Deep subcutaneous adipose tissue: a distinct abdominal adipose depot

Objective: Abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) display significant metabolic differences, with VAT showing a functional association to metabolic/cardiovascular disorders. A third abdominal adipose layer, derived by the division of SAT and identified as deep subcutaneous adipose tissue (dSAT), may play a significant and independent metabolic role. The aim of this study was to evaluate depot‐specific differences in the expression of proteins key to adipocyte metabolism in a lean population to establish a potential physiologic role for dSAT. Research Methods and Procedures: Adipocytes and preadipocytes were isolated from whole biopsies taken from superficial SAT (sSAT), dSAT, and VAT samples obtained from 10 healthy normal weight patients (7 women and 3 men), with a mean age of 56.4 ± 4.04 years and a mean BMI of 23.1 ± 0.5 kg/m². Samples were evaluated for depot‐specific differences in insulin sensitivity using adiponectin, glucose transport protein 4 (GLUT4), and resistin mRNA and protein expression, glucocorticoid metabolism by 11β‐hydroxysteroid dehydrogenase type‐1 (11β‐HSD1) expression, and alterations in the adipokines leptin and tumor necrosis factor‐α (TNF‐α). Results: Although no regional differences in expression were observed for adiponectin or TNF‐α, dSAT whole biopsies and adipocytes, while intermediary to both sSAT and VAT, reflected more of the VAT expression profile of 11β‐HSD1, leptin, and resistin. Only in the case of the intracellular pool of GLUT4 proteins in whole biopsies was an independent pattern of expression observed for dSAT. In an evaluation of the homeostatic model, dSAT 11β‐HSD1 protein (r = 0.9573, p = 0.0002) and TNF‐α mRNA (r = 0.8210, p = 0.0236) correlated positively to the homeostatic model. Discussion: Overall, dSAT seems to be a distinct abdominal adipose depot supporting an independent metabolic function that may have a potential role in the development of obesity‐associated complications.     

Subdivisions of subcutaneous abdominal adipose tissue and insulin resistance

Whereas truncal (central) adiposity is strongly associated with the insulin resistant metabolic syndrome, it is uncertain whether this is accounted for principally by visceral adiposity (VAT). Several recent studies find as strong or stronger association between subcutaneous abdominal adiposity (SAT) and insulin resistance. To reexamine the issue of truncal adipose tissue depots, we performed cross-sectional abdominal computed tomography, and we undertook the novel approach of partitioning SAT into the plane superficial to the fascia within subcutaneous adipose tissue (superficial SAT) and that below this fascia (deep SAT), as well as measurement of VAT. Among 47 lean and obese glucose-tolerant men and women, insulin-stimulated glucose utilization, measured by euglycemic clamp, was strongly correlated with both VAT and deep SAT (r = -0.61 and -0.64, respectively; both P < 0.001), but not with superficial SAT (r = -0.29, not significant). Also, VAT and deep SAT followed a highly congruent pattern of associations with glucose and insulin area under the curve (75-g oral glucose tolerance test), mean arterial blood pressure, apoprotein-B, high-density lipoprotein cholesterol, and triglyceride. Superficial SAT had markedly weaker association with all these parameters and instead followed the pattern observed for thigh subcutaneous adiposity. We conclude that there are two functionally distinct compartments of adipose tissue within abdominal subcutaneous fat and that the deep SAT has a strong relation to insulin resistance.     

In vivo human lipolytic activity in preperitoneal and subdivisions of subcutaneous abdominal adipose tissue

We studied eight normal-weight male subjects to examine whether the lipolytic rate of deep subcutaneous and preperitoneal adipose tissues differs from that of superficial abdominal subcutaneous adipose tissue. The lipolytic rates in the superficial anterior and deep posterior subcutaneous abdominal adipose tissues and in the preperitoneal adipose tissue in the round ligament were measured by microdialysis and (133)Xe washout under basal, postabsorptive conditions and during intravenous epinephrine infusion (0.15 nmol. kg(-1). min(-1)). Both in the basal state and during epinephrine stimulation, the superficial subcutaneous adipose tissue had higher interstitial glycerol concentrations than the two other depots. Similarly, the calculated glycerol outputs from the superficial depot were significantly higher than those from the deep subcutaneous and the preperitoneal depots. Thus, it is concluded that the lipolytic rate of the superficial subcutaneous adipose tissue on the anterior abdominal wall is higher than that of the deep subcutaneous adipose tissue on the posterior abdominal wall and that of the preperitoneal adipose tissue in the round ligament.     

Lack of antilipolytic effect of lactate in subcutaneous abdominal adipose tissue during exercise.

