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PAPER
Increase in plasma pollutant levels in response to
weight loss in humans is related to in vitro
subcutaneous adipocyte basal lipolysis
P Imbeault1, J Chevrier1, É Dewailly1, P Ayotte1, JP Després2,3, A Tremblay1 and P Mauriège1*
1
Department of Social and Preventive Medicine, Laval University, Ste-Foy, Québec, Canada; 2Quebec Heart Institute, Laval
Hospital, Québec, Canada; and 3Lipid Research Center, Laval University Medical Research Center, Québec, Canada
OBJECTIVE: To examine whether weight loss-induced changes in in vitro basal lipolysis of subcutaneous abdominal and femoral
fat cells were related to those in plasma organochlorine levels.
DESIGN: A 15 week weight loss program induced by a moderate caloric restriction.
SUBJECTS: Seventeen men and 20 women (age 36 – 50 y, body fat 25 – 50%).
MEASUREMENTS: In vitro basal lipolysis of subcutaneous abdominal and femoral adipocytes and plasma levels of five
polychlorinated biphenyl congeners (Aroclor 1260, PCBs 118, 138, 153 and 180) and three chlorinated pesticides (dichlor-
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odiphenyl dichloroethene (p,p -DDE), beta-hexachlorocyclohexane (b-HCH) and hexachlorobenzene (HCB)) were measured
before and after the weight reducing program.
RESULTS: Both genders showed a similar reduction in body weight ( 11 kg) in response to treatment, although men lost
significantly more fat mass than women (mean s.d., 9.4 4.1 vs 5.9 5 kg, respectively, P < 0.05). Mean basal fat cell lipolysis
did not vary before and after weight reduction, regardless of depots and genders. In response to weight loss, significant
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increases of all organochlorines investigated were observed in men, whereas only p,p -DDE, Aroclor 1260, PCBs 153 and 180
significantly rose in women. In men, higher the increase in basal lipolysis of subcutaneous abdominal or femoral adipocytes,
greater the rise in plasma levels of most pollutants (HCB, Aroclor 1260, PCBs 118, 138 and 153) was in response to weight loss
(0.51 < r < 0.70, P < 0.05). Similar positive correlations were also observed in women but only a few reached statistical
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significance (p,p -DDE, PCBs 118 and 180).
CONCLUSION: The weight loss-induced increase in plasma pollutant levels is related to the rise in subcutaneous abdominal and
femoral adipocyte basal lipolysis, especially in men.
International Journal of Obesity (2001) 25, 1585 – 1591
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Keywords: organochlorine compounds; PCB; p,p -DDE; reduced-obese
Introduction humans for the most persistent OC.1 OC were used as highly
Quality of life and comfort have considerably increased effective pesticides, dielectrics, fire retardants and were
during the industrialization era for most Western countries. included in ink, plastic and rubber mixtures. Due to their
However, this period of time has also been characterized by lipophilicity, these compounds preferentially bioaccumulate
the production of cheap petrochemical organochlorine com- and biomagnify in higher trophic levels of the food chain.2,3
pounds (OC) displaying high resistance to degradation. Newsome et al4 have previously reported a mean dietary
Biological half-lives of several years have been reported in intake of 5.7 ng polychlorinated biphenyl congeners=kg
body weight=day for Canadians between 1992 and 1996.
Consequently, although the use of these substances has
*Correspondence: P Mauriège, Department of Social and Preventive been banned or restricted in Western countries, they are
Medecine, Division of Kinesiology, Laval University, Ste-Foy, Québec, still found in virtually every person on the planet and
Canada G1K 7P4.
might cause adverse effects in humans.2,5
E-mail: mauriege@club-internet.fr
Received 13 November 2000; revised 21 March 2001; Since pollutants are stored in fat, it has been postulated
accepted 9 May 2001 that adipose tissue loss could result in increased organ and
Adipose tissue lipolysis, weight loss and pollutants
P Imbeault et al
1586
blood concentrations of these compounds.6 A previous study energy expenditure (DEE) of subjects who where sedentary
has confirmed this hypothesis by reporting increased at the onset of the program. To fix energy intake of the
dichlorodiphenyl trichloroethane (DDT)-related compounds weight-reducing program, 700 kcal were subtracted from
concentrations in blood, adipose tissue, heart, lung, spleen DEE.
and brain in starved mice which were a priori treated with a
load of 14C-DDT.7 The impact of body weight loss on plasma
and adipose tissue OC has also been evaluated in humans. Total body fatness and regional fat distribution
Indeed, the concentrations of dichlorodiphenyl dichlor- Body weight was taken with a standard beam scale. Body
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oethene (p,p -DDE) and DDT were found to increase in the density was determined by the underwater weighing techni-
plasma and subcutaneous fat of morbidly obese humans who que and percentage body fat was derived from body den-
were undergoing extensive weight loss in response to an sity.11 Pulmonary residual volume was measured using the
intestinal bypass operation.8 More recently, we have shown helium dilution method.12 Fat mass and fat-free mass were
that a moderate weight loss induced by a caloric restriction derived from the percentage of body fat and total body
of obese subjects was accompanied by a 10 – 29% increase in weight. Computed tomography (CT) was performed with a
plasma and adipose tissue concentrations of detected OC.9 Siemens Somatom DRH scanner (Erlangen, Germany),
We have also reported that, the higher the fat mass loss, the according to the methodology previously described by Sjös-
greater the increase in plasma organochlorine levels in tröm et al.13 Briefly, subjects were examined in the supine
response to the weight loss program. position with both arms stretched above the head. CT scans
Although we suspect that the output of toxic substances were performed both at the abdominal (between L4 and L5
from adipose tissue compartment into the blood stream is vertebrae) and femoral (mid-distance between the knee joint
related to the mobilization of intraadipocyte lipid droplets and the iliac crest) levels, using a scout radiograph to estab-
during caloric restriction, no study has yet verified whether lish the position of the scans to the nearest millimeter. Total
this process is proportional to variation in adipose tissue adipose tissue (AT) areas were calculated by delineating the
lipolytic activity in humans. Therefore, the aim of this study abdomen with a graph pen and then computing AT surfaces
was to verify whether there were relationships between with an attenuation range of 7190 to 730 Hounsfield units
weight loss-induced changes in in vitro basal lipolysis of (HU)14 Abdominal visceral AT area was measured by drawing
subcutaneous abdominal and femoral adipocytes and those a line within the muscle wall surrounding the abdominal
in plasma organochlorine concentrations in a sample of 37 cavity. The abdominal subcutaneous AT area was determined
obese subjects. by subtracting the visceral AT area from the total abdominal
AT area.
