Effect of short-term fasting on lipid kinetics in lean and
obese women
Jeffrey F.
Horowitz1,
Simon W.
Coppack2,
Deanna
Paramore1,
Philip E.
Cryer1,
Guohong
Zhao1, and
Samuel
Klein1
1 Department of Internal Medicine, Washington
University School of Medicine, St. Louis, Missouri 63110; and
2 University College London Medical School,
Whittington Hospital, London N19 3UA, United Kingdom
 |
ABSTRACT |
We evaluated whole body and regional adipose
tissue lipid kinetics and norepinephrine (NE) spillover during brief
fasting in six lean [body mass index (BMI) 21 ± 1
kg/m2] and six upper-body obese (UBO; BMI 36 ± 1
kg/m2) women. At 14 h of fasting, abdominal adipose tissue
glycerol and free fatty acid (FFA) release rates were lower
(P = 0.07), but whole body glycerol and FFA rates of
appearance (Ra) were greater (P < 0.05) in
obese than in lean subjects. At 22 h of fasting, glycerol and FFA
Ra increased less in obese (19.8 ± 7.0 and
87.1 ± 30.3 µmol/min, respectively) than in lean (44.2 ± 6.6 and 137.4 ± 30.4 µmol/min, respectively; P < 0.05)
women. The percent increase in glycerol Ra correlated
closely with the percent decline in plasma insulin in both groups
(r2 = 0.85; P < 0.05). Whole body NE
spillover declined in lean (P < 0.05) but not obese
subjects with continued fasting, whereas regional adipose tissue NE
spillover did not change in either group. We conclude that, compared
with lean women, in UBO women 1) basal adipose tissue
lipolysis is lower, but whole body lipid kinetics is higher
because of their greater fat mass; 2) the increase in
lipolysis during fasting is blunted because of an attenuated decline in
circulating insulin; and 3) downregulation of whole body
sympathetic nervous system activity is impaired during fasting.
lipid metabolism; sympathetic nervous system; stable isotopes; starvation; adipose tissue
 |
INTRODUCTION |
ADIPOSE TISSUE triglycerides are the body's major
source of fuel during periods of food deprivation. Therefore, increased mobilization of adipose tissue triglycerides is an important adaptive response to fasting. In lean adults, whole body lipolytic rates double
during a 3-day fast (19, 40), and most of this increase occurs between
12 and 24 h of fasting (19). However, the increase in whole body
lipolysis during 3 days of fasting is blunted in severely obese
subjects (40). The mechanism(s) responsible for the differences in the
lipolytic response to fasting in lean and obese subjects is not known
but must be related to alterations in the factors that regulate lipolysis.
Insulin and catecholamines are the two major hormones that
regulate lipolytic activity in humans. During fasting, a decline in
plasma insulin concentration (19, 31) and an increase in adipose tissue
resistance to the antilipolytic effect of insulin (14) enhance
lipolysis. In addition, increased adrenal medullary catecholamine
secretion (27) and increased adipose tissue lipolytic sensitivity to
catecholamines (40) contribute to an increase in
-adrenergic-mediated lipolysis (17). Although fasting causes a
decrease in whole body sympathetic nervous system (SNS) activity in
lean adults (43), the effect of fasting on adipose tissue SNS activity
is unknown. Heterogeneity in the SNS response of different tissues to
fasting could be advantageous by decreasing whole body SNS activity to
conserve energy (43) and increasing adipose tissue SNS activity to
enhance endogenous fuel mobilization.
In the present study, we evaluated whole body and abdominal
subcutaneous adipose tissue lipolytic rates, and the major factors that
regulate lipolyisis, in vivo during short-term fasting in lean and
obese women. Both stable and radioactive isotopes were infused to
evaluate lipid and norepinephrine (NE) kinetics. Subjects were studied
at 14 and 22 h of fasting because maximal changes in fasting-induced
lipolysis occur during this period (19). The obese group contained only
women with upper-body obesity (UBO) because of the increase in basal
lipolytic rates observed in this phenotype (24). We hypothesized that
the increase in lipolysis that occurs during fasting is blunted in
obese compared with lean women because of differences in circulating
insulin and adipose tissue SNS activity.
 |
METHODS |
Subjects.
