The transient Stephen
hypercholesterolemia
D Phinney,
ABSTRACT
adipose during
Anna
Serum
cholesterol and after
(VLCDs).
B Tang,
of5.49
and
± 0.32
2 mo ofVLCDs
Rita
studied diets
started
at
to 3.62
(nadir),
body
Waggoner,
composition,
Subjects
lipoproteins,
R
contents of six obese women were major weight loss by very-low-calorie 168
lost 30.3 ± 3.7 kg in 5-7 mo, maintenance. Serum cholesterol value
Carolyn
of major weight
± 1 1% of ideal
followed by 2+ mo fell from a predict
± 0.31
mmol/L
which
it rose
after
body
(P to 5.95
in weight (baseline)
cholesterol
± 0.36
1-
content
biopsy sites with weight sociated
but
did rose
loss.
with
not
change
significantly
that
rise in serum
bilization of adipose weight loss ceased.
KEY WORDS adipose cholesterol
major
and
adipose
weight possibly
stores,
which resolved 199 1;53: 1404-10.
J C/in Nutr
Very-low-calorie
diets,
leg) tissue
from
serum
mo-
this
(14).
This
variability
lost,
etiology
and
of this
patients mo,
VLCDS
evidence
linked
on this information, dertaken combined
that
reduction
to a reduction
the National
cholesterol
risk
Institutes
in the
appropriate
of Health
therapeutic 5. 1 7 mmol/L
steps
serum concentrations > (5). The first therapeutic step recommended patient with hypercholesterolemia (defined is a diet
to normalize
body
weight
(6).
the weight-loss
regimen
is a progressive
lesterol
as the
person’s
excess
relation
between
is well-established
excess
weight
for
result
in serum Although
elevated
(7), the mechanism
un-
to intervene
expected
is lost.
and
have
screening, and the gen-
reduction
weight
for
>
rise
predict
weight
body
composition
after
88%
and
of 44
from
weight
they
cholesterol serum,
six moderately
loss induced
in a multidisciplinary
2
serum
while
we obtained
data
major
had
of serum loss,
of adult
within
36% values
the dynamics major
and
mmol/L,
above
during
during
that
is the
course
fall in cholesterol
0.5
>
In the
outpatient
by a weight-
clinic.
chocor-
cholesterol
for a relationship
methods
Subjects This
outpatient
volunteers response
between
bles
study
aged
(15)].
Predict and
studies
to exclude
the
y who
month
from
studies cardiac,
All subjects beginning
for
All were
included blood
six obese
recruited
[IBW; taken as the from the Metropolitan
routine
before
data were
advertisements.
weight range
diogram, dysfunction.
comprises
27-42
to newspaper
of ideal body medium-frame of
the
serum
and
act
for the overweight as > 5. 17 mmol/L)
The
explained. in serum cholesterol 3 mo.
of
underlying
been
observed
rise
administered
Subjects
(3, 4). To
a campaign to promote serum cholesterol with a major effort to educate physicians
ci-al public
we
amount
but the
and obesity (1, 2). There
in serum
in coronary
composition,
a diet-induced a late
and
management
reasonable
taken
concentrations
women
VLCD
is directly
arc
research,
tissue,
not
studied
in methodology
acquisition,
variability
total
cholesterol
groups
to differences
loss
serum
(HDL)
as diet
has
intriguing
its subfractions
obese
is now
ofsample
showed
adipose
serum cholesterol concentration risk factors for atherosclerosis
such
timing
weight
in all patient
be due
studies,
experienced
73%
and
Introduction Both elevated are well-established
could
outpatient
to reduce
response
variability
A particularly rise seen when
Although
shown
high-density-lipoprotein
a uniform
these
weight
(10-12). was
were still losing weight. To explore more carefully
cholesterol,
A Davis
(VLCDs)
raise
is not
cholesterol
when
Paul
or exercise
and
(13),
other
loss was as-
cholesterol,
cholesterol
Am
(arm
in abdominal
We conclude
a late
in peripheral
diets
dieting
between