Discussion
Results reported in the present study show that changes in
basal lipolysis of subcutaneous abdominal and femoral adi-
pocytes induced by weight loss are related to those in plasma
pollutant levels in men and, to a lesser extent, in women.
Specifically, higher the increase in basal lipolysis of subcuta-
neous abdominal and femoral adipocytes, greater the rise in
plasma OC levels is in response to weight loss.
Because OC are mainly accumulated in fat due to their
lipophilicity,20 it is not surprising to observe an increase in
plasma pollutant levels in response to weight loss. These
Figure 1 Basal lipolysis of subcutaneous abdominal and femoral adipo-
cytes in men and women before and after weight loss. Values are results are consistent with a previous study showing a sig-
means s.e. nificant increase in AT and plasma levels of DDE in eight
Table 3 Relationships between changes (D) in basal lipolysis of and weight gain may be harmful in terms of internal expo-
subcutaneous abdominal and femoral adipocytes and those in plasma sure to toxic substances. Further studies are therefore needed
organochlorine levels of obese men and women in response to weight
loss to address this issue.
The significantly greater increases in plasma OC levels
Men Women after weight loss in men as compared to women could be
D basal lipolysis D basal lipolysis
partly explained by the fact that women lost less body fat
Abdominal Femoral Abdominal Femoral mass than men. As we do not know yet the potential harmful
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effects of a weight loss-increased plasma OC concentrations
D p,p -DDE 0.10 0.19 0.21 0.66{
on human health, sizeable weight and fat losses will have to
D b-HCH 0.44{ 0.04 0.06 0.17
D HCB 0.56* 0.47{ 70.12 0.19 be balanced against the potential hazards of increased OC
D Aroclor 1260 0.67{ 0.53* 0.32 0.32 levels. On the other hand, one could suggest that obesity per
{ {
D PCB 118 0.70 0.60* 0.48* 0.61 se is a major cause for concern since it is associated with
D PCB 138 0.59* 0.52* 0.34 0.34
{ numerous health complications.24 – 26 Accordingly, strategies
D PCB 153 0.68 0.51* 0.25 0.33
D PCB 180 0.46{ 0.32 0.17 0.50* aiming to reduce body weight are obviously relevant to
improve the metabolic risk profile of obese individuals, but
{ {
Statistical significance at: *P < 0.05; P < 0.01; and P ¼ 0.07. should not necessarily attempt to ‘normalize’ body weight.
In this regard, we have recently shown that a physical
activity – low – fat – diet program resulting in a moderate
morbidly obese subjects examined before and 1 y after an body weight loss and a highly favorable improvement of
intestinal bypass operation which resulted in a mean weight the metabolic profile can be achieved in patients still diag-
loss of 47 kg.8 As recently suggested by our group,9 the nosed as overweight27 without inducing additional signifi-
increased plasma OC concentrations of reduced-obese indi- cant increase of their plasma OC levels.9
viduals raise concern about a potentially harmful side effect The similar basal lipolytic rate, regardless of adipose
of weight loss since several pollutants can act as hormone depots or genders, observed in response to weight loss
disrupters.2,5 The clinical significance of the weight loss- appears in contrast with other studies which have shown
induced plasma pollutants levels observed in the present an increase of in vitro basal lipolysis.28 – 31 As recently
study is, however, as yet unknown. On the one hand, the reported by our group32 the discrepancy observed between
effect could be negligible since reduced-obese subjects of the our results and previous data is probably due to the fact that
present study show several times less body burden than that our subjects were biopsied 4 – 6 weeks after the end of the
reported in Inuit adults,21 a population that does not present treatment while they were weight-stable. Within group var-
any greater level of metabolic disease than the Southern iation in basal lipolysis in response to caloric restriction led
Québec population. On the other hand, other studies have us to demonstrate for the first time that higher the increase
shown that PCB levels within the same range as those of the in basal adipocyte lipolysis, greater the rise in plasma OC
present study can alter human thyroid status,22 a gland well levels was. We also showed that these associations were
known for its role in the regulation of energy expenditure. independent of changes in fat mass loss, thus suggesting
Recently, Walford et al23 showed that plasma levels of DDE that there is a direct correlation between the change in basal
and of ‘total PCB’ load increased with weight loss of two crew lipolytic rate of adipocytes and the release of OC from fat to
members sealed inside Biosphere 2, a closed ecological space plasma in response to weight reduction. These significant
of 7 million cubic feet, and then returned to initial values positive relationships between variations in basal AT lipolysis
when their lost weight was restored. Based on this observa- and those in most pollutants investigated were more fre-
tion, it was suggested that alternating periods of weight loss quently observed in men than in women. The reason for this