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Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods and Procedures
  5. Results
  6. Discussion
  7. ACKNOWLEDGEMENT
  8. DISCLOSURE
  9. References

Upper-body/visceral obesity is associated with abnormalities of free fatty acid (FFA) metabolism and greater risk of developing type 2 diabetes compared with lower-body obesity. In lean subjects lipolysis is readily suppressed by insulin; however, metabolic inflexibility with respect to antilipolysis is a frequent finding in obesity, partly determined by body composition. This study investigates effects of insulin on regional adipose tissue lipolysis and lactate levels in upper-body overweight/obese (UBO), lower-body overweight/obese (LBO), and lean women. The microdialysis technique was used to assess adipose tissue glycerol and lactate concentrations in abdominal and femoral fat during a 5-h basal period and a 2-h hyperinsulinemic euglycemic clamp. The main findings were that the antilipolytic effect of insulin was attenuated in abdominal fat of UBO (glycerol reduction, abd (%): UBO 40.4 (−14 to 66), LBO 46.0 (−8 to 66), lean 66.2 (2–78), ANOVA, P < 0.05), and in femoral fat in both obese groups (glycerol reduction, fem (%): UBO 44.4 (35–67), LBO 44.4 (0–63), lean 65.0 (43–79), ANOVA, P < 0.05). Further, abdominal fat insulin-mediated increase in lactate concentration was greater in lean women compared with UBO women (lactate increase, abd (%): UBO −6.1 (−37.1 to 57.4), LBO 16.5 (−32.2 to 112.5), lean 51.4 (−45.7 to 162.9), P < 0.05), whereas no differences were found between groups in femoral fat (lactate increase, fem (%), UBO −12.9 (−43 to 24), LBO 12.7 (−30.7 to 92), lean 27.6 (−9.5 to 123.8), not significant). Respiratory exchange ratio (RER) increased significantly and similarly in all groups. So, UBO women were metabolically inflexible with respect to insulins antilipolytic and lactate increasing effects in abdominal adipose tissue. These phenomena are probably both consequences of insulin resistance of adipose tissue.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods and Procedures
  5. Results
  6. Discussion
  7. ACKNOWLEDGEMENT
  8. DISCLOSURE
  9. References

Obesity, especially upper-body/visceral fat accumulation, is associated with increased risk of development of metabolic abnormalities, such as insulin resistance, type 2 diabetes, dyslipidemia, and hypertension (1,2,3). In lower-body (gluteal and leg) obesity the association is much less pronounced (4). Many of the metabolic abnormalities associated with upper-body obesity can be explained by increased free fatty acid (FFA) release (lipolysis) from adipose tissue, and can be reproduced by experimentally raising plasma FFA. In addition, insulin resistant obese and type 2 diabetic subjects display impaired flexibility with respect to shifting between glucose- and lipid-oxidation (metabolic inflexibility) (5).

Metabolic flexibility is by definition the preference for fat-oxidation during fasting and for carbohydrate in response to glucose (i.e., after a meal or during hyperinsulinemic euglycemic clamp). Systemically, metabolic flexibility can be illustrated by changes in respiratory exchange ratio (RER). Comparisons can only be performed if basal RER is not different between the investigated groups, as recently reviewed by Galgani et al. (6). Both skeletal muscle and adipose tissue affect metabolic flexibility. In skeletal muscle, which accounts for 80–90% of glucose disposal during insulin stimulation (7), changes in metabolic flexibility are related to altered mitochondrial content and function (8,9) as well as insulin sensitivity (9). Adipose tissue is less explored, but characteristics such as percent body fat, fat cell size, and insulin-suppressed FFA levels are negatively correlated to metabolic flexibility (10). Whereas RER reflects whole-body oxidative status, in situ methods such as microdialysis can be used to measure regional substrate metabolism, e.g., in adipose tissue in vivo. A positive correlation between glycerol release measured by in vivo (microdialysis) and in vitro (cell-culture) methods from adipose tissue of healthy subject has been demonstrated (11). Thus, the microdialysis technique is a suitable method to study potential heterogeneity between groups in muscle and adipose tissue in different compartments.

Using the microdialysis technique greater lipolytic rate has been shown in abdominal compared to femoral adipose tissue in lean and obese individuals both postabsorptively and during insulin stimulation following a glucose load (12) or a mixed meal (13). Furthermore, plasma lactate levels are elevated in obese subjects compared to lean subjects during fasting (14,15), and lack of flexibility with regard to lactate release rates has been suggested in obese subjects with insulin resistance (16). In a study of obese and lean men and women, similar rates of regional adipose tissue lipolysis and skeletal muscle lactate production was reported (17). However, sex specific differences in lipolysis are well documented (18). To our knowledge no comparison of upper- and lower-body obese women has been made with regard to flexibility in adipose tissue and muscle tissue.