mmol/
P < 0.01 compared with nadir and baseline) as weight loss continued. With weight maintenance, serum cholesterol fell to 4.92 ± 0.34 mmol/L (P < 0.05 compared with peak). Adipose L (peak,
cholesterol
very-low-calorie by either
after
and
vation (9). Further, a tendency for a late rise in serum cholesterol was observed in patients undergoing therapeutic weight loss with
weight,
0.01)
6 mo),
on an outpatient
by intermittent food weight-loss protocol, formed,
protocol
for both
(17). were
was obtained
quested ing the
LOSS
intake
protocol Human
loss, ofthe
intake
or fatigue Subjects
Diets
Because
WEIGHT
up to a total
of the subjects did not of the six subjects com-
in Table 1 . The study of California at Davis
pleting the protocol are included was approved by the University Subjects Committee, from each subject
pool
two
DURING
Age
Height
Weight
y
cm
kg
%
Percent
BMI
IBWt
At C
loss
At D
Maximum
kg
1
Opti
41
41.5
43.2
27
115.5 83.5
41.9
MFP
166 163
203
2
152
31.4
31.9
29.6
38.0
3
Opti
32
168
104.2
180
36.9
22.2
19.9
22.2
4
Opti
39
168
114.1
197
40.4
31.4
27.5
31.4
5
Opti
41
170
88.8
148
30.7
22.5
22.0
22.5
6
MFP
42
163
80.3
146
30.2
21.3
19.0
21.8
37
166
97.7
168
35.2
28.5
26.9
30.3
3.0
3.4
3.7
.;
SEM *
Opti,
2 Optifast
70, Sandoz,
t Ideal body weight (15). Body mass index (weight
§ Point
C, point
of maximum
1
Minneapolis. in kg divided late
rise
5.8
MFP,
meat-fish-poultry
by height
in meters
in cholesterol;
point
11
2. 1
VLCD. squared).
D, weight
Downloaded from https://academic.oup.com/ajcn/article-abstract/53/6/1404/4732435 by guest on 31 March 2018
stability
after
refeeding
to calorie
maintenance.
45.7
1406
PHINNEY
ET
AL
culated according to the Friedewald formula with 0.20 used for the ratio ofcholcsterol to TG in VLDL (19). All determinations were done in duplicate. Serum apolipoproteins A-I and B (apo A-I and apo B) were quantitated by radioimmunoassay (RIA; Ventrex Labs, Portland, ME). The apo A-I RIA method utilized a monoclonal antibody and radiolabeled apo A-I. The apo B RIA employed a polyclonal antibody and radiolabeled LDL. All samples were run in duplicate and the apolipoprotcin concentrations were calculated from standard curves fitted by logistic-regression analysis. Adipose-tissue cholesterol analysis. Subcutaneous adipose tissue was obtained from three body sites (triceps, abdomen, and
tests
quadriceps-lateral
serum
samples,
panel
shows
thigh)
then
twice during
22-35
kg loss.
14-gauge
needle,
analysis.
After
weight The
by
biopsy
loss: after
tissue
was
washing,
before
dieting
12-1 5 kg loss and again
obtained
on saline,
floated careful
needle
via
and
suction
stored
was
after
through
at -20
10 mg tissue
and a
#{176}C until
digested
in
1
mL 20 g KOH/L ethanol-water (9: 1, by vol) containing 20 g of 5-13-cholcstan-3a-ol. The capped tube was incubated in a 70 #{176}C water bath for 90 mm. Two milliliters hexane and 1 mL water were then added, mixed thoroughly, and centrifuged for 10 mm at 500 X g, after which 0.6 mL ofthe hexanc phase was removed and blown to dryness under nitrogen gas, mixed with 0.1 mL silylating mixture [4 vol BSTFA (Sigma, St Louis) and 5 vol dry pyridinc] and incubated in a capped tube for 60 mm at 37 #{176}C. The samples were analyzed by gas chromatography on an HP 5890
instrument
equipped
with
an UItra-l
l2.5-m
capillary
shown
the
from
the ratio
cholesterol
content
of the internal
of the
tissue
was
with
authentic
or multiple samples adipose tissue). The
TO and cholesterol ±10% (n = 5).
derived procedure
of 95% (n
=
from
in the
caloric
merged
subjects
was
obtained
for a 3-5
s interval
after
Statistical
Data
‘;
!
