Meal fatty acid uptake in adipose tissue: gender effects in
nonobese humans
Susan A.
Romanski,
Rita M.
Nelson, and
Michael D.
Jensen
Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota 55905
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ABSTRACT |
We tested for gender differences in dietary fatty acid
metabolism in 12 nonobese men and 12 nonobese women using the meal fatty acid tracer/adipose tissue biopsy study design. In addition to
determining body composition, measurements of regional adipose tissue
lipoprotein lipase activity, blood flow, and fat cell size were
performed to place the meal fatty acid kinetic studies in perspective.
Twenty-four hours after ingesting the test meal, the concentration of
meal fatty acids was greater (P < 0.05) in abdominal
subcutaneous than in thigh adipose tissue in both men (0.61 ± 0.12 vs. 0.45 ± 0.09 mg/g) and women (0.59 ± 0.10 vs. 0.43 ± 0.05) but was not different between men and women. A
greater percentage of dietary fat was stored in subcutaneous adipose
tissue in women than in men (38 ± 3 vs. 24 ± 3%,
respectively, P < 0.05), and a greater portion of meal
fatty acid disposal was unaccounted for in men. Significant gender
differences in regional adipose tissue blood flow after meal ingestion
were noted; the differences were in the direction that could support
greater nutrient storage in lower body fat in women.
[14C]triolein; body composition; visceral fat; adipose tissue blood flow
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INTRODUCTION |
NORMAL-WEIGHT ADULT
MEN and women have remarkably different body composition. Women
have more body fat, a greater proportion of fat in their lower body,
and much less visceral fat than men do at the same body mass index. The
reasons for these differences in body fat distribution have not been
clearly identified but are potentially important. If these same
processes determine body fat distribution as obesity develops,
understanding the factors regulating body fat distribution in men vs.
women could help us understand upper-body vs. lower-body obesity.
Regional differences in lipolysis (27) and/or triglyceride
(TG) storage capacity (23) have been proposed as
determining regional fat accumulation. In vitro studies of adipocytes
obtained from different regions have suggested that both mechanisms may
be operative (23, 27). We have looked for
variations in regional lipolysis in vivo (10, 12, 21) but have been unable to document
important gender differences in this regard. Thus studies of adipose
tissue fatty acid uptake would seem appropriate.
The approach of Björntorp et al. (1) and Marin and
colleagues (16-19) to study fatty acid uptake in
human adipose tissue in vivo appears promising. The meal fatty acid
tracer/adipose tissue biopsy technique involves administering a
radiolabeled fatty acid tracer together with a fat-containing meal,
followed some time later by adipose tissue biopsies from different
regions to assess the relative efficiency of meal fatty acid uptake.
Marin and co-workers (17, 19) reported that
meal fatty acids are more concentrated in upper body subcutaneous than
in lower body subcutaneous adipose tissue in women (19)
and in men (17). Direct comparisons of meal fatty acid
uptake in adipose tissue between men and women have not been made,
however. Thus it is unknown whether the relative difference in the
ability of adipose tissue to concentrate meal fatty acids is different
between lower body and upper body adipose tissue in men and in women.
Likewise, it is unknown whether women oxidize a different proportion of meal fatty acids than men, which could perhaps lead to greater net fat
accumulation. The present studies were designed to address these issues
and to examine whether there were physiological correlates of regional
meal fat storage in nonobese men and women. We examined whether
regional differences in fat cell size, lipoprotein lipase (LPL)
activity, or adipose tissue blood flow were related to the regional
meal fatty acid uptake.
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METHODS AND MATERIALS |
Subjects.
Written, informed consent was obtained from 24 nonobese, healthy
volunteers (12 males and 12 premenopausal females). The subjects were
taking no medications, including oral contraceptives. All volunteers
were weight stable (<1.0 kg weight variation) for at least 2 mo before
the study. The women were studied in the follicular phase of their
menstrual cycle. These are the same subjects and the same experiments
described in the previous companion report (24).
Materials.