The purpose of our study was to evaluate the potential inhibition of adipose tissue mobilization by lactate. Eight male subjects (age, 26. 25 +/- 1.75 yr) in good physical condition (maximal oxygen uptake, 59.87 +/- 2.77 ml. kg-1. min-1; %body fat, 10.15 +/- 0.89%) participated in this study. For each subject, two microdialysis probes were inserted into abdominal subcutaneous tissue. Lactate (16 mM) was perfused via one of the probes while physiological saline only was perfused via the other, both at a flow rate of 2.5 microl/min. In both probes, ethanol was also perfused for adipose tissue blood flow estimation. Dialysates were collected every 10 min during rest (30 min), exercise at 50% maximal oxygen consumption (120 min), and recovery (30 min) for the measurement of glycerol concentration. During exercise, glycerol increased significantly in both probes. However, no differences in glycerol level and ethanol extraction were observed between the lactate and control probes. These findings suggest that lactate does not impair subcutaneous abdominal adipose tissue mobilization during exercise.     

Expression of lipoprotein lipase in different human subcutaneous adipose tissue regions

Steady state expression of lipoprotein lipase was compared in abdominal and gluteal subcutaneous adipose tissue of nonobese men and women. In both regions enzyme activity and lipoprotein lipase mRNA levels were significantly higher in women than in men. In men the enzyme activity was higher in abdominal than in gluteal adipose tissue (P less than 0.01) whereas the opposite was observed in women (P less than 0.05). In both sexes, however, lipoprotein lipase mRNA levels were threefold higher in the abdominal as compared to the gluteal site, whether they were determined in isolated fat cells or in fat segments (P less than 0.01). This regional difference persisted when the mRNA values were expressed as a function of the mRNA concentration for beta-actin. There was a correlation between the two adipose tissue regions as regards the values for enzyme activity and mRNA level (r = 0.6-0.8). Northern blot analysis revealed two mRNA species of 3.5 and 3.7 kilobases, respectively. It is concluded that there are regional variations in the steady state expression of lipoprotein lipase in human subcutaneous adipose tissue. This involves site variations in gene expression as well as posttranslational modification of lipoprotein lipase enzyme activity and may contribute to the characteristic variations in adipose tissue mass and distribution between men and women.     

In vitro metabolism of cortisol by human abdominal adipose tissue

[1,2-3H]-cortisol was incubated with homogenates of abdominal subcutaneous adipose tissue obtained from non-obese and obese female patients. In the presence of NAD or NADP 15-18% of the substrate was converted to cortisone: no other products could be detected. No cortisol metabolism could be detected upon the addition of NADH or NADPH. Kinetic studies of the dependency of cortisone formation upon incubation time, tissue and substrate concentrations showed that 11 beta-hydroxy steroid dehydrogenase activity in homogenates of adipose tissue if taken from the non-obese and obese patients is similar. The possible significance of 11 beta-hydroxy steroid dehydrogenase activity in adipose tissue is discussed.     

Factors controlling fat mobilization from human subcutaneous adipose tissue during exercise

To investigate possible factors that limit fat utilization during exercise, arteriovenous differences of plasma nonesterified fatty acids (NEFA) and glycerol were measured across the subcutaneous adipose tissue of the anterior abdominal wall in nine subjects who exercised for 60 min at 50-70% of their maximal O2 consumption. The large gradient of NEFA concentration from adipose tissue venous to arterial plasma increased throughout the exercise period. Maximal plasma NEFA concentrations in adipose venous drainage were reached postexercise (median 3,800 mumol/l), with a median NEFA-to-albumin molar ratio of 5.7. Fractional reesterification of fatty acids within the tissue (assessed from the ratio of NEFA to glycerol release) was 20-30% in the basal state and declined during exercise. After exercise there was apparently negative reesterification, implying release of NEFA retained in adipose tissue during exercise. Although these findings challenge current views on the regulation of NEFA release, they are in agreement with the concept of supply of fatty acids from adipose tissue as the major factor limiting fat oxidation during sustained exercise.     

Interindividual variation in abdominal subcutaneous and visceral adipose tissue: influence of measurement site.

We evaluated the influence of measurement site on the ranking (low to high) of abdominal subcutaneous (SAT) and visceral (VAT) adipose tissue. We also determined the influence of measurement site on the prediction of abdominal SAT and VAT mass. The subjects included 100 men with computed tomography (CT) measurements at L4-L5 and L3-L4 levels and 100 men with magnetic resonance imaging (MRI) measurements at L4-L5 and 5 cm above L4-L5 (L4-L5 +5 cm). Corresponding mass values were determined by using multiple-image protocols. For SAT, 90 and 92 of the 100 subjects for CT and MRI, respectively, had a difference in rank position at the two levels. The change in rank position exceeded the error or measurement for approximately 75% of the subjects for both methods. For VAT, 91 and 95 of the 100 subjects for CT and MRI, respectively, had a difference in rank position at the two levels. The change in rank position exceeded the error of measurement for 36% of the subjects for CT and for 8% of the subjects for MRI. For both imaging modalities, the variance explained in SAT and VAT mass (kg) was comparable for L4-L5, L4-L5 +5 cm, and L3-L4 levels. In conclusion, the ranking of subjects for abdominal SAT and VAT quantity is influenced by measurement location. However, the ability to predict SAT and VAT mass by using single images obtained at the L4-L5, L4-L5 +5 cm, or L3-L4 levels is comparable.     