on a microcomputer
(2 1). The
results
the PC-SAS
for the
serum
figure
shows
the
weights
calculated
60
40 20 0
35 Cl)
fully
sub-
(I)
maximal 15
10 5 0
by using
in this
100
40
analysis
was performed
al-
120
of
residual
analysis
hypo-
140
(pig of
lung volume was measured concurrently by nitrogen washout. This procedure was repeated several times until three consistent weights were obtained. The Siri equation was used for the calculation of percent body fat (20). The
the weights,
subjects’
panel
20
exhalation.
with
subjects’
as percent loss from initial weight and illustrates the remarkably similar responses of these subjects to the two VLCDS in the outpatient setting. Presented in this way, the data indicate both the uniformity ofweight loss among subjects and also the quality of adherence to the diets by the individual subjects. This figure also shows the different durations ofthe VLCDS (some subjects
overnight
the
starting
0. The
lower
25
for
values
at month
80
a reproducibility
reading
of weekly
parallel lines for the first 4 weight-loss regimens. The
.
weight
plot
beginning
though different at the start, follow mo when all subjects were prescribed
0 _I
A continuous
by using
figures.
the
diets
Body-composition analysis. Body fat content was quantitated by densitometry three times for each subject at the same times that adipose biopsies were done. All studies were done after an fast.
done
completed the full protocol including repeated adipose biopsies, and body-composition studies. Two ofthesc were assigned the food VLCD and four, the formula VCLD. These subjects’ weights arc shown in Figure 1. The upper
standards.
a single tissue showed a recovery
6) and
were
calculated
The TG content of the tissue was determined by measuring the glycerol content ofthe adipose digestion aqueous layer with a commercial assay kit for TO (Gilford GPO triglyceride). The aqueous phase volume was quantitated and a sample was analyzed as described above for serum TG analysis. Data for recovery and reproducibility of the TO and cholesterol values were determined by using known lipid mixtures (Sigma) omental
times
col-
standard to the cholesterol peak. Both peaks and their relative
Each sample was run in triplicate. response factors were established
between
Six subjects
(Hewlett-Packard, Palo Alto, CA) run at 275 #{176}C with a split ratio of 100: 1 with helium carrier and a flame-ionization detector. Output data were integrated with an HP 3396A reand
differences
Results
umn
corder,
for individual
the least-significant-differences test. The threshold for significance was taken as P < 0.05. Data in the text and tables are expressed as the mean ± SEM. For comparisons ofserum samples chosen at selected times (A, baseline; B, nadir; C, peak total cholesterol late in weight loss; D, maintenance), the absolute values were used for statistical analysis rather than the normalized values
package lipoprotein
fractions, adipose cholesterol content, and body composition were assessed over time by analysis of variance (ANOVA), and
Downloaded from https://academic.oup.com/ajcn/article-abstract/53/6/1404/4732435 by guest on 31 March 2018
0
1
2
3
4
5
6
7
8
9
10
Month FIG 1. Weight loss for six subjects as kilogram over time and as percent weight lost. Month 0 begins with the start ofweight-loss dieting.
HYPERCHOLESTEROLEMIA chose
to continue
1 provides
initial
weight
loss after
weight,
height,
the six subjects completing weights at which the peak cholesterol (At of serum-chemistry or kidney
or mineral
loss or maintenance
this
of the three
initial
the
monthly
six subjects. were below
value
all subjects
and
the
showed
refeeding
1 and
the
total
either
be seen
serum
magnitude same
the basis in liver
of the
pattern
of an
initial
a decline
By comparing
all subjects
by month
panel
with
calories.
had
Figures
experienced
4, at which
ofFigure
to
rise as the weight weight stabilization
time
a rise
1 show continued
uniform
showed regardless
the same pattern ofserum cholesterol changes of VLCD used. However, the sample size
(two
VLCD,
four
ifthere
formula
was a difference
between
the two diets.
response
pattern
subsequent
among
data
Thus,
VLCD)
in the magnitude
because
all subjects
are grouped
was too small
to deter-
ofthcse
changes
of the uniformity and
the
small
independently
ofthe
of the
sample VLCD
the duration of the VLCD varied for subjects, dietchanges in serum lipids could not be compared on an absolute time scale. To normalize the data for the various periods of dieting, four serum cholesterol values were selected for each the initial 1-2 of the
phase
C.)