L-[14C]triolein (Du Pont NEN Research
Products) and [3H]triolein (American Radiolabel Chemical,
St. Louis, MO) were sonicated into a liquid meal. 133Xe
(Syncor, St. Paul, MN) was dissolved in sterile saline and was used to
measure regional adipose tissue blood flow.
Assays and methods.
Fat cell size was assessed using the approach of Di Girolamo et al.
(3). Oxygen consumption and carbon dioxide expiration were
measured by indirect calorimetry using a DeltaTrac Metabolic Cart
(Yorba Linda, CA). Volunteers were acclimatized to the hood for the
first 10 min of each 30-min measurement. The basal metabolic rate
measurements were made at 0700, after a 12-h overnight fast, before the
volunteer had arisen from bed. Urinary nitrogen was measured using an
Analox GM7 Fast Enzymatic Metabolite Analyzer (Analox Instruments,
Lunenburg, MA). Plasma glucose concentrations were measured with a
Beckman glucose analyzer (Beckman Instruments, Fullerton, CA). Plasma
insulin concentrations were measured using a chemiluminescence method
with the Access Ultrasensitive Immunoenzymatic assay system (Beckman,
Chaska, MN). A modified Pasteur pipette was used to aspirate the
chylomicron layer that had been separated from 2.0 ml of fresh plasma
by ultracentrifugation at 780,000 g/min in a 50.3 Ti rotor
(Beckman Instruments, Spinco Division, Palo Alto, CA). The TG
concentrations were measured on a small portion of the sample
(9), and the remainder of the sample was subjected to a
Dole extraction (4) to measure chylomicron TG
radioactivity. Adipose tissue and meal lipids were extracted using
standard (5) procedures, and the TG SA was measured as previously described (19). The meal aliquots were
subjected to serial dilution to be able to compare the ratio of
3H to 14C at the same level of radioactivity in
adipose tissue and meal.
Adipose tissue heparin-releasable LPL activity was measured using the
approach of Nilsson-Ehle and Schotz (22). Body fat and
fat-free mass (FFM) was measured using dual-energy X-ray absorptiometry (DEXA; DPX-IQ; Lunar Radiation, Madison, WI; see Ref. 14). Thigh adipose tissue and muscle areas were measured using a single-slice computed tomography (CT) at the mid-thigh level;
intra-abdominal and abdominal subcutaneous fat areas were measured at
the L2-3 level by a single-slice CT scan
(13). Total body water was measured with
2H2O (26). The triolein tracers
were assayed for radiochemical purity by measuring the radioactivity in
the TG and non-TG fractions by HPLC (2). To assess the
proportion of radioactivity present in oleate, the TG fraction was
subjected to alkaline hydrolysis followed by conversion to a phenacyl
derivative and injection on a second HPLC (20). The non-TG
fraction (nonesterified fatty acids) was also derivatized and assayed
for purity by HPLC (20).
Protocol.
The volunteers underwent all body composition measurements before the
adipose tissue biopsy study. A complete blood count, chemistry group,
and lipid profile were documented to be within normal limits before the
study. All female volunteers had a negative pregnancy test before
participating in the study. Subjects consumed all of their meals in the
General Clinical Research Center (GCRC) for 1 wk before the study to
ensure consistent macronutrient intake (50% carbohydrate, 35% fat,
and 15% protein). They were instructed not to eat anything except what
was provided for them through the study, and food intake was adjusted
if necessary to maintain a stable weight. Each volunteer's energy
requirement was estimated using the Harris-Benedict formula
(8) and usual daily activity. The macronutrient intake the
week before the tracer study for the men and women, respectively, was
as follows: energy intake 2,952 ± 64 and 2,114 ± 62 kcal/day; protein intake 115 ± 3 and 84 ± 3 g/day;
carbohydrate intake 379 ± 9 and 271 ± 8 g/day (53 ± 3% simple carbohydrate); fat intake 118 ± 3 and 83 ± 3 g/day (37 ± 2% saturated fat).