Regional differences in carboxylesterase activity between human subcutaneous and omental adipose tissue

Human adipose tissue was shown to contain carboxylesterase activity when measured by methylbutyrate as substrate. The enzyme has the same characteristics as carboxylesterase purified from rat epididymal adipose tissue. Like lipoprotein lipase, carboxylesterase activity was higher in large than in small fat cells. Both cell size and carboxylesterase activity were greater in human subcutaneous than in omental adipose tissue. However, the linear regression lines between the enzyme activity and cell volume in the two tissues were almost superimposable, suggesting that cell size is a determinant of enzyme activity. Although the physiological significance of adipose tissue carboxylesterase must await further clarification, it is possible that the enzyme is related to the hydrolysis of long-chain monoacylglycerols.     

Visfatin mRNA expression in human subcutaneous adipose tissue is regulated by exercise

Visfatin [pre-beta-cell colony-enhancing factor (PBEF)] is a novel adipokine that is produced by adipose tissue, skeletal muscle, and liver and has insulin-mimetic actions. Regular exercise enhances insulin sensitivity. In the present study, we therefore examined visfatin mRNA expression in abdominal subcutaneous adipose tissue and skeletal muscle biopsies obtained from healthy young men at time points 0, 3, 4.5, 6, 9, and 24 h in relation to either 3 h of ergometer cycle exercise at 60% of Vo(2 max) or rest. Adipose tissue visfatin mRNA expression increased threefold at the time points 3, 4.5, and 6 h in response to exercise (n = 8) compared with preexercise samples and compared with the resting control group (n = 7, P = 0.001). Visfatin mRNA expression in skeletal muscle was not influenced by exercise. The exercise-induced increase in adipose tissue visfatin was, however, not accompanied by elevated levels of plasma visfatin. Recombinant human IL-6 infusion to mimic the exercise-induced IL-6 response (n = 6) had no effect on visfatin mRNA expression in adipose tissue compared with the effect of placebo infusion (n = 6). The finding that exercise enhances subcutaneous adipose tissue visfatin mRNA expression suggests that visfatin has a local metabolic role in the recovery period following exercise.     

Lower thigh subcutaneous and higher visceral abdominal adipose tissue content both contribute to insulin resistance

It is well known that visceral adipose tissue (VAT) is associated with insulin resistance (IR). Considerable debate remains concerning the potential positive effect of thigh subcutaneous adipose tissue (TSAT). Our objective was to observe whether VAT and TSAT are opposite, synergistic or additive for both peripheral and hepatic IR. Fifty-two volunteers (21 male/31 female) between 30 and 75 years old were recruited from the general population. All subjects were sedentary overweight or obese (mean BMI 33.0 ± 3.4 kg/m(2)). Insulin sensitivity was determined by a 4-h hyperinsulinemic-euglycemic clamp with stable isotope tracer dilution. Total body fat and lean body mass were determined by dual X-ray absorptiometry. Abdominal and mid-thigh adiposity was determined by computed tomography. VAT was negatively associated with peripheral insulin sensitivity, while TSAT, in contrast, was positively associated with peripheral insulin sensitivity. Subjects with a combination of low VAT and high TSAT had the highest insulin sensitivity, subjects with a combination of high VAT and low TSAT were the most insulin resistant. These associations remained significant after adjusting for age and gender. These data confirm that visceral excess abdominal adiposity is associated with IR across a range of middle-age to older men and women, and further suggest that higher thigh subcutaneous fat is favorably associated with better insulin sensitivity. This strongly suggests that these two distinct fat distribution phenotypes should both be considered in IR as important determinants of cardiometabolic risk.     

Circulating levels of persistent organic pollutants in relation to visceral and subcutaneous adipose tissue by abdominal MRI

Objective:

We and others have shown relationships between circulating levels of persistent organic pollutants (POPs) and different measures of obesity in both cross‐sectional and prospective studies. Since viscerally located fat seems to be the most harmful type, we investigated whether plasma POP levels were more closely related to visceral adipose tissue (VAT) than to subcutaneous adipose tissue (SAT).

Design and Methods:

Thousand hundred and sixteen subjects aged 70 years were investigated in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study; 23 POPs were analyzed using high‐resolution gas chromatography/high‐resolution mass spectrometry. Abdominal magnetic resonance imaging, measuring VAT and SAT, respectively, was performed in a representative subsample of 287 subjects.

Results:

The less chlorinated polychlorinated biphenyl (PCB) congeners (105 and 118), and the pesticides dichlorodiphenyldichloroethylene (DDE), hexachlorobenzene (HCB), and trans‐nonachlordane (TNC) were positively related to both VAT and SAT, whereas the more highly chlorinated PCBs (153, 156, 157, 169, 170, 180, 194, 206, and 209) were inversely related to both VAT and SAT. PCB189 was related to the VAT/SAT ratio in an inverted U‐shaped manner (P = 0.0008).

Conclusions:

In conclusion, the results were in accordance with our previous studies using waist circumference and fat mass as obesity measure. However, the novel finding that PCB189 was related to the VAT/SAT ratio deserves further investigation since exposure to this PCB congener, which has previously been linked to diabetes development, might thereby play a role in the distribution of abdominal adipose tissue.