Six women with UBO (>40% body wt as fat; waist-to-hip circumference
ratio >0.85, and waist circumference >100 cm; 38 ± 3 yr old)
and six lean women (<30% body wt as fat; 28 ± 2 yr old)
participated in this study (Table 1). Although all women
were premenopausal, the differences in age between lean and obese women
were statistically significant (P < 0.05). The obese and
lean subjects were matched for fat-free mass. Fat mass and fat-free
mass were determined by dual energy X-ray absorptiometry (QDR 1000/W;
Hologic, Waltham, MA). 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 participating in this study, which was approved by the
Institutional Review Board and the General Clinical Research Center of
Washington University School of Medicine.
Experimental procedure.
Subjects were admitted to the General Clinical Research Center at
Washington University School of Medicine in the evening before the
infusion study. At 1800, subjects ingested a standard meal 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 a total of ~700 and 800 kcal for the lean and obese women,
respectively. Carbohydrate, fat, and protein represented 55, 30, and
15%, respectively, of total energy intake. At 2000, subjects ingested
a defined liquid formula snack containing 250 kcal, 40 g carbohydrate,
6.1 g fat, and 8.8 g protein (Ensure, Ross Laboratories, Columbus, OH).
After this snack, all subjects fasted until completion of the study the
following day.
The following morning, 20-gauge catheters were inserted in a forearm
vein for isotope infusion and in a radial artery for arterial blood
sampling. A 22-gauge catheter (Hydrocath; Viggo-Spectramed, Oxnard, CA)
was placed in an abdominal vein draining abdominal subcutaneous adipose
tissue by using the Seldinger technique (4). The catheter was
positioned so that the tip was superior to the inguinal ligament as
judged by surface anatomy.
An overview of the infusion study protocol is shown in Fig.
1. At 0800 (12 h of fasting), a primed (1.5 µmol/kg), constant (0.10 µmol · kg
1 · min
1)
infusion of [1,1,2,3,3-2H]glycerol [99% atom percent
excess (APE); Cambridge Isotopes, Andover, MA] dissolved in 0.9%
saline was started and continued for 2 h using a calibrated syringe
pump (Harvard Apparatus, Natick, MA). At 0830, a constant infusion
(0.04 µmol · kg
1 · min
1) of [2,2-2H]palmitate (98% APE;
Cambridge Isotopes) bound to human albumin was started and continued
for 90 min. At 0930, a constant infusion (10 nCi · kg
1 · min
1)
of levo-[ring-2,5,6-3H]NE (New England Nuclear,
Boston, MA) was started and continued for 30 min. An arterial blood
sample was obtained before isotope infusion to determine background
tracer-to-tracee ratios and specific activity. Blood samples were
obtained from artery and abdominal vein simultaneously every 5 min
(four samples) between 0945 and 1000 (13 h 45 min and 14 h of fasting)
to determine plasma hormone concentrations, plasma substrate
concentrations, tracer-to-tracee ratios of glycerol and FFA, and NE
specific activity.

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Fig. 1.
Schematic diagram of study protocol. Isotope infusion studies were
timed to ensure completion of each study at precisely 14 and 22 h of
fasting. NE, norepinephrine; ATBF, adipose tissue blood flow.
|
|
All isotope infusions were stopped after obtaining the last blood
sample at 14 h of fasting, and catheters were kept patent by infusing
0.9% saline at 25 ml/h. Subjects remained in bed for an additional 8 h, and the infusion study protocol was repeated between 1600 and 1800 (20 and 22 h of fasting; Fig. 1).