50
200
-
0 4)
150
U) 4)
0
100
.c C.)
50
-J
0 I
0-
150 0
(C),
preweight VLCD (B),
and
loss level (A), the peak value
the maintenance
value
100
U)
4) 0
.c C.)
50
-J
0 -I
0
FIG 3. Serum total, HDL, and taken for each subject at baseline total cholesterol peak (C), and in values are normalized as percent
once
weight
loss had
time
was lower
value
at A for
panel
of Figure
absolute
values),
These
data
3. By repeated-measures the
changes
in serum
are
in the
top
The
ANOVA
(using
the
from the maintenance
total
cholesterol
over
8.0
serum
the serum
LDL,
6.0
P
subject’s
their than
4.0
initial The
ended
subjects
after
weight
The 0.35,
0 7
0123456
were
8
9
10
Month FIG 2. Serum total cholesterol, monthly values for each subject. The dotted line at 5.17 mmol/L represents the acceptable upper limit according to current guidelines (6).
Downloaded from https://academic.oup.com/ajcn/article-abstract/53/6/1404/4732435 by guest on 31 March 2018
had lower loss
ratios 0.26,
also
above) time
HDL
the
or C (P
there
final
it to LDL
that
as adults. tissue
close
subjects’ after
in weight redistributes
interpretation
However,
± SEM.
showed
in individuals
subjects’ and
relinquish
period of an atherogenic basis this could measurably
The
FIG 5. Cholesterol-triglyceride ratio (expressed in moles) from adiposetissue biopsies. Samples were taken at baseline and after 12-15 and 22-
slowly
et al (39)
occurred
fluctuations weight loss
temporary recurring
C.)
then
could lead to a prolonged elevation in serum over time and thus more risk of cholesterol
in other tissues. In this context, it is interesting to 25-y follow-up of the Western Electric Study partici-
0
.c
I 409
LOSS
as
of peripheral
Downloaded from https://academic.oup.com/ajcn/article-abstract/53/6/1404/4732435 by guest on 31 March 2018
5.
Lipid
Kris-Etherton
lesterol
PM,
Education
Krummel
Program:
D, Russell
the effect
ME,
et al. National
of diet on plasma
Cho-
lipids,
Ii-
1410 poproteins,
and coronary
heart
disease.
J Am Diet
Assoc
PHINNEY
ET
l988;88:
23.
Sorbris R, Petersson BG, Nilsson-Ehle P. Effects ofweight reduction on plasma lipoproteins and adipose tissue metabolism in obese subjects. Eur J Clin Invest l98l;l 1:49 1-8.
24.
Follick
1373-98.
6. The Expert Panel. Report of the National Cholesterol Education Program Expert Panel on detection, evaluation, and treatment of high
cholesterol
in adults.
Arch
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7. Glueck CK, Taylor HL, Jacobs D, Morrison JA, Beaglehole R, Wilhams OD. Plasma high density lipoprotein cholesterol: association with measurements of body mass; the Lipid Research Clinics Programs Prevalence Study. Circulation l980;62(suppl IV):62-9. 8. Lissner L, Habicht J-P, Strupp BJ, Levitsky DA, Haas JD, Roe DA. Body composition and energy intake: do overweight women overeat and underreport? Am J Clin Nutr l989;49:320-5. 9. Ende N. Serum cholesterol in acute starvation: a report of 20 cases.
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Body composition from fluid spaces and density-analysis ofmethods. In: Brozek J, Henschel A, eds. Techniques for measuring body composition. Washington, DC: National Academy of Sciences Siri WE.
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2 1 . SAS Institute, Inc. SAS guide for personal computers, version 6 edition. Cary, NC:SAS Institute Inc. 1985. 22. Weisweiler P. Plasma lipoproteins and lipase and lecithin: cholesterol acyltransferase activities in obese subjects before and after weight reduction. J Clin Endocrinol Metab 1987;65:969-73.
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DB,
Smith
TW,
Henderson
HJ. Metabolic aspects of acute starvation Am J Clin Nutr l967;20:672-83.
1983;2:123-32.