The volunteers were admitted to the Mayo Clinic GCRC the evening before
the study. The morning of the study after an overnight fast, a catheter
was placed in a forearm vein and was used to collect blood samples.
Before the administration of the experimental meal, baseline breath and
urine samples were collected for measurement of
14CO2 (7) and
3H2O (11) specific activity (SA).
Approximately 90 min before the morning test meal, injections of 0.15 mCi of 133Xe were administered (15) in the
abdominal subcutaneous and thigh subcutaneous adipose tissue beds. A
1-ml U-100 insulin syringe with a 25-gauge needle was used. The
abdominal injection was given just lateral and inferior to the
umbilicus at the site of the most abundant subcutaneous fat. The thigh
injection was given in the anterior thigh at the junction of the upper
one-third and the lower two-thirds of the distance between the hip and
the knee. Each injection was given in the middle of the subcutaneous
fat. The fluid was injected slowly (over 1 min), and the needle was not
removed for an additional 30 s to prevent reflux of
133Xe along the needle track. A 16 × 2-mm collimated
solid-state cadmium telluride detector (RMD, Watertown, MA) that has a
96% counting efficiency for 133Xe was positioned over each
injection site and held in place with adhesive tape. A pulse height
analyzer (Tennelec T246) was set to count only those pulses that
corresponded to the energy level of 133Xe (81 keV) and to
discriminate against background noise and scattered radiation outside
the selected energy range (75-200 keV). A count rate meter
(Tennelec T593) was used to average the number of counts over 1-s time
intervals, and the results were recorded on a two-channel strip chart
recorder (HP 7132A). Each channel recorded the counts from its
respective injection site. Measurements were made from the time of the
injection until 1 h after the midday meal to allow calculation of
subcutaneous adipose tissue blood flow during fasting and after the
morning and the midday meals.
At 0800, the volunteers consumed a meal providing 40% of their resting
energy needs as determined by indirect calorimetry, providing 692 ± 22 and 509 ± 15 kcal for men and women, respectively. The meal
consisted of a liquid formula (Ensure Plus, Ross Laboratories) containing 57% carbohydrate, 27% fat (16% saturated fat, 27%
monounsaturated fat, 57% polyunsaturated fat), and 15% protein to
which 20 µCi of L-[14C]triolein and 40 µCi of [3H]triolein had been added. The volunteers were
also provided with solid food meals at 1300 and 1800 that provided the
remainder of their usual daily energy intake and contained the same
portion of nutrients as the diets provided during the week before the study. The volunteers remained seated or lying in bed during the first
8 h after consuming the test meal except as needed to void. After
8 h, the volunteers were allowed to walk around the room or the
GCRC. Because the intravenous saline infusion was continued to maintain
venous access, the physical activity of the volunteers was necessarily limited.
To determine the exact amount of
L-[14C]triolein and
[3H]triolein consumed, quadruplicate 50-µl samples
of the meal were counted using dual-channel liquid scintillation
counting. The meal was weighed to the nearest milligram. Aliquots of
the meal were also saved for measurement of meal lipid 14C
and 3H SA (see above).
After consuming the test meal, blood and breath samples were obtained
hourly for 8 h, every 2 h for an additional 4 h, and then every 4 h until the next morning. The blood samples were analyzed for plasma chylomicron TG and nonchylomicron TG 3H
and 14C SA, as well as for plasma glucose and insulin
concentrations. Breath samples were collected as described above to
measure expired 14CO2 SA. Indirect calorimetry
was performed hourly beginning at 0800 for 8 h and at the 10th
hour with the volunteers lying quietly in bed. Urine was collected for
24 h after the test meal to assess 3H2O
losses and concentration as well as nitrogen excretion.
Twenty-four hours after the test meal consumption, adipose tissue
biopsies were obtained using the sterile technique under local
anesthesia. Biopsies were taken from the left and right abdominal
subcutaneous, gluteal, and thigh regions. The lipid was extracted from
the tissues, accurately weighed, and counted on the scintillation
counter to <2% counting error. The adipose tissue TG (3H
and 14C; dpm/mg lipid) was calculated for each site.