Subcutaneous abdominal adipose tissue blood flow (ATBF) was measured by
the 133Xe clearance technique (20). Between 0830 and 0845, ~100 µCi of 133Xe dissolved in 0.15 ml of normal saline
were slowly injected over 60 s in subcutaneous adipose tissue, 3 cm
lateral to the umbilicus. A cesium iodide detector (Oakfield
Instruments LTD, Eynsham, UK) was placed directly over the site of
injection and was secured to the skin by tape. The decline in
133Xe was determined by collecting 10-s counts (30)
continuously for 15 min between 0945 and 1000 (13 h 45 min and 14 h of
fasting) and again between 1745 and 1800 (21 h 45 min and 22 h of fasting).
Analytical procedures.
Plasma insulin (8) and glucagon (9) concentrations were measured by
radioimmunoassay. Plasma catecholamine concentrations were determined
by a radioenzymatic method (32). Plasma fatty acid concentrations were
determined by gas chromatography (25).
Glycerol and palmitate tracer-to-tracee ratios in plasma were
determined by gas chromatography-mass spectrometry using an MSD 5971 system (Hewlett-Packard, Palo Alto, CA) with a capillary column. An
internal standard ([2-13C]glycerol) was added to each
plasma sample to determine glycerol concentration. 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 anhydride was used to
form a heptafluorobutyric derivative of glycerol, and ions were
produced by electron-impact ionization. Glycerol tracer-to-tracee
ratios were determined by selectively monitoring ions at mass-to-charge
ratios 253, 254, and 257. Free fatty acids (FFA) were isolated from
plasma and converted to their methyl esters. Ions at mass-to-charge
ratios 270.2 and 272.2 produced by electron-impact ionization were
selectively monitored.
Calculations.
Physiological and isotopic steady states were present during the last
15 min of isotope infusion at 14 and 22 h of fasting, so Steele's
equation for steady-state conditions (36) was used to calculate whole
body glycerol, FFA, and NE kinetics.
Subcutaneous ATBF was calculated from 133Xe clearance (20)
where k is the rate constant of the 133Xe
monoexponential washout curve and
is the adipose tissue-to-blood
partition coefficient for 133Xe. The values for k
were determined experimentally as (ln y2
ln y1)/15, where y1 and y2 were the counting rates at
times 0 and 15 min, respectively. The value for
was
assumed to be 10 ml/g (41) for both lean and obese subjects (13).
Subcutaneous adipose tissue plasma flow (ATPF) was calculated as
ATBF · (1-hematocrit).
Net regional release of glycerol and FFA from subcutaneous abdominal
adipose tissue into plasma was quantified by calculating arteriovenous
concentration balance
where [substrate]a and [substrate]v are
either plasma glycerol or FFA arterial and abdominal venous
concentrations, respectively. Glycerol release was calculated using
ATBF, whereas FFA release was calculated using ATPF because of the
absence of FFA in red blood cells.
Adipose tissue NE spillover rate was calculated as
where [NE]v and [NE]a represent venous
and arterial NE concentrations, respectively, and
FexNE is the fractional extraction of NE by adipose
tissue, calculated
as
where SAa and SAv are NE specific activities
in arterial and venous samples, respectively.
Statistical analysis.
Student's t-test for paired samples was used to test the
significance of differences between 14 and 22 h fasting data within lean and obese groups. Student's t-test for independent
samples was used to test for significant differences between lean and obese subjects. One-tailed Student's t-test was used for a
priori comparisons. Pearson product-moment correlation coefficient was computed to determine the relationship between specific variables. A
value of P
0.05 was considered to be statistically
significant. All data are expressed as means ± SE.
 |
RESULTS |
Plasma hormone concentrations.
At 14 h of fasting, plasma insulin concentration was greater
(P < 0.05) in obese than in lean subjects (Table
2). By 22 h of fasting, plasma insulin
concentration declined significantly (P < 0.05) in both
groups, but the percent decline was less in obese than in lean women
(20 ± 3 and 32 ± 5%, respectively; P < 0.05), and
mean plasma insulin concentration remained more than twofold greater in
the obese than in the lean group. Plasma glucagon concentrations were
similar in both groups and increased slightly with continued fasting.
