Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110
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ABSTRACT |
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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
mass1 · 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.
lipolysis; catecholamine; adipose tissue blood flow; stable isotopes; pancreatic clamp
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INTRODUCTION |
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EPINEPHRINE IS THE major plasma hormone that stimulates lipolysis of adipose tissue triglycerides. In lean persons, the lipolytic threshold to epinephrine is low, and a progressive increase in circulating epinephrine causes a progressive increase in lipolysis (14). Although persons with upper body obesity (UBO) have higher whole body basal lipolytic rates than lean persons, studies performed in vivo have found that their lipolytic response to epinephrine is blunted (7, 24). However, these in vivo findings are confounded by hyperinsulinemia associated with obesity, which could attenuate the lipolytic response to epinephrine (6). In addition, these studies did not evaluate whether regional differences in the lipolytic response to epinephrine exist in vivo between lean and obese subjects.
Epinephrine is also an important regulator of adipose tissue blood flow
(ATBF), which modulates fatty acid delivery from adipose tissue into
the systemic circulation. Simultaneous increases in lipolysis and ATBF
may be advantageous by enhancing the removal of free fatty acid (FFA)
released during lipolysis from the interstitial space and preventing
local accumulation of FFA (10, 37). In lean persons, basal ATBF is
lower in femoral than in abdominal subcutaneous fat depots (11). In
addition, abdominal basal ATBF is lower in obese than in lean persons,
whereas femoral ATBF is similar in both groups (11, 20). It is possible
that regional and adiposity-related differences in vascular
-adrenergic sensitivity may explain these differences in ATBF.
However, regional ATBF sensitivity to epinephrine has not been
evaluated in lean and obese persons.
The principal purpose of the present study was to evaluate whole body and regional lipolytic and ATBF sensitivity to a physiological range of plasma epinephrine concentrations in lean and UBO women. A pancreatic hormonal clamp (27) was used to eliminate differences in plasma insulin concentration between lean and obese groups and to prevent epinephrine-stimulated insulin secretion (14). In addition, the hormonal clamp allowed us to evaluate the influence of basal hyperinsulinemia on lipid metabolism in women with UBO.
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METHODS |
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Subjects.
Ten women with UBO [body mass index (BMI) >32
kg/m2; >40% body wt as fat; waist-to-hip ratio
>0.85; waist circumference >100 cm] and eight lean women (BMI
<24 kg/m2; <30% body wt as fat) participated in this
study (Table 1). Fat mass (FM) and fat-free
mass (FFM) were determined by dual-energy X-ray absorptiometry (Hologic
QDR 1000/W). Although all women were premenopausal, obese women (37 ± 2 yr old) were older than the lean women (26 ± 3 yr old; P < 0.05). All subjects were considered to be in good health after a
comprehensive medical examination, which included a history and
physical examination, blood tests, and an electrocardiogram. Obese
subjects had normal glucose tolerance based on a 2-h oral glucose
tolerance test. No subjects were taking any medications, and all were
weight stable for at least 2 mo before the study, which was performed
within the first 2 wk of the follicular phase of their menstrual cycle.
Written informed consent was obtained before participation in the
study, which was approved by the Human Studies Committee and the
General Clinical Research Center (GCRC) Scientific Advisory Committee
of Washington University School of Medicine.
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Experimental protocol.
Subjects were admitted to the GCRC at Washington University School
of Medicine in the evening before the day of the study. At 1900 on the
day of admission, subjects ingested a standard meal (55%
carbohydrate, 30% fat, and 15% protein) containing 12 kcal/kg body
wt for lean subjects and 12 kcal/kg adjusted body wt for obese subjects
{adjusted body wt = ideal body wt + [(actual body wt ideal body wt) × 0.25]}. Therefore, this
meal contained ~700 and ~800 kcal for lean and obese subjects,
respectively. At 2230, subjects ingested a liquid formula snack
containing 80 g carbohydrate, 12.2 g fat, and 17.6 g protein (Ensure;
Ross Laboratories, Columbus, OH). After this snack, the subjects fasted
until completion of the study.
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Hormonal clamp.