Adipose tissue LPL activity and fat cell size were measured on one side
(either right or left) at each site. After the adipose tissue biopsies, the intravenous catheter was removed, and the volunteers ate breakfast and were dismissed.
Calculations.
Meal fatty acid oxidation for the 24 h after the test meal was
calculated using both the 3H and 14C tracers.
The production of 3H2O was calculated by
multiplying the concentration of 3H2O in body
water (using a urine sample obtained 24 h after the test meal) by
total body water as measured by the 2H2O space
and adding the 3H2O lost in the urine over the
24 h. This value (total 3H2O dpm produced)
was divided by the total [3H]triolein consumed to
calculate the fraction of meal fatty acids oxidized in the first
24 h after the meal.
As noted in the companion report (24), two volunteers had
previously participated in studies involving the infusion of
[3H]palmitate, which rendered their 3H
adipose tissue data unusable. Because there was no
3H2O in the baseline urine samples of these two
volunteers, the 3H2O generation values were
used to calculate meal fatty acid oxidation.
The production of 14CO2 was determined by
multiplying the 14CO2 SA by the CO2
production rate, as measured by indirect calorimetry, at each time
point. The nocturnal CO2 production rate time points were
not measured in this study, although the 14CO2
SA was. To estimate the nocturnal CO2 production rates at the nocturnal time points, we used data from a previous study (25) to develop a nonlinear model that predicts
CO2 production throughout the night using the 1800 and 0800 O2 consumption and CO2 production rates. This
model predicted ~75% of the variance in CO2 production
rates of an independent sample. To calculate meal fatty acid oxidation
using [14C]triolein, the area under the
14CO2 curve was divided by the amount of
[14C]triolein consumed.
To calculate adipose tissue blood flow (ATBF), the 10-min slope index
was used according to the following equation
where 2.3 is the factor for converting common to natural
logarithms, l is the partition coefficient for adipose
tissue, and d is the numerical value of the slope in the
semilog (base 10) system. The value used for the partition coefficient
is 10 (15).
Oxygen consumption and CO2 production (l/min) and urinary
nitrogen excretion (g nitrogen/min) were used to calculate carbohydrate and fat oxidation rates (6). An area under the curve
(trapezoidal rule) calculation was used to assess carbohydrate and
fatty acid oxidation over the first 5 h after the experimental meal.
Meal fatty acid uptake in adipose tissue was calculated as follows. The
adipose tissue TG SA (dpm/g) was divided by the meal TG SA (dpm/mg) to
predict the meal TG fatty acid uptake (mg meal TG/g adipose tissue TG).
The average of values obtained using both the 3H and
14C tracers was used for these calculations except for the
two volunteers who had previously received a 3H fatty
tracer (see Ref. 24), in whom only the 14C values were
considered. Visceral fat mass was predicted using the CT measures of
intra-abdominal and subcutaneous adipose tissue combined with
DEXA-measured abdominal fat as previously described (13).
Upper body subcutaneous fat was taken as upper body fat (DEXA) minus
visceral fat, and leg fat was measured using DEXA. The average of both
sides of the site-specific concentration of meal TG per gram in adipose
tissue TG was multiplied by the TG mass to estimate total meal TG
uptake in the different adipose tissue depots, similar to the approach
of Marin et al. (19).
Statistics.
All values are presented as means ± SE. Comparisons of baseline
characteristics between men and women were performed using a nonpaired
t-test. Testing for differences between adipose tissue sites
and between men and women (e.g., LPL activity or fat cell size) was
done using a 2 (gender) × 3 (site) repeated-measures ANOVA.
Testing for differences in adipose tissue blood flow over time, between
thigh and abdominal sites in men and women, was assessed using a 2 (gender) × 2 (site) × 5 (time) repeated-measures ANOVA with
the factors of site and time as repeated measures. Post hoc testing was
performed using paired or nonpaired t-tests as appropriate.