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1 1. Bistrian BR, Blackburn GL, Flatt J-P, Sizer J, Scrimshaw NS, Sherman M. Nitrogen metabolism and insulin requirements in obese diabetic adults on a protein sparing modified fast. Diabetes l987;25: 494-504. 12. Anderson JW, Ngai B, Hamilton C, Riddlemoser M, Crown-Weber E. Serum lipid responses of obese men and women to very lowcalorie diets. Clin Res l988;36:753(abstr). 13. Wood PD, Stefanick ML, Dreon DM, et al. Changes in plasma lipids and lipoproteins in overweight men during weight loss through dieting as compared with exercise. N Engl J Med l988;3 19: 1173-9. 14. Thompson PD, Jeffrey RW, Wing RR, Wood PD. Unexpected decrease in plasma high density lipoprotein cholesterol with weight loss. Am J Clin Nutr 1979;32:20l6-21. 15. Society ofActuaries. Build and blood pressure study. Vols I and II. Chicago: Society ofActuaries, 1959. 16. National Research Council. Recommended dietary allowance& 10th
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Contrasting short- and long-term effects ofweight loss on lipoprotein levels. Arch Intern Med 1984; 144:1571-4. 25. Schwartz RS, Brunzell JD. Increase of adipose tissue lipoprotein lipase activity with weight loss. J Clin Invest 198 1;67: 1425-30. 26. Consolazio CF, Matoush LO, Johnson HL, Nelson RA, Krzywicki
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Eckel RH. Adipose tissue lipoprotein lipase. In: Borensztajn J, ed. Lipoprotein lipase Chicago: Evener, 1987:79-132. Phinney SD, Horton ES, Sims EAH, Hanson JS, Danforth E Jr, LaGrange BM. Capacity for moderate exercise in obese subjects afteradaptation to a hypocaloric ketogenic diet. J Clin Invest 1980;66: 1152-61. Phinney
SD,
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Wadden
their
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safety,
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Brownell
and future.
Ann
KD.
Intern
Very-low-calorie
Med
diets:
1983;99:675-84.
hypercholesterolemia
D Phinney,
ABSTRACT
adipose during
Anna
Serum
cholesterol and after
(VLCDs).
B Tang,
of5.49
and
± 0.32
2 mo ofVLCDs
Rita
studied diets
started
at
to 3.62
(nadir),
body
Waggoner,
composition,
Subjects
lipoproteins,
R
contents of six obese women were major weight loss by very-low-calorie 168
lost 30.3 ± 3.7 kg in 5-7 mo, maintenance. Serum cholesterol value
Carolyn
of major weight
± 1 1% of ideal
followed by 2+ mo fell from a predict
± 0.31
mmol/L
which
it rose
after
body
(P to 5.95
in weight (baseline)
cholesterol
± 0.36
1-
content
biopsy sites with weight sociated
but
did rose
loss.
with
not
change
significantly
that
rise in serum
bilization of adipose weight loss ceased.
KEY WORDS adipose cholesterol
major
and
adipose
weight possibly
stores,
which resolved 199 1;53: 1404-10.
J C/in Nutr
Very-low-calorie
diets,
leg) tissue
from
serum
mo-
this
(14).
This
variability
lost,
etiology
and
of this
patients mo,
VLCDS
evidence
linked
on this information, dertaken combined
that
reduction
to a reduction
the National
cholesterol
risk
Institutes
in the
appropriate
of Health
therapeutic 5. 1 7 mmol/L
steps
serum concentrations > (5). The first therapeutic step recommended patient with hypercholesterolemia (defined is a diet
to normalize
body
weight
(6).
the weight-loss
regimen
is a progressive
lesterol
as the
person’s
excess
relation
between
is well-established
excess
weight
for
result
in serum Although
elevated
(7), the mechanism
un-
to intervene
expected
is lost.
and
have
screening, and the gen-
reduction
weight
for
>
rise
predict
weight
body
composition
after
88%
and
of 44
from
weight
they
cholesterol serum,
six moderately
loss induced
in a multidisciplinary
2
serum
while
we obtained
data
major
had
of serum loss,
of adult
within
36% values
the dynamics major
and
mmol/L,
above
during
during
that
is the
course
fall in cholesterol
0.5
>
In the
outpatient
by a weight-
clinic.
chocor-
cholesterol
for a relationship
methods
Subjects This
outpatient
volunteers response
between
bles
study
aged
(15)].