At 14 h of fasting, mean plasma epinephrine concentration in obese
women was about one-half as great as that observed in lean women
(P < 0.05), whereas plasma NE concentrations were similar
in both groups (Table 2). Continued fasting did not cause a significant
change in plasma epinephrine or NE concentrations in either the lean or
obese subjects.
Plasma substrate concentrations.
Abdominal vein plasma glycerol and FFA concentrations were always
greater than arterial concentrations in lean and obese subjects, indicating net glycerol and FFA release from subcutaneous abdominal adipose tissue at both 14 and 22 h of fasting (Table
3). Arterial plasma glycerol and FFA
concentrations increased significantly (P < 0.05) with
continued fasting in both lean and obese subjects.
ATBF.
ATBF was >50% lower in obese compared with lean subjects
(1.84 ± 0.18 and 4.29 ± 0.48 ml · 100 g adipose
tissue
1 · min
1, respectively;
P < 0.05) and did not change between 14 and 22 h of fasting
in either lean or obese subjects.
Substrate kinetics.
At 14 h of fasting, whole body glycerol rate of appearance
(Ra), an index of whole body lipolysis, was greater in
obese than lean women (201.4 ± 17.1 and 123.5 ± 12.3
µmol/min, respectively; P < 0.05; Fig.
2). Whole body FFA Ra, an index
of fatty acid availability in plasma, was also greater in obese than
lean women (526.8 ± 60.6 and 362.2 ± 41.2 µmol/min,
respectively; P < 0.05; Fig. 2). However, glycerol and FFA
kinetics normalized for body fat mass were ~60% lower in obese than
in lean subjects (3.97 ± 0.33 vs. 9.29 ± 1.19 µmol
glycerol · kg fat
mass
1 · min
1 and
10.4 ± 1.2 vs. 26.9 ± 4.5 µmol FFA · kg fat
mass
1 · min
1;
P < 0.05). Continued fasting increased glycerol
Ra and FFA Ra in both lean and obese groups
(Fig. 2). However, the absolute increase in glycerol Ra and
FFA Ra in obese subjects (19.8 ± 7.0 and
87.1 ± 30.3 µmol/min, respectively) was less than the increase observed in lean subjects (44.2 ± 6.6 and 137.4 ± 30.4
µmol/min, respectively; P < 0.05 for both glycerol and
nonesterified fatty acid Ra). The percent increase in
glycerol Ra correlated closely with the percent decline in
plasma insulin concentration in both lean and obese subjects
(r2 = 0.85; P < 0.05; Fig.
3).

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Fig. 2.
Whole body glycerol rate of appearance (Ra; A) and
free fatty acid (FFA) Ra (B) at 14 h (open bars)
and 22 h (hatched bars) of fasting in lean and obese women.
*Significantly different from lean subjects, P < 0.05. Significantly different from 14-h values, P < 0.05. Values are means ±SE.
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Fig. 3.
Relationship between the relative decrease in plasma insulin
concentration and the relative increase in lipolysis (whole body
glycerol Ra) during brief fasting (between 14 and 22 h of
fasting) in lean ( ) and obese ( ) women.
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At 14 h of fasting, net regional glycerol and FFA release from
abdominal subcutaneous adipose tissue in obese subjects were one-half
the value observed in the lean group (Fig.
4), but the difference did not quite reach
statistical significance (P = 0.07) because of the small
number of subjects studied. Between 14 and 22 h, net regional glycerol
and FFA release increased in lean (P < 0.05) but not obese
subjects. Glycerol and FFA release was greater in lean than obese
subjects at 22 h of fasting (P < 0.05; Fig. 4).

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Fig. 4.