Comparison of plasma TG concentration data was done using
log-transformed values because of the skewed distribution. Univariate
linear regression analysis was used to test for associations between
fat cell size, adipose tissue LPL activity, and adipose tissue blood
flow (independent variables) and relative meal fatty acid uptake in
adipose tissue. The relative meal fatty acid uptake was examined as
absolute uptake (mg meal fat/g adipose tissue fat) and as the
proportion of meal fatty acids stored in lower body and upper body
subcutaneous adipose tissue.
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RESULTS |
Subject characteristics.
The men and women participating in this study were well matched for age
and body mass index. As expected, men were heavier, with a lesser
percentage of body fat and more visceral fat than women. Thigh skeletal
muscle area by CT was significantly greater in men than in women,
whereas thigh adipose area was less in men. The total amount of leg fat
was not statistically significantly less (P = 0.11) in
men than in women; however, the percent of body fat present as leg fat
was greater in women than men (42 ± 1 vs. 37 ± 1%,
respectively, P < 0.05). The estimated amount of
visceral fat in men and women was 1.41 ± 0.17 and 0.77 ± 0.12 kg, respectively (P < 0.005). Upper body
subcutaneous fat was calculated to be 7.7 ± 0.8 and 8.4 ± 0.9 kg in men and women [P = not significant (NS)],
respectively (Table 1).
There was a significant (P = 0.002) site difference in
adipocyte diameter and a significant gender effect (P = 0.02). Gluteal and thigh adipocytes were significantly larger in women
than in men; however, abdominal adipocyte diameter was not
significantly different between groups. In addition, gluteal and thigh
adipocytes were significantly larger than abdominal adipocytes in
women, whereas no site differences were found in men.
The LPL activity (µmol free fatty acid released · h
1 · mg tissue
1) in abdominal,
gluteal, and thigh adipose tissue in women was 0.24 ± 0.03, 0.32 ± 0.06, and 0.44 ± 0.06, respectively, and in men it
was 0.19 ± 0.04, 0.23 ± 0.04, and 0.31 ± 0.08. A
significant (P = 0.03) site difference (greater LPL
activity in thigh than abdominal adipose tissue) was noted, but no site
by gender effect was present (P = 0.75).
Glucose, insulin, and TG responses.
The plasma glucose and insulin concentration responses during the
experimental day were virtually the same in men and women (Fig.
1). Plasma chylomicron TG concentrations
and nonchylomicron TG concentrations are depicted in Fig.
2. No gender differences in plasma
chylomicron TG concentrations were found. There was a trend
(P = 0.06) for average nonchylomicron TG concentrations to be greater in men than in women.

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Fig. 1.
Plasma insulin (A) and glucose (B)
responses throughout the day depicted for the 12 men and 12 women
participating in this study.
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Fig. 2.
Plasma chylomicron triglyceride (TG) concentrations
(B) and nonchylomicron TG concentrations (A) in
the 12 men and 12 women participating in this study.
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Energy metabolism.
Resting O2 consumption was 188 ± 5 and 251 ± 10 ml/min in men and women, respectively, and the overnight postabsorptive
respiratory quotient was 0.77 ± 0.01 and 0.80 ± 0.02 (P = NS) in men and women.
The total amount of carbohydrate oxidized during the 5 h after the
experimental meal was 2.7 ± 0.3 and 3.3 ± 0.3 kcal/kg FFM in men and women, respectively (P = NS). Total fatty
acid oxidation over the same time interval was 3.4 ± 0.4 and
3.4 ± 0.2 kcal/kg FFM in men and women, respectively
(P = NS). As assessed by 24-h 14CO2 excretion, men and women oxidized 21 ± 2 and 22 ± 1% of meal fatty acids (P = NS),
whereas by 3H2O generation, 28 ± 1 and
32 ± 2% of meal fatty acids were oxidized the day after
consumption of the experimental meal (P = NS, men vs. women).
Regional adipose tissue blood flow.