At 150 min of the study, a pancreatic hormonal clamp was
initiated by infusing somatostatin (0.17 µg · kg
FFM
1 · min
1;
Bachem Feinchemikalien, Bubendorf, Switzerland), insulin (0.08 mU · kg
FFM
1 · min
1;
Novo Nordisk Pharmaceuticals, Princeton, NJ), and growth hormone (0.00375 µg · kg
FFM
1 · min
1;
Genentech, San Francisco, CA; Fig. 1). Plasma glucose concentration was
monitored every 10 min between
150 and
15 min, and 20%
dextrose was infused as needed between
150 and
60 min to
maintain baseline blood glucose concentration. By
60 min,
euglycemia was maintained in all subjects without infusing dextrose.
Therefore, dextrose was not infused during the last 4.5 h (
60 to
210 min) of the hormonal clamp.
Epinephrine infusion.
At 0 min, a four-stage epinephrine infusion was started. Epinephrine
(Lederle Laboratories, Chicago, IL) was infused for 30 min at 0.00125 µg · kg
FFM1 · min
1
(Epi-1), 0.005 µg · kg
FFM
1 · min
1
(Epi-2), 0.0125 µg · kg
FFM
1 · min
1
(Epi-3), and 0.025 µg · kg
FFM
1 · min
1
(Epi-4) in discrete stages separated by a 30-min period without epinephrine infusion to reestablish basal epinephrine concentration and
lipolytic rates (Fig. 1). Ascorbic acid (0.5 mg/ml; Abbot Laboratories,
Chicago, IL) was added to the epinephrine infusate to prevent degradation.
Blood sampling.
Blood samples were obtained at 165,
160,
155, and
150 min (basal), at
15,
10,
5, and 0 min
(hormonal clamp baseline or "Pre-Epi"), and every 5 min during
each 30-min epinephrine infusion stage (Epi-1, Epi-2, Epi-3, and Epi-4;
Fig. 1). These samples were used to assess lipid kinetics and plasma
hormone concentrations during basal conditions, the hormonal clamp
baseline period, and each stage of epinephrine infusion.
Microdialysis. Four microdialysis probes (3-cm loop probes; BioAnalytical Systems, West Lafayette, IN) were placed in subcutaneous adipose tissue under local anesthesia. Two probes were placed in the abdominal region, ~3 cm lateral to the umbilicus, and two probes were placed in the femoral region, ~25 cm above the patella. Before insertion, the probes were flushed overnight (>16 h) with Ringer solution (with 2.5 mM glucose added) to remove any residual glycerol. Throughout the study, the probes were perfused with the same solution at a rate of 2 µl/min. Microdialysis samples were not collected for at least 3 h after insertion to avoid any influence of trauma due to probe placement. Microdialysis samples were collected during the 15-min period immediately before Epi-1 and during each epinephrine infusion (Fig. 1).
ATBF measurement. Abdominal and femoral subcutaneous ATBF was measured by the 133Xe clearance technique (28). At least 60 min before the first epinephrine infusion (during the hormonal clamp) ~100 µCi of 133Xe dissolved in 0.1 ml of normal saline were slowly injected over 60 s into abdominal and femoral subcutaneous adipose tissue. A cesium iodide detector (Oakfield Instruments, Eynsham, UK) was placed directly over the injection sites and was secured to the skin by tape. The decline in 133Xe was determined by collecting 10-s counts (36) beginning 15 min before Epi-1 and throughout each epinephrine infusion (Fig. 1).
Measurement of gas exchange. The rates of oxygen consumption and carbon dioxide production were measured during the basal period and during the hormonal clamp before the first epinephrine infusion (Fig. 1) by using a Vmax-29 metabolic cart (SensorMedics, Yorba Linda, CA).
Analytical procedures. Plasma insulin concentration was measured by RIA (16). Plasma catecholamine concentrations were determined by a radioenzymatic method (38). Glycerol concentration in the microdialysis samples was measured by a fluorometric method (9). Plasma glycerol concentration was determined by gas chromatography-mass spectrometry (GC-MS) and by adding [2-13C]glycerol to plasma as an internal standard. Plasma FFA concentrations were quantified by gas chromatography and by adding heptadecanoic acid to plasma as an internal standard.