Net regional subcutaneous abdominal adipose tissue glycerol
(A) and FFA (B) release at 14 h (open bars) and 22 h (hatched bars) of fasting in lean and obese women. *Significantly
different from lean subjects, P < 0.05. Significantly different from 14-h value, P < 0.05. Values are means ±SE.
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NE kinetics.
Whole body NE spillover in the systemic circulation, a marker of SNS
activity, was similar in both lean and obese groups at 14 h of fasting
(Fig. 5). Fasting caused a significant
decrease in NE spillover in lean but not obese subjects. Regional
abdominal subcutaneous adipose tissue NE spillover, an index of
regional adipose tissue SNS activity, was more than threefold greater
in lean than obese subjects (0.91 ± 0.08 and 0.26 ± 0.06
nmol · 100 g adipose
tissue
1 · min
1, respectively;
P < 0.05). Regional adipose tissue NE spillover did not
change with continued fasting in either lean or obese subjects (Fig.
5).

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Fig. 5.
Whole body (A) and regional subcutaneous abdominal adipose
tissue (B) NE spillover at 14 h (open bars) and 22 h (hatched
bars) of fasting in lean and obese women. *Significantly different from
lean subjects, P < 0.05. Significantly
different from 14-h value, P < 0.05. Values are means
±SE.
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 |
DISCUSSION |
The mobilization of endogenous triglycerides stored in adipose tissue
is important for survival during starvation. In lean men, most of the
increase in whole body lipolytic rates that occur during starvation
takes place within the first 24 h of fasting (19). The results of the
present study demonstrate, for the first time, that the increase in
lipolysis during early starvation (between 14 and 22 h of fasting) is
blunted in women with UBO. However, basal (14-h fast) whole body
lipolytic rates were greater in UBO than lean women and were similar to
values observed in lean women after 22 h of fasting. Therefore, the
attenuated increase in lipolysis during fasting in UBO women did not
compromise fatty acid availability as a fuel in these subjects. In
fact, the blunted lipolytic response in UBO women may be beneficial by
preventing excessive and potentially harmful increases in plasma FFA
concentrations (35, 38).
Our data suggest that the mechanism responsible for differences in the
lipolytic response to fasting in lean and UBO women may be related to
differences in their insulin response. Insulin is a potent inhibitor of
lipolysis in both lean and obese persons (3). Therefore, an alteration
in plasma insulin concentration represents an important adaptive
response to fasting. The decline in plasma insulin observed during
fasting is not simply a response to decreased blood glucose but occurs
even when euglycemia is maintained by exogenous low-dose glucose
infusion (16). In the present study, the relative decrease in plasma
insulin concentration between 14 and 22 h of fasting was smaller in
obese than in lean subjects. In both groups, the relative decrease in
insulin correlated closely with the relative increase in glycerol
Ra, suggesting a causal relationship between changes in
circulating insulin and lipolysis during fasting.
Increased stimulation of adipose tissue
-adrenergic receptors is
another important mechanism for increasing lipolysis during fasting
(18). The increase in
-adrenergic-mediated lipolysis during fasting
is caused, in part, by an increase in adrenal medullary secretion of
epinephrine (27). In the present study, plasma epinephrine
concentration tended to increase between 14 and 22 h but was still
below the threshold level known to stimulate lipolysis (7). However,
fasting increases adipose tissue lipolytic sensitivity to epinephrine
(14, 40), which likely decreases the threshold for
epinephrine-stimulated lipolysis. We have previously found the increase
in lipolysis during epinephrine infusion after short-term fasting is
less in obese than in lean subjects (40). Therefore, altered adipose
tissue sensitivity to epinephrine in our obese subjects may have also
contributed to their blunted lipolytic response to fasting.