The present study investigated glycerol and lactate changes as indicators of metabolic flexibility in regional adipose tissue. We used the microdialysis technique to assess changes in adipose tissue glycerol and lactate concentrations during a hyperinsulinemic euglycemic clamp in upper-body overweight/obese (UBO), lower-body overweight/obese (LBO), and lean premenopausal women. Indirect-calorimetry was used to measure whole-body RER. We hypothesized that obese women would be more insulin resistant than lean women and therefore present with less antilipolysis as well as less lactate increase in response to hyperinsulinemia. We expected this outcome to be more pronounced in the abdominal subcutaneous fat as compared to leg fat in both groups of obese women.

Methods and Procedures

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods and Procedures
  5. Results
  6. Discussion
  7. ACKNOWLEDGEMENT
  8. DISCLOSURE
  9. References

The local ethics committee approved the study and informed written consent was obtained from all participants before entering the study.

Thirty-one healthy, premenopausal women (10 UBO, 11 LBO, and 10 lean) were included in the study. Upper- and lower-body overweight/obesity was defined as BMI >28 kg/m2 in combination with waist-to-hip ratio (WHR) >0.85 (UBO) or a WHR <0.80 (LBO). Lean subjects were defined as BMI <25 kg/m2. All were studied in the luteal phase. If there was uncertainty regarding their status as premenopausal (age >45 years), a blood sample was taken for determination of follicle-stimulating hormone (FSH) and estradiol, and subjects were excluded if FSH >10 IU/l and if estradiol <0.5 µmol/l. All participants were normotriglyceridemic, normotensive, nonsmokers, used no medication except oral contraceptives, and had normal blood count and chemistry panel documented before participation.

Experimental protocol

For each participant, weight maintaining meals (30% fat, 55% carbohydrate, 15% protein) were designed by a clinical dietician and provided from the hospital kitchen for 3 days before the study assuring consistent nutrient and energy intake. All maintained their usual level of physical activity and were asked not to participate in heavy exercise the last 3 days before the study. Throughout the examination day, the participants remained in bed wearing light hospital clothing in a room of ambient temperature of 22–24 °C.

Participants were admitted to the research laboratory at 2200 hours the evening before the study day. After an overnight fast intravenous catheters were inserted in a dorsal hand vein and in a cubital vein. The hand was placed in a heated box for collection of arterialized blood. Subcutaneous microdialysis catheters were placed in the subcutaneous adipose tissue at the abdomen lateral to umbilicus and at the anterior femoral site. The obese subjects had a solution of 1 MBq 133Xe (0.1 ml) injected subcutaneously at both regional sites and a NaI detector was placed to measure activity washout throughout the day for adipose tissue blood flow (ATBF) determination. Unfortunately, during the study 131Xe became unavailable from the supplier, so we were forced to give up measurements of 131Xe washout in lean women.

At 0800 hours (time 0) baseline blood samples were obtained. Microdialysis samples for determination of glycerol and lactate levels in adipose tissue were obtained at baseline and every half hour throughout the study (times: 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330, 360, 390, and 420). From 300 to 420 min a hyperinsulinemic euglycemic clamp was performed. Insulin was infused at a rate of 0.6 mU/kg/min. Plasma glucose was measured every 10 min using a Beckman analyzer (Beckmann Instruments, Palo Alto, CA) and clamped at ∼5 mmol/l by infusion of glucose 20%. Glucose infusion rate (M-value) reflects whole-body insulin sensitivity.

After completion of the study all catheters were removed. After stabilization of blood glucose, participants were dismissed.

Assays and methods

Glycerol and lactate concentrations were measured with an automated dialysate sample analyzer (Clinical Microdialysis Analyser (CMA) 600; CMA, Stockholm, Sweden). The microdialysis catheter (CMA 60; CMA) consists of a semipermeable polyamide membrane with cutoff of 20 kDa connected to the end of a double-lumen tube. The probe was inserted in the subcutaneous adipose tissue under local anesthesia and was continuously perfused at a rate of 1 µl/min using a precision pump (CMA 106; CMA) with a sterile solution containing 3H-glycerol. An exchange of metabolites takes place over the membrane, and the composition of the dialysates reflects the extracellular fluid (19). The added 3H-glycerol was used as internal standard to correct relative recovery. For one lean subject data from the microdialysis catheter on the abdomen was not available due to a technical error.