Predict and
studies
to exclude
the
y who
month
from
studies cardiac,
All subjects beginning
for
All were
included blood
six obese
recruited
[IBW; taken as the from the Metropolitan
routine
before
data were
advertisements.
weight range
diogram, dysfunction.
comprises
27-42
to newspaper
of ideal body medium-frame of
the
serum
and
act
for the overweight as > 5. 17 mmol/L)
The
explained. in serum cholesterol 3 mo.
of
underlying
been
observed
rise
administered
Subjects
(3, 4). To
a campaign to promote serum cholesterol with a major effort to educate physicians
ci-al public
we
amount
but the
and obesity (1, 2). There
in serum
in coronary
composition,
a diet-induced a late
and
management
reasonable
taken
concentrations
women
VLCD
is directly
arc
research,
tissue,
not
studied
in methodology
acquisition,
variability
total
cholesterol
groups
to differences
loss
serum
(HDL)
as diet
has
intriguing
its subfractions
obese
is now
ofsample
showed
adipose
serum cholesterol concentration risk factors for atherosclerosis
such
timing
weight
in all patient
be due
studies,
experienced
73%
and
Introduction Both elevated are well-established
could
outpatient
to reduce
response
variability
A particularly rise seen when
Although
shown
high-density-lipoprotein
a uniform
these
weight
(10-12). was
were still losing weight. To explore more carefully
cholesterol,
A Davis
(VLCDs)
raise
is not
cholesterol
when
Paul
or exercise
and
(13),
other
loss was as-
cholesterol,
cholesterol
Am
(arm
in abdominal
We conclude
a late
in peripheral
diets
dieting
between
mmol/
P < 0.01 compared with nadir and baseline) as weight loss continued. With weight maintenance, serum cholesterol fell to 4.92 ± 0.34 mmol/L (P < 0.05 compared with peak). Adipose L (peak,
cholesterol
very-low-calorie by either
after
and
vation (9). Further, a tendency for a late rise in serum cholesterol was observed in patients undergoing therapeutic weight loss with
weight,
0.01)
6 mo),
on an outpatient
by intermittent food weight-loss protocol, formed,
protocol
for both
(17). were
was obtained
quested ing the
LOSS
intake
protocol Human
loss, ofthe
intake
or fatigue Subjects
Diets
Because
WEIGHT
up to a total
of the subjects did not of the six subjects com-
in Table 1 . The study of California at Davis
pleting the protocol are included was approved by the University Subjects Committee, from each subject
pool
two
DURING
Age
Height
Weight
y
cm
kg
%
Percent
BMI
IBWt
At C
loss
At D
Maximum
kg
1
Opti
41
41.5
43.2
27
115.5 83.5
41.9
MFP
166 163
203
2
152
31.4
31.9
29.6
38.0
3
Opti
32
168
104.2
180
36.9
22.2
19.9
22.2
4
Opti
39
168
114.1
197
40.4
31.4
27.5
31.4
5
Opti
41
170
88.8
148
30.7
22.5
22.0
22.5
6
MFP
42
163
80.3
146
30.2
21.3
19.0
21.8
37
166
97.7
168
35.2
28.5
26.9
30.3
3.0
3.4
3.7
.;
SEM *
Opti,
2 Optifast
70, Sandoz,
t Ideal body weight (15). Body mass index (weight
§ Point
C, point
of maximum
1
Minneapolis. in kg divided late
rise
5.8
MFP,
meat-fish-poultry
by height
in meters
in cholesterol;
point
11
2. 1
VLCD. squared).
D, weight
Downloaded from https://academic.oup.com/ajcn/article-abstract/53/6/1404/4732435 by guest on 31 March 2018
stability
after
refeeding
to calorie
maintenance.