Plasma glycerol and palmitate tracer-to-tracee ratios (TTR) were determined by GC-MS using an MSD 5971 system (Hewlett-Packard, Palo Alto, CA) with a capillary column (19, 33). Acetone was used to precipitate plasma proteins, and hexane was used to extract plasma lipids. The aqueous phase was dried by speed-vac centrifugation (Savant Instruments, Farmingdale, NY). Heptafluorobutyric (HFB) anhydride was used to form an HFB derivative of glycerol, and ions were produced by electron impact ionization. Glycerol TTR was determined by selectively monitoring ions at mass-to-charge ratio (m/z) 253, 254, and 257. FFAs were isolated from plasma and converted to their methyl esters with iodomethane. Ions at m/z 270.2 and 271.2, produced by electron impact ionization, were selectively monitored.Calculations. A plateau in substrate concentration and TTR was achieved during basal and hormonal clamp baseline periods. Therefore, glycerol and palmitate rates of appearance (Ra) in plasma and disappearance (Rd) from plasma during these time periods were calculated using Steele's equation for steady-state conditions (39). Total glycerol and palmitate Ra during each 30-min epinephrine infusion were calculated as the area under the Ra vs. time curve by using the non-steady-state equation of Steele (39). The effective volume of distribution was estimated to be 240 ml/kg for glycerol and 50 ml/kg for palmitate. FFA kinetics were calculated by dividing palmitate kinetics by the ratio of plasma palmitate to total plasma FFA concentration. The TTR and concentration data were smoothed by spline fitting (41). Nonoxidative fatty acid disposal was calculated as FFA Rd (determined by isotope tracer infusion) minus fatty acid oxidation (FAO; determined by indirect calorimetry; see Ref. 13).
Subcutaneous ATBF was calculated from 133Xe clearance (28)
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Statistical analysis.
A two-way ANOVA (subject phenotype × epinephrine dose) with
Tukey's post hoc analysis was used to test the significance of differences in lipid kinetics and plasma hormone concentrations between
lean and obese groups. A two-way ANOVA (anatomical site × epinephrine dose) with Tukey's post hoc analysis was used to test
the significance of differences in ATBF and regional lipolysis between abdominal and femoral adipose tissue in both groups. A Student's t-test for independent samples was used to test the significance of differences in fat oxidation, nonoxidative fatty acid
disposal rate, and subject characteristics between lean and obese
subjects. A value of P 0.05 was considered to be
statistically significant. All data are expressed as means ± SE.
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RESULTS |
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Plasma hormone concentrations.
Mean basal plasma insulin concentration was more than twofold greater
in obese than in lean women (22.3 ± 3.0 and 9.0 ± 1.0 µU/ml,
respectively; P < 0.05). During the baseline period of the
hormonal clamp, plasma insulin concentration decreased to similar
values in both obese and lean groups before epinephrine infusion (4.1 ± 0.3 and 4.4 ± 0.5 µU/ml, respectively) and remained low for the
remainder of the study in both groups (Fig.
2A). The graded epinephrine
infusion resulted in a progressive increase in plasma epinephrine
concentration, which was identical in obese and lean groups (Fig.
2B). Plasma norepinephrine concentration was not affected by
epinephrine infusion and remained at basal values throughout the study
(0.94 ± 0.11 and 1.13 ± 0.12 nM for obese and lean, respectively;
P = not significant).
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Whole body glycerol and FFA kinetics.
Basal FFA Ra and glycerol Ra were >25%
greater in obese compared with lean subjects (P < 0.05; Table
2). However, basal FFA and glycerol
Ra expressed relative to FM were approximately twofold greater in lean than obese subjects (P < 0.05). Basal FFA and glycerol Ra expressed relative to FFM were slightly greater
in obese than lean subjects, but the differences were not statistically significant.
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Regional glycerol kinetics.
The multistage epinephrine infusion increased glycerol release from
abdominal and femoral subcutaneous adipose tissue in lean and obese
subjects (main effect for epinephrine P < 0.05). However, the
increase in abdominal adipose tissue glycerol release was blunted in
obese compared with lean subjects (P < 0.05; Fig.