Resting energy expenditure and substrate oxidation rates were examined by indirect-calorimetry (Deltatrac monitor; Datex Instrumentarium, Helsinki, Finland) every hour and net lipid- and glucose-oxidation rates were calculated using the nonprotein RER from the above measurements (20).

Subcutaneous ATBF was measured in the obese subjects using the 133Xe washout method (3). The 133Xe washout slope and a partitioning coefficient between blood and adipose tissue of 10 ml/g were used for these calculations.

Total body fat, leg fat, fat percent and fat-free mass were examined by dual-energy X-ray assessment (QDR-2000, Hologic Discovery; Hologic, Bedford, MA). Upper-body and visceral fat were assessed using the combination of single-slice computed tomography scan at L2-L3 interspace and dual-energy X-ray assessment abdominal fat measurement (21). Upper-body subcutaneous fat was calculated as upper-body fat minus visceral fat. The computed tomography scan was technically insufficient in one UBO subject.

Plasma insulin was measured by a two-site immunospecific enzyme-linked immunosorbent assay. The intra and interassay coefficients of variation were 3 and 5%, respectively.

Calculation and statistics

Insulin-mediated interstitial glycerol suppression in percent was calculated as (1 - (glycerol level clamp/glycerol level basal)) × 100. Similarly, insulin-mediated interstitial lactate increase in percent was calculated as ((lactate level clamp/lactate level basal) × 100). Thus, changes in percent for both interstitial glycerol and lactate are expressed as positive values. Absolute changes for both glycerol and lactate were calculated as (clamp level—basal level), with the values being negative for decreases and positive for increases. The insulin-mediated changes are therefore described as either delta values or as percentage change in interstitial glycerol and lactate from the basal (nonstimulated) period to the hyperinsulinemic (stimulated) period. Substrate flow rates were calculated as ATBF × substrate concentration and expressed as nmol/100 g tissue/min.

Data are presented as mean ± s.d. or median ± range as appropriate. For comparisons between groups one-way ANOVA was used for the parametric data and Kruskall-Wallis for the nonparametric data. Within group comparisons were analyzed using Student's t-test. Prespecified outcome variables (basal glycerol and lactate concentration, difference in basal vs. insulin-stimulated glycerol and lactate concentration and differences between abdominal and femoral fat glycerol and lactate concentration) were not corrected for multiple comparisons. For all other comparisons of glycerol and lactate Bonferroni correction was applied. An uncorrected P value <0.05 was considered statistically significant.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods and Procedures
  5. Results
  6. Discussion
  7. ACKNOWLEDGEMENT
  8. DISCLOSURE
  9. References

Subject characteristics are given in Table 1.

Table 1.  Subjects characteristics
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Microdialysis

During the clamp steady state concentrations of both glycerol and lactate concentrations were documented (Figure 1a).

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Figure 1. Glycerol and lactate interstitial concentrations during the last 30 min (steady-state) of the clamp period. (a) Glycerol and (b) lactate concentrations during the last 30 min of the clamp period for UBO, LBO, and lean women. Squares: LBO, circles: UBO, triangles: Lean. LBO, lower-body overweight/obese; UBO, upper-body overweight/obese.

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Glycerol. Tissue concentrations are presented in Table 2. There were no significant differences in basal glycerol concentrations between the groups in abdominal or in femoral fat. Similarly, glycerol was not significantly different between groups during hyperinsulinemia in abdominal fat or in femoral fat.

Table 2.  Glycerol (µmol/l) and lactate (mmol/l) levels
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In abdominal fat glycerol concentration was significantly suppressed by hyperinsulinemia in LBO and lean women (both P < 0.001), whereas the reduction in UBO women was not significant. In femoral fat a significant suppression of glycerol concentration was observed during hyperinsulinemia in all groups (P < 0.001).

The percent change from basal in glycerol concentration during hyperinsulinemia was significantly greater in abdominal fat of lean women compared with UBO women (Figure 2). Similarly, the percent change was significantly greater in leg fat of lean women compared with both UBO and LBO women (Figure 2).

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Figure 2. Percent decrease in glycerol concentration during hyperinsulinemia in abdominal and femoral fat for UBO, LBO, and lean women. Horizontal lines represent median values, P < 0.05. LBO, lower-body overweight/obese; UBO, upper-body overweight/obese.