45.7
1406
PHINNEY
ET
AL
culated according to the Friedewald formula with 0.20 used for the ratio ofcholcsterol to TG in VLDL (19). All determinations were done in duplicate. Serum apolipoproteins A-I and B (apo A-I and apo B) were quantitated by radioimmunoassay (RIA; Ventrex Labs, Portland, ME). The apo A-I RIA method utilized a monoclonal antibody and radiolabeled apo A-I. The apo B RIA employed a polyclonal antibody and radiolabeled LDL. All samples were run in duplicate and the apolipoprotcin concentrations were calculated from standard curves fitted by logistic-regression analysis. Adipose-tissue cholesterol analysis. Subcutaneous adipose tissue was obtained from three body sites (triceps, abdomen, and
tests
quadriceps-lateral
serum
samples,
panel
shows
thigh)
then
twice during
22-35
kg loss.
14-gauge
needle,
analysis.
After
weight The
by
biopsy
loss: after
tissue
was
washing,
before
dieting
12-1 5 kg loss and again
obtained
on saline,
floated careful
needle
via
and
suction
stored
was
after
through
at -20
10 mg tissue
and a
#{176}C until
digested
in
1
mL 20 g KOH/L ethanol-water (9: 1, by vol) containing 20 g of 5-13-cholcstan-3a-ol. The capped tube was incubated in a 70 #{176}C water bath for 90 mm. Two milliliters hexane and 1 mL water were then added, mixed thoroughly, and centrifuged for 10 mm at 500 X g, after which 0.6 mL ofthe hexanc phase was removed and blown to dryness under nitrogen gas, mixed with 0.1 mL silylating mixture [4 vol BSTFA (Sigma, St Louis) and 5 vol dry pyridinc] and incubated in a capped tube for 60 mm at 37 #{176}C. The samples were analyzed by gas chromatography on an HP 5890
instrument
equipped
with
an UItra-l
l2.5-m
capillary
shown
the
from
the ratio
cholesterol
content
of the internal
of the
tissue
was
with
authentic
or multiple samples adipose tissue). The
TO and cholesterol ±10% (n = 5).
derived procedure
of 95% (n
=
from
in the
caloric
merged
subjects
was
obtained
for a 3-5
s interval
after
Statistical
Data
‘;
!
on a microcomputer
(2 1). The
results
the PC-SAS
for the
serum
figure
shows
the
weights
calculated
60
40 20 0
35 Cl)
fully
sub-
(I)
maximal 15
10 5 0
by using
in this
100
40
analysis
was performed
al-
120
of
residual
analysis
hypo-
140
(pig of
lung volume was measured concurrently by nitrogen washout. This procedure was repeated several times until three consistent weights were obtained. The Siri equation was used for the calculation of percent body fat (20). The
the weights,
subjects’
panel
20
exhalation.
with
subjects’
as percent loss from initial weight and illustrates the remarkably similar responses of these subjects to the two VLCDS in the outpatient setting. Presented in this way, the data indicate both the uniformity ofweight loss among subjects and also the quality of adherence to the diets by the individual subjects. This figure also shows the different durations ofthe VLCDS (some subjects
overnight
the
starting
0. The
lower
25
for
values
at month
80
a reproducibility
reading
of weekly
parallel lines for the first 4 weight-loss regimens. The
.
weight
plot
beginning
though different at the start, follow mo when all subjects were prescribed
0 _I
A continuous
by using
figures.
the
diets
Body-composition analysis. Body fat content was quantitated by densitometry three times for each subject at the same times that adipose biopsies were done. All studies were done after an fast.
done
completed the full protocol including repeated adipose biopsies, and body-composition studies. Two ofthesc were assigned the food VLCD and four, the formula VCLD. These subjects’ weights arc shown in Figure 1. The upper
standards.