Adipose tissue blood flow in the abdomen and thigh for men and women is
depicted in Fig. 3. Baseline
(prebreakfast) blood flow in the abdominal (1.9 ± 0.4 and
2.2 ± 0.4 ml · 100 ml
tissue
1 · min
1 in men and women,
respectively) and thigh (2.3 ± 0.5 and 1.5 ± 0.2 ml · 100 ml tissue
1 · min
1
in men and women, respectively) depots was not different in men vs.
women or between sites. A significant (P < 0.0001)
time effect was noted in abdominal adipose tissue blood flow
(midmorning greater than baseline), and a trend was noted for a
time-by-gender interaction [P = 0.03 by multilinear
ANOVA (MANOVA), P = 0.06 for univariate ANOVA]. Post hoc analyses did not uncover significant
differences in abdominal adipose tissue blood flow between men and
women; however, the increase in abdominal blood flow after lunch was significant (P < 0.005) in men but not in women.
Likewise, a significant (P < 0.02) time effect was
noted in thigh adipose tissue blood flow, and a trend for a gender
interaction (P = 0.08 by MANOVA, P = 0.002 for univariate ANOVA) was present. The time of the differences is
noted in Fig. 3. Thigh adipose tissue blood flow in women in the
midmorning was 7.2 ± 1.4 ml · 100 ml
tissue
1 · min
1 and after lunch was
5.4 ± 1.1 ml · 100 ml tissue
1 · min
1.

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Fig. 3.
Adipose tissue blood flow in the thigh (A) and
abdominal (B) area in the 12 men and 12 women participating
in this study. * P < 0.01 vs. men.
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Regional meal fatty acid uptake.
The experimental meal contained 24.6 ± 0.8 and 18.1 ± 0.5 g of TG for men and women, respectively. The relative uptake
of meal fatty acids in abdominal, gluteal, and thigh adipose tissue for
men and women is depicted in Fig. 4. The
meal fatty acid uptake in abdominal (0.61 ± 0.12 and 0.59 ± 0.10 mg meal fat/g adipose tissue lipid), gluteal (0.59 ± 0.11 and 0.53 ± 0.11), and thigh (0.45 ± 0.09 and 0.43 ± 0.05) adipose tissue was not different between men and women,
respectively, as indicated by the lack of a significant site by gender
effect. A significant (P = 0.005) site effect was
present, however. The concentration of meal fatty acids was
significantly greater in abdominal fat than in thigh fat
(P < 0.05), whereas the uptake in gluteal fat was not
significantly different from abdominal or thigh sites.

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Fig. 4.
Uptake of meal fatty acids in abdominal, gluteal, and
thigh adipose tissue in men and women 24 h after the ingestion of
an experimental meal. No statistically significant between-group
differences were found. * P < 0.05 vs. abdomen.
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The concentration of meal fatty acids per gram adipose tissue lipid in
abdominal fat was multiplied by the amount of subcutaneous upper body
adipose tissue to estimate the storage of meal fat in this depot. A
similar approach was used to estimate the uptake of meal fat in leg
adipose tissue using the concentration of meal fatty acid in thigh
adipose tissue. The percentage of meal fatty acids stored in upper body
subcutaneous adipose tissue and in leg adipose tissue was greater
(P < 0.05) in women than in men (Fig.
5A). The sum of meal fatty
acid uptake in leg and upper body subcutaneous adipose tissue (total
subcutaneous) plus meal fatty acids oxidized over 24 h (using the
3H2O method) is shown in Fig. 5B. A
greater portion of dietary fat was stored in subcutaneous adipose
tissue in women than in men (38 ± 3 vs. 24 ± 3%,
respectively, P < 0.05). Because the percentage of
meal fatty acids oxidized was not different in women and men (see
above), this indicated that the percent of fatty acids that we could
not account for was greater (P < 0.005) in men than
women (45 ± 4 vs. 30 ± 3%, respectively).

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Fig. 5.