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Lactate. Tissue concentrations are shown in Table 2. No significant difference was noted in between groups in neither basal nor insulin-stimulated lactate concentrations in both abdominal and leg fat. Hyperinsulinemia did not result in significant changes in lactate concentrations in any of the groups. Percent change from baseline in abdominal lactate concentration during hyperinsulinemia was significantly greater in lean women compared with UBO women but not significantly different compared with LBO women (Figure 3). On the other hand, the percent change from baseline in femoral lactate during hyperinsulinemia was not statistically different between groups (Figure 3). Steady state in lactate concentrations were obtained in the last 30 min of the clamp period (Figure 1b).

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Figure 3. Percent increase in lactate concentrations during hyperinsulinemia in abdominal and femoral fat for UBO, LBO, and lean women. Horizontal lines represent median values, P < 0.05. LBO, lower-body overweight/obese; UBO, upper-body overweight/obese.

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In the combined group insulin-stimulated lactate changes in femoral fat, but not abdominal fat, correlated significantly with insulin sensitivity (M-value) (Figure 4). In the individual groups this correlation was only significant in abdominal fat of UBO women (r = 0.454, P = 0.01). Basal lactate concentration in abdominal fat correlated inversely with the M-value in the combined group, whereas the relationship was not significant in femoral fat (r = 0.331, P = 0.07). Correlations between lactate concentrations and M-value in the insulin-stimulated state were not significant.

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Figure 4. Lines representing correlations between percent increase in lactate and M-value. Squares: LBO, circles: UBO, triangles: Lean. Short-dash line: LBO, solid line: UBO, long-dash line: Lean. LBM, lean body mass; LBO, lower-body overweight/obese; UBO, upper-body overweight/obese.

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Indirect calorimetry

RER was not significantly different between the groups during the basal state (UBO 0.78 ± 0.04 vs. LBO 0.76 ± 0.06 vs. lean 0.79 ± 0.05, not significant) or during the clamp (UBO 0.90 ± 0.04 vs. LBO 0.90 ± 0.07 vs. lean 0.92 ± 0.07, not significant). The increase in RER from basal during hyperinsulinemia was significant in all groups (P < 0.001).

Insulin sensitivity and ATBF

Insulin sensitivity and ATBF data have been reported earlier (22,23). Insulin infusion (0.6 mU/kg/min) resulted in greater insulin concentrations in obese subjects (UBO 319.6 ± 23 vs. LBO 274.5 ± 13.5 vs. lean 199.9 ± 9.9 pmol/l (P < 0.001)). In both the UBO and LBO women, basal ATBF was significantly greater in femoral compared to abdominal adipose tissue but there was no significant difference between UBO and LBO women. Moreover, there was no significant difference in ATBF between abdominal and leg fat during hyperinsulinemia in any of the groups as well as no significant difference between UBO and LBO women.

Glycerol release rates. In UBO women glycerol release rates were similar in the basal state and the hyperinsulinemic state in both abdominal fat and leg fat and no significant difference between abdominal and femoral fat. Moreover, in the UBO women the change in glycerol release rate from basal during hyperinsulinemia was not significantly different between the abdominal and femoral fat.

In LBO women basal glycerol release rate was significantly greater in femoral fat than in abdominal fat (LBO: femoral 620 (308–1,269) vs. abdominal 311 (113–614) (nmol/100 g tissue/min), P < 0.05), whereas no such difference was observed during clamp. Moreover, in the LBO women the change in glycerol release rate from basal during hyperinsulinemia was not significantly different between abdominal and femoral fat. Overall, there were no significant differences in basal and insulin-stimulated glycerol release rates between UBO and LBO women.

Lactate release rates. In UBO women there were no differences between the basal state and the insulin-stimulated state or between the regions in either state. In LBO women basal lactate release rate was significantly greater in the femoral fat than in abdominal fat (LBO: femoral 4.9 (1.6–7.4) vs. abdominal 2.4 (0.6–16.4) (nmol/100 g tissue/min), P < 0.05), whereas this difference was not found during hyperinsulinemia. The change in lactate release rate from basal during hyperinsulinemia was not significantly different between abdominal and femoral fat. Similar to glycerol release rate there was we observed no significant differences in basal and insulin-stimulated lactate release rates between UBO and LBO women in either region or in either state.