a single tissue showed a recovery
6) and
were
calculated
The TG content of the tissue was determined by measuring the glycerol content ofthe adipose digestion aqueous layer with a commercial assay kit for TO (Gilford GPO triglyceride). The aqueous phase volume was quantitated and a sample was analyzed as described above for serum TG analysis. Data for recovery and reproducibility of the TO and cholesterol values were determined by using known lipid mixtures (Sigma) omental
times
col-
standard to the cholesterol peak. Both peaks and their relative
Each sample was run in triplicate. response factors were established
between
Six subjects
(Hewlett-Packard, Palo Alto, CA) run at 275 #{176}C with a split ratio of 100: 1 with helium carrier and a flame-ionization detector. Output data were integrated with an HP 3396A reand
differences
Results
umn
corder,
for individual
the least-significant-differences test. The threshold for significance was taken as P < 0.05. Data in the text and tables are expressed as the mean ± SEM. For comparisons ofserum samples chosen at selected times (A, baseline; B, nadir; C, peak total cholesterol late in weight loss; D, maintenance), the absolute values were used for statistical analysis rather than the normalized values
package lipoprotein
fractions, adipose cholesterol content, and body composition were assessed over time by analysis of variance (ANOVA), and
Downloaded from https://academic.oup.com/ajcn/article-abstract/53/6/1404/4732435 by guest on 31 March 2018
0
1
2
3
4
5
6
7
8
9
10
Month FIG 1. Weight loss for six subjects as kilogram over time and as percent weight lost. Month 0 begins with the start ofweight-loss dieting.
HYPERCHOLESTEROLEMIA chose
to continue
1 provides
initial
weight
loss after
weight,
height,
the six subjects completing weights at which the peak cholesterol (At of serum-chemistry or kidney
or mineral
loss or maintenance
this
of the three
initial
the
monthly
six subjects. were below
value
all subjects
and
the
showed
refeeding
1 and
the
total
either
be seen
serum
magnitude same
the basis in liver
of the
pattern
of an
initial
a decline
By comparing
all subjects
by month
panel
with
calories.
had
Figures
experienced
4, at which
ofFigure
to
rise as the weight weight stabilization
time
a rise
1 show continued
uniform
showed regardless
the same pattern ofserum cholesterol changes of VLCD used. However, the sample size
(two
VLCD,
four
ifthere
formula
was a difference
between
the two diets.
response
pattern
subsequent
among
data
Thus,
VLCD)
in the magnitude
because
all subjects
are grouped
was too small
to deter-
ofthcse
changes
of the uniformity and
the
small
independently
ofthe
of the
sample VLCD
the duration of the VLCD varied for subjects, dietchanges in serum lipids could not be compared on an absolute time scale. To normalize the data for the various periods of dieting, four serum cholesterol values were selected for each the initial 1-2 of the
phase
C.)
50
200
-
0 4)
150
U) 4)
0
100
.c C.)
50
-J
0 I
0-
150 0
(C),
preweight VLCD (B),
and
loss level (A), the peak value
the maintenance
value
100
U)
4) 0
.c C.)
50
-J
0 -I
0
FIG 3. Serum total, HDL, and taken for each subject at baseline total cholesterol peak (C), and in values are normalized as percent
once
weight
loss had
time
was lower
value
at A for
panel
of Figure
absolute
values),
These
data
3. By repeated-measures the
changes
in serum
are
in the
top
The
ANOVA
(using
the
from the maintenance
total
cholesterol
over
8.0
serum
the serum
LDL,
6.0
P
subject’s
their than
4.0
initial The
ended
subjects
after
weight
The 0.35,
0 7
0123456
were
8
9
10
Month FIG 2. Serum total cholesterol, monthly values for each subject. The dotted line at 5.17 mmol/L represents the acceptable upper limit according to current guidelines (6).
Downloaded from https://academic.oup.com/ajcn/article-abstract/53/6/1404/4732435 by guest on 31 March 2018
had lower loss
ratios 0.26,
also
above) time
HDL
the
or C (P
there
final
it to LDL
that
as adults. tissue
close
subjects’ after
in weight redistributes
interpretation
However,
± SEM.
showed
in individuals
subjects’ and
relinquish
period of an atherogenic basis this could measurably
The
FIG 5. Cholesterol-triglyceride ratio (expressed in moles) from adiposetissue biopsies. Samples were taken at baseline and after 12-15 and 22-
slowly
et al (39)
occurred
fluctuations weight loss
temporary recurring
C.)
then
could lead to a prolonged elevation in serum over time and thus more risk of cholesterol
in other tissues. In this context, it is interesting to 25-y follow-up of the Western Electric Study partici-
0
.c
I 409
LOSS
as
of peripheral
Downloaded from https://academic.oup.com/ajcn/article-abstract/53/6/1404/4732435 by guest on 31 March 2018
5.
Lipid
Kris-Etherton
lesterol
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