6A). In contrast, femoral adipose
tissue lipolytic activity during epinephrine infusion was similar in
lean and obese subjects (Fig. 6B). In lean but not obese
subjects, the increase in glycerol release was greater in abdominal
than femoral subcutaneous adipose tissue during the final two stages of
epinephrine infusion (Epi-3: 0.52 ± 0.13 vs. 0.23 ± 0.08;
Epi-4: 0.67 ± 0.15 vs. 0.18 ± 0.08 µmol · 100 g1 · min
1,
respectively; both P < 0.05).
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Regional ATBF.
Epinephrine infusion increased abdominal and femoral ATBF in both lean
and obese subjects (main effect for epinephrine P < 0.05).
The increase in abdominal ATBF was blunted in obese compared with lean
subjects (P < 0.05; Fig.
7A), whereas the increase in femoral ATBF was similar in lean and obese groups (Fig. 7B).
Compared with abdominal ATBF, the increase in femoral ATBF in response to epinephrine was blunted in lean subjects; femoral ATBF was significantly lower than abdominal ATBF during the final two stages of
epinephrine infusion (Epi-3: 4.4 ± 0.6 vs. 6.4 ± 0.7;
Epi-4: 4.4 ± 0.6 vs. 7.4 ± 0.5 ml · 100 g1 · min
1,
respectively; both P < 0.05). In obese subjects, abdominal
and femoral ATBF were similar during each stage of epinephrine
infusion.
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Fat oxidation.
Basal FAO tended to be greater in obese than in lean subjects, but the
difference was not statistically significant (P = 0.24; Table
3). During the baseline period of the
hormonal clamp, FAO increased above basal values in both groups
(P < 0.05). In obese subjects, the increase in FAO (~50
µmol/min) was much less than the increase in FFA Rd
(~350 µmol/min). Therefore, the rate of nonoxidative fatty acid
disposal almost tripled in obese women (P < 0.05) and was
more than fourfold greater than that observed in lean women (P < 0.05; Table 3). In lean subjects, the increase in FAO (~60
µmol/min) was similar to the increase in FFA Ra (~60 µmol/min), so nonoxidative fatty acid disposal did not change.
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DISCUSSION |
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The mobilization of adipose tissue lipids involves triglyceride hydrolysis and removal of released FFA by local blood vessels for delivery into the systemic circulation. Epinephrine is an important regulator of adipose tissue metabolism because it stimulates both lipolysis and ATBF (37). In the present study, we evaluated whether whole body and regional adipose tissue lipolytic and blood flow responses to a physiological range of plasma epinephrine concentrations were altered in women with UBO compared with lean women. A multistage epinephrine infusion was performed in conjunction with a pancreatic hormonal clamp to regulate plasma epinephrine concentrations while preventing the confounding influence of hyperinsulinemia associated with UBO (29) and epinephrine infusion (14). Our data demonstrate that whole body lipolytic sensitivity is blunted in women with UBO because of a decreased response to epinephrine in upper body (abdominal) but not lower body (femoral) subcutaneous fat depots. In addition, vascular sensitivity to epinephrine was blunted in abdominal but not femoral subcutaneous adipose tissue in women with UBO. These findings help explain the blunted increase in lipolysis observed in persons with UBO during physiological conditions that cause an increase in plasma epinephrine concentration and a decrease in plasma insulin concentration, such as fasting (19) and exercise (25).
The mechanism responsible for the blunted adipose tissue lipolytic and
vascular responses to epinephrine in persons with UBO may be related to
alterations in 2-adrenergic receptor number and/or
function. Adrenergic regulation of adipose tissue triglyceride lipolysis is mediated through
(stimulatory)- and
2
(inhibitory)-adrenergic receptors (40). It has been proposed that
differences in the lipolytic response to catecholamines in obese
compared with lean subjects is due to variations in the functional
balance between
- and
2-adrenergic receptors in
adipose tissue (30, 31). Reynisdottir et al. (35) found that lipolytic
sensitivity to norepinephrine was suppressed in fat cells obtained from
women with UBO, whereas lipolytic sensitivity to
1- and
2-adrenergic receptor agonists was the same in fat cells
obtained from lean and UBO subjects. The reduced lipolytic sensitivity
to catecholamines was attributed to a posttranscriptional reduction in
2-adrenergic receptor density (35). Therefore, data from
in vitro studies suggest that the blunted lipolytic sensitivity to
epinephrine observed in our subjects with UBO may be due to reduced
2-adrenergic receptor density, perhaps predominantly in
abdominal subcutaneous adipose tissue.