A: concentration of meal fatty acids in
adipose tissue was multiplied by regional adipose tissue mass to
determine total meal fatty acid uptake in upper body and lower body
adipose tissue in men and women. Data are expressed as a percentage of
the total meal fatty acids ingested. B: proportion of meal
fatty acids stored in total subcutaneous adipose tissue, oxidized, or
unaccounted for (missing) 24 h after the ingestion of the meal.
* P < 0.05 vs. women; P = 0.06 vs. women (see text for further analysis).
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Relationships between fat cell size, LPL activity, adipose blood
flow, and lipid uptake.
No statistically significant correlations were found between fat cell
size or adipose tissue LPL activity and the absolute or relative
quantities of meal fatty acids stored in the different adipose tissue
depots in men or women. Within individuals, the greatest relative
uptake of meal fatty acid was in the abdomen (70% of volunteers) and
gluteal (30% of volunteers) sites, whereas thigh LPL activity was
greater than other sites in 67% of volunteers.
We examined the relationship between the average adipose tissue blood
flow from the midmorning measurement through the postlunch interval and
the percentage of meal fatty acids stored in the corresponding depots
in men and women (Figs. 6 and
7). The only statistically significant
relationship was that between meal fatty acid uptake in leg fat and
average thigh adipose tissue blood flow in women.

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Fig. 6.
Percentage of meal fatty acids stored in the lower body (thigh)
plotted vs. the average thigh adipose tissue blood flow during the day
for women (A) and men (B).
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Fig. 7.
Percentage of meal fatty acids stored in the abdomen plotted vs.
the average abdomen adipose tissue blood flow during the day for women
(A) and men (B).
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DISCUSSION |
These studies were designed to test for differences in
meal-related fatty acid metabolism between nonobese men and women. We
also wished to determine whether any differences that might be present
would be consistent with the differences in body fat distribution. To
assure comparable conditions in men and women, we controlled the diet
at isoenergetic levels for 1 wk before the study and designed the
experimental meal test day such that it would be a comparable
physiological challenge for both groups. The test meal provided 40% of
resting energy needs as measured by indirect calorimetry, and its fat
content was comparable to a usual meal. The plasma glucose, insulin,
and chylomicron responses during the test day were quite similar in men
and women. In addition, substrate oxidation and meal fatty acid
oxidation were not different. We found that the concentration of meal
fatty acids was greater in abdominal subcutaneous fat than in thigh
adipose tissue in both men and women, implying preferential uptake in
upper body fat. The main gender difference was that women stored a
greater percentage of dietary fat in subcutaneous adipose tissue than did men. In addition, we noted significant gender differences in
regional adipose tissue blood flow after meal ingestion, which was in
the direction that might indicate a relationship to regional fat storage.
Meal fatty acid oxidation for the 24 h after the ingestion of the
experimental meal was not different in men and women. Meal fatty acid
disposal in subcutaneous adipose tissue was estimated by multiplying
the regional adipose tissue concentration of meal fatty acids by
appropriate subcutaneous adipose tissue mass for each individual. After
accounting for meal fatty acid oxidation and uptake in subcutaneous
adipose tissue, some dietary fatty acids could not be accounted for.
This proportion was significantly greater in men than in women.
Considering the more avid uptake of meal fatty acids in intra-abdominal
adipose tissue than in subcutaneous adipose tissue previously reported
by Marin et al. (16), it is possible that the
"missing" meal fatty acids were stored in this depot. Indeed, a
positive correlation was noted between the percentage of meal fatty
acids that were missing and visceral fat mass (Fig.
8). The experimental design that we
employed does not allow us to discern whether the differences in meal
fat uptake in subcutaneous fat between men and women create the
differences in body composition between men and women or are due to the
differences in body composition. Additional experiments will be needed
to address these possibilities.

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Fig. 8.
Visceral fat mass plotted vs. the percentage of meal fat
that was unaccounted for (not oxidized, nonsteroidal subcutaneous fat)
24 h after meal ingestion. Open and closed symbols represent
values from female and male volunteers, respectively. One of the open
symbols is obscured by a closed symbol. Circles represent values from
individuals who received the first (less pure) lot of
[3H]triolein, and squares represent values from
individuals who received the second lot of
[3H]triolein.