This is the first study to evaluate the effects of fasting on adipose
tissue and whole body SNS activity in lean and obese subjects. We used
tracer methodology to measure NE spillover in the systemic circulation
to provide an index of whole body SNS activity (23). Signal
transmission within the SNS involves NE release from sympathetic
postganglionic neurons. Most of the released NE is cleared locally by
neuronal reuptake and effector cell metabolism while a portion spills
over in the bloodstream. Therefore, NE spillover in the systemic
circulation represents NE released from sympathetic neurons distributed
throughout the body and NE secreted from the adrenal medullas. We
combined arteriovenous balance and tracer methodology to determine
regional adipose tissue NE spillover to provide an index of adipose
tissue SNS activity. This approach eliminates any contribution of NE
from the adrenal medullas.
Our results demonstrate that the SNS response to early fasting differs
between lean and obese women. In lean women, whole body NE spillover
declined, but adipose tissue NE spillover did not change between 14 and
22 h of fasting. This heterogeneity may be advantageous by decreasing
SNS activity in lean tissue and thereby decreasing energy expenditure,
while maintaining SNS activity in adipose tissue and thereby
stimulating the mobilization of endogenous triglycerides. These results
are consistent with previous studies that found whole body NE spillover
decreased in lean subjects after 10 days of hypocaloric feeding (26)
and cardiac muscle NE turnover decreased in rats fasted for 48 h (42). In contrast to the lean women, whole body NE spillover rates did not
decrease in obese women during short-term fasting. These results extend
those of Bazelmans et al. (1), who found that 10 days of hypocaloric
feeding did not affect whole body NE spillover in obese subjects.
Therefore, the normal decline in whole body SNS activity that occurs in
response to energy deprivation in lean subjects is blunted in obese
persons. However, adipose tissue SNS activity is maintained during
early starvation in both lean and obese subjects.
Postabsorptive (14-h fast) regional adipose tissue lipolytic rates,
expressed per 100 g of adipose tissue, was 50% lower in our obese than
in our lean subjects. However, the rate of whole body lipolysis was
>60% greater in the obese group because of their large amount of fat
mass; total body fat was more than threefold greater in our obese than
in our lean subjects. Excessive release of FFA in plasma in persons
with UBO may be responsible for several metabolic diseases associated
with obesity by impairing the ability of insulin to stimulate muscle
glucose uptake (6) and suppress hepatic glucose production (6, 15), by
increasing pancreatic insulin secretion (2) and by inhibiting hepatic
insulin clearance (28). Furthermore, increased delivery of FFA to the
liver can increase hepatic very low density lipoprotein production and
plasma triglyceride and cholesterol concentrations (21). The
downregulation of lipolysis per unit of fat mass in obese persons helps
prevent the generation of even greater whole body lipolytic rates.
The marked differences that we observed in regional lipolytic rates
between lean and obese women is inconsistent with the results of a
previous study by Jansson et al. (11), who found the rate of glycerol
release from abdominal subcutaneous adipose tissue was the same in both
lean and obese subjects. It is unlikely that subcutaneous adipose
tissue lipolytic rates were the same in our lean and obese subjects for
several reasons. First, the greater amount of body fat in our obese
subjects would have caused more than a threefold difference in whole
body lipolytic rates between the two groups. Instead, whole body
lipolytic rates were only 60% greater in our obese than in our lean
group. Second, we also found that regional glycerol production measured
by tracer balance methodology (39) gave the same results as the
arteriovenous concentration balance approach (data not shown). Third,
the differences we found in regional glycerol kinetics between lean and
obese subjects were concordant with the differences we found in FFA kinetics. The reason for the discrepancy between the Jansson et al.
(11) study and ours may be related to differences in gender or
methodology. Jansson et al. studied lean and UBO men and measured regional lipolytic activity by using microdialysis probes to sample interstitial adipose tissue glycerol. This latter approach requires an
extrapolation of interstitial glycerol concentration to venous values,
which may generate errors in the estimation of regional glycerol
kinetics. In fact, direct comparisons of the two techniques in the same
subjects have found that regional glycerol output measured by
arteriovenous balance using abdominal vein samples was double the
values obtained by arteriovenous balance using microdialysis samples
(34, 37).
