 ◽

2000 ◽

Vol 279 (2) ◽

pp. E376-E385 ◽

Cited By ~ 55

Author(s):

Bente Stallknecht ◽

Jens J. Larsen ◽

Kari J. Mikines ◽

Lene Simonsen ◽

Jens Bülow ◽

...

Keyword(s):

Blood Flow ◽

Adipose Tissue ◽

Insulin Sensitivity ◽

Glucose Uptake ◽

Subcutaneous Adipose Tissue ◽

Whole Body ◽

Tissue Blood Flow ◽

Glycerol Concentration ◽

Adipose Tissue Blood Flow ◽

Subcutaneous Adipose

Training increases insulin sensitivity of both whole body and muscle in humans. To investigate whether training also increases insulin sensitivity of adipose tissue, we performed a three-step hyperinsulinemic, euglycemic clamp in eight endurance-trained (T) and eight sedentary (S) young men [insulin infusion rates: 10,000 ( step I), 20,000 ( step II), and 150,000 ( step III) μU · min−1 · m−2]. Glucose and glycerol concentrations were measured in arterial blood and also by microdialysis in interstitial fluid in periumbilical, subcutaneous adipose tissue and in quadriceps femoris muscle (glucose only). Adipose tissue blood flow was measured by 133Xe washout. In the basal state, adipose tissue blood flow tended to be higher in T compared with S subjects, and in both groups blood flow was constant during the clamp. The change from basal in arterial-interstitial glucose concentration difference was increased in T during the clamp but not in S subjects in both adipose tissue and muscle [adipose tissue: step I ( n = 8), 0.48 ± 0.18 mM (T), 0.23 ± 0.11 mM (S); step II ( n = 8), 0.19 ± 0.09 (T), −0.09 ± 0.24 (S); step III( n = 5), 0.47 ± 0.24 (T), 0.06 ± 0.28 (S); (T: P < 0.001, S: P > 0.05); muscle: step I ( n = 4), 1.40 ± 0.46 (T), 0.31 ± 0.21 (S); step II ( n = 4), 1.14 ± 0.54 (T), −0.08 ± 0.14 (S); step III( n = 4), 1.23 ± 0.34 (T), 0.24 ± 0.09 (S); (T: P < 0.01, S: P > 0.05)]. Interstitial glycerol concentration decreased faster in T than in S subjects [half-time: T, 44 ± 9 min ( n = 7); S, 102 ± 23 min ( n = 5); P < 0.05]. In conclusion, training enhances insulin sensitivity of glucose uptake in subcutaneous adipose tissue and in skeletal muscle. Furthermore, interstitial glycerol data suggest that training also increases insulin sensitivity of lipolysis in subcutaneous adipose tissue. Insulin per se does not influence subcutaneous adipose tissue blood flow.

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Whole body and abdominal lipolytic sensitivity to epinephrine is suppressed in upper body obese women

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.2000.278.6.e1144 ◽

2000 ◽

Vol 278 (6) ◽

pp. E1144-E1152 ◽

Cited By ~ 74

Author(s):

Jeffrey F. Horowitz ◽

Samuel Klein

Keyword(s):

Adipose Tissue ◽

Subcutaneous Adipose Tissue ◽

Lipolytic Activity ◽

Fat Free Mass ◽

Upper Body ◽

Whole Body ◽

Tissue Blood Flow ◽

Obese Women ◽

Epinephrine Infusion ◽

Subcutaneous Adipose

We measured whole body and regional lipolytic and adipose tissue blood flow (ATBF) sensitivity to epinephrine in 8 lean [body mass index (BMI): 21 ± 1 kg/m2] and 10 upper body obese (UBO) women (BMI: 38 ± 1 kg/m2; waist circumference >100 cm). All subjects underwent a four-stage epinephrine infusion (0.00125, 0.005, 0.0125, and 0.025 μg ⋅ kg fat-free mass−1 ⋅ min−1) plus pancreatic hormonal clamp. Whole body free fatty acid (FFA) and glycerol rates of appearance (Ra) in plasma were determined by stable isotope tracer methodology. Abdominal and femoral subcutaneous adipose tissue lipolytic activity was determined by microdialysis and 133Xe clearance methods. Basal whole body FFA Ra and glycerol Ra were both greater ( P < 0.05) in obese (449 ± 31 and 220 ± 12 μmol/min, respectively) compared with lean subjects (323 ± 44 and 167 ± 21 μmol/min, respectively). Epinephrine infusion significantly increased FFA Ra and glycerol Ra in lean (71 ± 21 and 122 ± 52%, respectively; P < 0.05) but not obese subjects (7 ± 6 and 39 ± 10%, respectively; P = not significant). In addition, lipolytic and ATBF sensitivity to epinephrine was blunted in abdominal but not femoral subcutaneous adipose tissue of obese compared with lean subjects. We conclude that whole body lipolytic sensitivity to epinephrine is blunted in women with UBO because of decreased sensitivity in upper body but not lower body subcutaneous adipose tissue.

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