Previous studies performed in lean subjects found that the lipolytic
response to catecholamines is greater in upper body than in lower body
subcutaneous adipose tissue depots (15, 22, 30, 40). The major
determinant for the regional differences in catecholamine-stimulated
lipolysis is an increased sensitivity to -adrenergic stimulation in
upper body subcutaneous adipose tissue (15, 40) due to an increase in
2-adrenergic receptor density (40). However, increased
lower body adipose tissue
2-adrenergic receptor activity
may also contribute to the regional variation in lipolytic sensitivity,
particularly in women (30, 40). Jensen and colleagues (15, 22) found
that lower body adipose tissue lipolysis in women did not increase at
all during catecholamine infusion. In contrast, we found that, although
lipolytic sensitivity was blunted in femoral compared with abdominal
adipose tissue, femoral adipose tissue lipolysis nearly doubled during
epinephrine infusion. The reason for the differences observed between
our studies may be related to differences in study design. The
lipolytic response to epinephrine infusion peaks at ~30 min and then
declines toward baseline because of increased insulin secretion and
possibly
-adrenergic receptor tachyphylaxis (2, 23, 26, 37). In the
studies performed by Jensen and colleagues, lower body adipose tissue
lipolytic rate was measured between 60 and 90 min of the catecholamine
infusion and thus after completion of the peak lipolytic response. In
our study, we measured femoral adipose tissue lipolysis during the
first 30 min of epinephrine infusion and administered somatostatin to
prevent the normal increase in insulin secretion.
Our data demonstrate that the heterogeneity in adipose tissue lipolytic
sensitivity to catecholamines observed in lean persons is attenuated in
persons with UBO. The cause for this blunted lipolytic sensitivity in
abdominal subcutaneous adipose tissue in our obese subjects is unclear.
To our knowledge, no study has evaluated adrenergic receptor density in
upper and lower body subcutaneous adipose tissue in persons with UBO.
However, recent evidence indicates that adipocyte -receptor density
is similar in both upper and lower body subcutaneous adipose tissue
regions when adipocyte volume is similar (3). It is possible that the large fat cell size in abdominal subcutaneous adipose tissue in persons
with UBO (35) may reduce
-adrenergic receptor density and lipolytic
sensitivity to
-adrenergic stimulation.
Stimulation of 2-adrenergic receptors in vascular smooth
muscle reduces vascular tone and increases blood flow (17). ATBF sensitivity to epinephrine was blunted in the abdominal but not the
femoral region of our obese subjects compared with our lean subjects.
Therefore, regional ATBF sensitivity to epinephrine parallels the
increase in lipolytic sensitivity. These data support the notion that
the regulation of ATBF and lipolysis is coordinated to enhance the
delivery of newly released FFA into plasma and to prevent local
accumulation of excessive and potentially toxic FFA (10, 37).
Presumably, the coordinated increase in lipolysis and ATBF by
epinephrine is a consequence of
2-adrenergic
stimulation, both in adipocytes and adipose tissue blood vessels.
Recently, we found that lipolysis and abdominal ATBF in lean men
increased in a coordinated manner at low to moderate epinephrine
concentrations but not at concentrations >3 nM, when the increase in
ATBF was attenuated (18). In the present study, abdominal ATBF
increased proportionately to the increase in lipolysis during all
stages of epinephrine infusion in our female subjects, but plasma
epinephrine concentration did not exceed 2.2 nM. However, our study
does not rule out the possibility of gender-related differences in ATBF regulation by epinephrine.
Persons with UBO have greater basal whole body lipolytic rates than lean persons (19, 24, 29). The results of the present study suggest that the increase in lipolysis is probably caused by adipose tissue insulin resistance rather than enhanced sensitivity to catecholamines. However, persons with UBO are not completely resistant to the antilipolytic effect of insulin, and basal hyperinsulinemia may be an important mechanism for preventing even higher lipolytic rates from occurring. We found that, when plasma insulin concentrations were decreased in our obese subjects to match those found in our lean subjects during the hormonal clamp baseline period, whole body glycerol and FFA Ra increased to values double those of our lean subjects. Therefore, basal hyperinsulinemia, which helps normalize plasma glucose concentrations in obese persons, also helps control lipolytic activity.