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As noted in the companion report (24), the first lot of
[3H]triolein used in these studies was less pure (~82%
oleate) than the second lot (>90% pure). Differences in tracer purity
affected the ability to directly compare adipose tissue fatty acid
uptake using the two different tracers. These differences did not,
however, affect the relationship between the two isotopic measures of
meal fatty acid oxidation (24) or the relationship between
"missing" meal fat and visceral fat (Fig. 8). We conclude that any
skewing of results that occurred due to the ~10% difference in
tracer purity between the two [3H]triolein lots did not
materially affect the cross-sectional usefulness of the data. This
likely reflects the fact that the majority of the purity differences
were in long-chain unsaturated fatty acids that would be expected to
have a metabolic fate similar to oleate.
We could not find previous reports of regional differences in adipose
tissue blood flow in men and women after mixed meal ingestion. The
observation that thigh adipose tissue blood flow increased more in the
postprandial period in women than in men is of interest; greater blood
flow could deliver more chylomicrons to leg adipose tissue in women,
potentially increasing the opportunity for additional fat storage. A
tendency was noted for the proportion of dietary fatty acids stored in
abdominal and thigh adipose tissue to relate to blood flow to that
region (Figs. 4 and 5). These trends are of interest and, if confirmed
in future studies, may indicate that blood flow to adipose tissue in
the postprandial period is one of the regulators of regional meal fatty
acid storage.
Consistent with a previous report (19), we could not
detect a significant association between adipose tissue LPL activity and meal fatty acid storage. We acknowledge, however, that the LPL
activity was measured in the postabsorptive state, whereas the majority
of clearance of meal fatty acids occurred in the initial 2-12 h
after meal ingestion (24). Sampling adipose tissue at the
time of maximum clearance of dietary fatty acids may allow one to
better detect a relationship between LPL activity and the relative
uptake of meal fatty acids in adipose tissue.
Of interest, the concentration of meal fatty acids in gluteal adipose
tissue was intermediate between that of abdominal adipose tissue and
thigh adipose tissue in both men and women. Thus gluteal adipose tissue
may not be entirely representative of lower body/leg adipose tissue.
Some investigators use gluteal adipose tissue as a representative site
for lower body, whereas others use thigh adipose tissue. If meal fatty
acid uptake can be used as a distinguishing marker for regional
differences in adipose tissue fatty acid metabolism, our results
suggest that thigh adipose tissue is the preferred site for comparisons
with upper body subcutaneous adipose tissue.
In summary, these studies have examined the fate of dietary fatty acids
in nonobese men and women. We found that men and women oxidized
comparable proportions of dietary fat but that a greater fraction of
dietary fat was stored in subcutaneous adipose tissue in women than in
men. The relationship between the missing dietary fat and visceral fat
mass (Fig. 8) leads us to suspect that those fatty acids we could not
account for by subcutaneous adipose tissue storage or oxidation are
taken up by visceral fat. Men and women had regional differences in
adipose tissue blood flow during the day. The observed differences were
in the direction that would support greater nutrient deposition in
lower body fat in women. Regulation of postprandial adipose tissue
blood flow could be another mechanism by which dietary fat is directed
toward one adipose tissue depot compared with another. Future studies
will be needed to address this possibility.
 |
ACKNOWLEDGEMENTS |
We acknowledge the technical assistance of Joan Aikens and Carol
Siverling, the staff of the Mayo Clinic General Clinical Research
Center, and Susan Leachman for editorial assistance.
 |
FOOTNOTES |
This work was supported by National Institutes of Health Grants
DK-45343, DK-50456 (Minnesota Obesity Center), and RR-0585, and by the
Mayo Foundation.
Address for reprint requests and other correspondence: M. D. Jensen, Endocrine Research Unit, 5-194 Joseph, Mayo Clinic,
Rochester, MN 55905 (E-mail: jensen.michael{at}mayo.edu).
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.
Received 24 August 1999; accepted in final form 13 March 2000.
 |
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