Although we found regional adipose tissue lipolysis in our obese
subjects was one-half the value observed in our lean subjects, in vivo
lipolytic rates per fat cell were probably similar in both groups. Fat
cells from obese persons are larger and contain more lipid than fat
cells from lean persons (11, 29). Subcutaneous abdominal adipocytes
obtained from UBO women with similar body mass index and waist-to-hip
ratio as our subjects have two times the cell volume as adipocytes
obtained from lean women (29). Therefore, our regional measurement of
glycerol and FFA kinetics, which was expressed per 100 g of adipose
tissue, represented glycerol and FFA release from approximately
one-half as many fat cells in the obese than in the lean group. Thus
the rates of glycerol and FFA release per fat cell were similar in both
groups. In contrast, studies performed in vitro have demonstrated that
basal lipolytic rates in isolated adipocytes obtained from UBO women
were threefold greater than lipolytic rates in cells obtained from lean
women (29). However, this discrepancy is probably related to
differences between in vivo and in vitro studies. Other investigators
have also found that lipolysis measured in isolated adipocytes do not agree with in vivo data from the same subjects (22). The differences in
lipolytic activity observed between in vitro and in vivo studies may be
related to alterations in local adipocyte environment caused by removal
of tissue and plasma factors, such as insulin, epinephrine, and adipose
tissue SNS activity.
ATBF, expressed per 100 g of adipose tissue, in our obese subjects was
less than one-half the rate measured in the lean group. The
calculations we used in estimating blood flow assumed that the
partition coefficient for 133Xe is similar in both lean and
obese women (13). Although the lower rate of blood flow in subcutaneous
adipose tissue in obese compared with lean subjects has been observed
previously (11), the mechanism for this phenomenon is not clear but may
be a simple function of the anatomical relationship between capillaries
and adipocytes. Each fat cell is located in proximity to a capillary (5). Blood flow per fat cell remains constant, independent of fat cell
size, so that blood flow per 100 g of adipose tissue decreases with
increasing cell volume (12). It is unlikely that decreased local SNS
was responsible for the lower rate of adipose tissue blood flow even
though subcutaneous fat houses a rich network of blood vessels that
contain vascular
-adrenergic receptors (10). Simonsen et al. (33)
found that
-adrenergic blockade prevented the normal meal-induced
increase in ATBF but did not affect basal blood flow values. Therefore,
adipose tissue SNS innervation may be responsible for the increase in
ATBF after carbohydrate ingestion but does not appear to be an
important regulator of basal, postabsorptive ATBF.
In summary, basal lipolytic rates per unit of fat mass are lower in UBO
women than in lean women, but whole body lipolytic rates are greater in
obese women because of their increased adiposity. During short-term
fasting, whole body lipolytic rates increase in both lean and obese
women, but the increase is blunted in the obese group. This
downregulation of adipose tissue lipolysis in UBO women during fasting
may be advantageous by preventing excessive and potentially harmful
increases in plasma FFA. Our data suggest that the attenuated lipolytic
response to fasting in obese women is related to a blunted decline in
circulating insulin. Altered adipose tissue SNS activity during fasting
does not contribute to the increase in lipolysis in either lean or
obese women. Whole body SNS activity decreased in lean but did not
change in obese women, whereas adipose tissue SNS activity remained the
same during fasting in both groups.
 |
ACKNOWLEDGEMENTS |
We thank Renata Braudy and the nursing staff of the General
Clinical Research Center for help in performing the experimental protocols and Weiqing Feng for technical assistance.
 |
FOOTNOTES |
This study was supported by National Institutes of Health Grants
DK-49989, DK-37948, RR-00036, and RR-00954 and by The Wellcome Trust.
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: S. Klein, Washington University School of
Medicine, 660 S. Euclid Ave., Box 8127, St. Louis, MO 63110-1093.
Received 28 May 1998; accepted in final form 20 October 1998.
 |
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