Excessive lipolytic rates, in conjunction with liver and muscle uptake of FFA that is not oxidized, may be a principal contributor to the metabolic abnormalities found in persons with UBO (4, 34). We found basal nonoxidized fatty acid disposal to be >50% greater in obese than lean subjects. Reducing plasma insulin concentration during the baseline period of the hormonal clamp caused similar increases in FFA Rd and FAO in our lean subjects. However, the increase in FFA Rd during the baseline period of the hormonal clamp did not cause an equivalent increase in FAO in our obese subjects. It is likely that the marked increase in lipolysis and FFA availability overwhelmed the capacity for FAO during resting conditions. Moreover, the difference in nonoxidative fatty acid disposal rates between lean and obese subjects was probably greater than our estimated values. Our calculation of nonoxidized fatty acid disposal may underestimate the true disposal rate because a portion of fatty acids derived from intramuscular, intra-abdominal, and plasma triglycerides might be oxidized without entering the circulation and would not be detected by tracer infusion. Compared with lean persons, persons with UBO have greater intramuscular triglyceride stores (34), intra-abdominal fat (31), and plasma triglyceride concentrations (24) and presumably greater rates of undetected FFA release.
We attempted to minimize the confounding influence of alterations in insulin secretion and simplify subject participation by performing a multistage epinephrine infusion with a pancreatic hormonal clamp on one day. However, this experimental design may have some limitations. First, the decrease in plasma insulin concentration during the pancreatic hormonal clamp may have affected the lipolytic response to epinephrine in our obese subjects. The pancreatic hormonal clamp allowed us to match plasma insulin concentrations in lean and obese subjects and to evaluate the effect of different plasma epinephrine concentrations on lipolysis and ATBF independently of changes in plasma insulin that normally occur during epinephrine infusion. The rate of insulin infusion was chosen to maintain euglycemia and basal lipolytic rates in our lean subjects. Therefore, the relative decrease in plasma insulin concentration was much greater in our obese than in our lean subjects. The marked decline in circulating insulin in the obese group may have caused maximal stimulation of lipolysis and may have prevented further increases in lipolytic rate during epinephrine infusion. However, during the hormonal clamp baseline period, glycerol and FFA Ra expressed relative to body FM were one-half as great in the obese than in the lean group, suggesting additional capacity for lipolysis. Second, infusing epinephrine in four discrete stages on the same day might reduce the lipolytic response to epinephrine during the later stages because of tachyphylaxis (2). However, Divertie et al. (8) found that lipolytic rates were not different when a four-stage sequential epinephrine infusion with pancreatic hormonal clamp was performed on a single day compared with when the same epinephrine infusions were performed on four separate days.
In summary, whole body lipolytic sensitivity to epinephrine was blunted in women with UBO compared with lean women, due in large part to reduced lipolytic sensitivity in abdominal subcutaneous adipose tissue. Additionally, although basal lipolytic activity is elevated in women with UBO, the presence of hyperinsulinemia prevents basal lipolysis from increasing to very high rates. Therefore, reduced adipose tissue lipolytic sensitivity to epinephrine in conjunction with basal hyperinsulinemia has beneficial effects by limiting excessive rates of lipolysis and FFA release into the systemic circulation.
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ACKNOWLEDGEMENTS |
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We thank Renata Braudy and the nursing staff of the General Clinical Research Center for help in performing the experimental protocols, Dr. Guohong Zhao and Weqing Feng for their technical assistance, and the study subjects for participating in this study.
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FOOTNOTES |
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This study was supported by National Institutes of Health Grants DK-49989, DK-37948, RR-00036, RR-00954, AG-00078 and AG-13629.
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Address for reprint requests and other correspondence: S. Klein, Washington Univ. School of Medicine, 660 S. Euclid Ave., Box 8127, St. Louis, MO 63110-1093.
Received 2 June 1999; accepted in final form 13 January 2000.
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