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods and Procedures
  5. Results
  6. Discussion
  7. ACKNOWLEDGEMENT
  8. DISCLOSURE
  9. References

To our knowledge this study is the first to examine the effects of insulin on regional subcutaneous adipose tissue glycerol and lactate release in lean and obese women with different body composition. Compared with lean women, we found abdominal adipose tissue of UBO women to be insulin resistant with respect to suppression of glycerol release and stimulation of lactate release. In addition, femoral fat of both UBO and LBO women was resistant to insulin-mediated suppression of glycerol release compared with femoral fat of lean women, whereas no significant differences in lactate release were noted between the groups. However, these local differences were not sufficiently great to elicit differences in whole-body substrate oxidation as indicated by the equivalent changes in RER between groups.

Previous microdialysis studies of local substrate perturbations have shown interesting results; however, direct comparison of different obesity phenotypes are lacking. In sedentary obese premenopausal women, insulin was found to suppress glycerol release less in femoral fat but similarly in abdominal subcutaneous fat compared with sedentary lean and endurance trained women (10,24). In a different study, obese men and obese women were found to have greater interstitial glycerol levels in abdominal fat compared with lean men and women both after fasting and after an oral glucose load. Moreover, greater skeletal muscle glycerol concentrations were noted in the obese subjects; however, at concentrations only half of that found in adipose tissue (17). In men, interstitial glycerol concentration in abdominal and femoral subcutaneous fat was increased in obese men compared with lean men both postabsorptively and after a glucose load. Furthermore, in both groups greater postabsorptive glycerol concentrations were noted in abdominal fat compared with femoral fat, whereas abdominal and femoral fat concentrations were suppressed to the same level within each group (12,25). On the other hand, combining ATBF with interstitial glycerol concentration to calculate the apparent glycerol release rate have shown both greater (26) and similar (25) glycerol release in the obese men. In the former study, resistance exercise increased glycerol release (lipolysis) significantly more in lean than in obese subjects, indicating greater responsitivity of abdominal fat in the lean subjects.

Skeletal muscle has been established as a major determinant of plasma lactate, both through anaerobe glycolysis to yield energy but also at rest through insulin stimulation and insulin-mediated glucose uptake (27). Importantly, however, microdialysis studies suggests that adipose tissue does contribute significantly to lactate release (28). Hyperinsulinemia increases lactate production through glycolysis by conversion of pyruvate by lactate dehydrogenase in virtually all human tissues, both through anaerobic as well as aerobic conditions (27). In lean and obese women, lactate release from both adipose tissue and skeletal muscle has been demonstrated to be increased during hyperinsulinemia, and particularly adipose tissue showed a more pronounced increase in lactate release than skeletal muscle (29). Moreover, the authors also reported impaired insulin-mediated lactate release in both adipose tissue and skeletal muscle in obese women compared with lean women. In men, studies have shown that obese subjects have an impaired ability to increase interstitial lactate production during an oral glucose load (16). These data may indicate that in obese subjects, the adipose tissue may be relatively more important than skeletal muscle with respect to total release of lactate during hyperinsulinemia, maybe due to the relatively larger fat mass. In the present study, we extend this finding to the abdominal subcutaneous adipose tissue of UBO women, in whom we found a lesser insulin-mediated change in interstitial lactate concentration compared with lean women, whereas this difference was not observed in LBO women or in femoral fat. Insulin does, on the other hand, mediate postprandial increments in ATBF in lean men and women (30) and may, thus, play a role in regard to accurate estimates of substrate release is adipose tissue.

We found basal ATBF to be similar in UBO and LBO women but greater in femoral than abdominal fat. Moreover, insulin stimulation did not result in any significant change in ATBF in the obese subjects. These findings are supported by previous studies showing no effect of experimental hyperinsulinemia (29) or postprandial hyperinsulinemia (31) on nutritive blood flow in adipose tissue in obese and insulin resistant subjects. This indicates that insulin resistance is also characterized by diminished insulin-mediated changes in ATBF that should be considered when examining differences between obese and lean subjects in adipose tissue metabolism. In accordance, we found significantly greater basal glycerol and lactate release rates, but similar concentrations, in femoral fat compared with abdominal fat in LBO compared with UBO women. Overall, however, our data do not suggest that ATBF is a major determinant when comparing adipose tissue glycerol and lactate metabolism between UBO and LBO women, neither postabsorptively nor during experimental hyperinsulinemia.

Insulin regulation of regional lipolysis has also been assessed in UBO, LBO, and lean women (13). Splanchnic, upper-body nonsplanchnic, and leg FFA release rates were assessed before and after a mixed meal from measurements of plasma palmitate a-v tracer and concentration balances and blood flow after femoral artery, femoral vein, and hepatic vein catheterizations. The authors were able to show a diminished ability of insulin to suppress upper-body nonsplanchnic lipolysis in UBO obese women, whereas the effect on splanchnic and leg fat lipolysis were similar (13). The approach measures the contribution of regional adipose tissue effective lipolysis to the systemic lipolysis, i.e., the relative metabolic task carried out by a given fat depot. The methodology, does not allow reuptake of released fatty acids to be accounted for. Conversely, microdialysis measurements are typically expressed per unit weight and thus more suited to describe local adipose tissue function and perhaps more indicative of “absolute ” in situ lipolysis. This, as well as the present glycerol data, supports our hypothesis of less insulin-suppressed lipolysis in the abdominal subcutaneous fat of UBO women compared with lean and with leg fat. Moreover, we noted a linear relationship between the change in abdominal fat lactate concentration and insulin sensitivity (M-value) when all groups were combined (Figure 4), suggesting that, regardless of body composition and body weight, greater insulin sensitivity is associated with greater ability to increase lactate production in response to hyperinsulinemia. However, more studies performed in groups of subjects with a more homogeneous body weight and body composition are needed to confirm this hypothesis.

Some limitations of our study need to be addressed. First, we acknowledge the possibility of a type 2 error, since the number of participants might be too small to detect small differences in glycerol and lactate concentration in interstitial fluid. Moreover, since we were unable to measure ATBF in lean women we cannot extend our conclusions regarding substrate release rates to include lean women. Postabsorptive ATBF is reduced in obese as compared with lean individuals. Thus, the combination lower basal ATBF and less increase during hyperinsulinemia could partly explain the greater basal and insulin-stimulated interstitial glycerol concentrations, as well as the attenuated concentration change in response to hyperinsulinemia of obese women compared with lean women. The same argument can be used for basal lactate concentration, whereas the impaired increase in response to hyperinsulinemia cannot be explained by this mechanism, but can only be accounted for by a greater insulin-stimulated increase in lactate secretion in lean compared with obese women. In addition, interstitial glycerol may originate not only from adipocyte lipolysis but also from lipoprotein lipase hydrolysis of triglyceride rich lipoproteins, which would tent to overestimate adipose tissue lipolysis. However, as previously reported, lipoprotein lipase activity per gram of fat was not significantly different between the three groups of women (23). Moreover, visceral fat metabolism cannot be accounted for in this study due to the nature of the study design. Visceral adipose tissue is known to be lipolytically more active than other adipose tissue compartments and even less responsive to the antilipolytic effect of insulin than upper-body subcutaneous adipose tissue (32). However, subcutaneous adipose tissue has been proposed as an important determinant of metabolic flexibility regarding both fat and carbohydrate turnover, especially in obese subjects due to the relatively larger fat compartment than muscle compartment (33). Finally, it should be noted that the protocol prescribed an insulin infusion rate of 0.6 U/kg/min during the clamp. Adipose tissue of obese women was therefore subjected to higher insulin concentrations than adipose tissue of lean women and diminished insulin levels can therefore not explain the observed differences. Thus, it is possible that the higher insulin levels may in fact have blunted some of the differences in our results.

In summary, the present data emphasizes abdominal subcutaneous adipose tissue of UBO women as a site of local impaired flexibility concerning the metabolism of glycerol and lactate characterized by less ability to shut down lipolysis and less ability to increase lactate production through increased glycolysis in response to experimental hyperinsulinemia. Insulin resistant suppression of femoral fat lipolysis was present in both UBO and LBO women whereas lactate release was unaltered by obesity in femoral fat. The contribution of local metabolic inflexibility on whole-body substrate metabolism is not fully understood and needs further investigations.

ACKNOWLEDGEMENT

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods and Procedures
  5. Results
  6. Discussion
  7. ACKNOWLEDGEMENT
  8. DISCLOSURE
  9. References

We wish to thank Lene Ring, Lone Kvist, and Susanne Sørensen for excellent technical assistance. This work was supported by grants from the Danish Medical Research Council, the Novo Nordic Foundation, and the Danish Diabetes Foundation (to S.N.). Data have previously been presented in oral form at the NAASO annual meeting in New Orleans 2007.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods and Procedures
  5. Results
  6. Discussion
  7. ACKNOWLEDGEMENT
  8. DISCLOSURE
  9. References