¹School of Human Kinetics, University of Ottawa, Ottawa, Ontario, Canada

²Division of Kinesiology, Laval University, Ste-Foy, Québec, Canada

³Department of Food Science and Nutrition, Laval University, Ste-Foy, Québec, Canada

Correspondence to: A Tremblay, Division of Kinesiology, Laval University, Ste-Foy, Québec, Canada G1K 7P4. E-mail: angelo.tremblay@kin.msp.ulaval.ca

Guarantor: A Tremblay.

Contributors: ED carried out the field work, analysed the data and wrote the paper. SS-P carried out the field work. NA was involved in the concept and planning and carried out the field work. PI carried out the field work and analysed the data. PM analysed the data. AP carried out the field work. J-PD was involved in the concept and planning. AT was involved in the concept and planning and wrote the paper.

Objective: The aims of the present study were to retrospectively: (1) compare how weight loss affects the reduction of adipose tissue from three different sites between men and women; and (2) to verify whether gender differences in the reduction of adipose tissue are influenced by changes in fat mass (FM) and initial levels of fat in different compartments.

Design: Double-blind randomized treatment with fenfluramine once daily coupled to a non-macronutrient specific energy restriction.

Subjects: Seventeen obese men (age 43.9±1.5 and body mass index (BMI) 34.3±0.7) and 17 obese women (age 41.2±1.2 and BMI 35.7±0.6).

Interventions: Subjects were given fenfluramine (60 mg) or placebo once daily and were also subjected to a non-macronurient specific energy restriction of -2.9 MJ/day (-700 kcal/day) for 15 weeks.

Results: Body weight, FM, fat-free mass (FFM), waist circumference, BMI, as well as visceral (VAT), subcutaneous abdominal (SAT) and thigh (TAT) adipose tissue were all significantly reduced. Men lost significantly more VAT (-41.6%) than SAT (-22.5%), or than TAT (-20.5%) while no site difference in fat loss was observed in women when changes were calculated as a percentage of initial levels. Men lost about twice as much fat from the VAT compartment than did women (P<0.05), even after having considered changes in FM as a potential covariate. In absolute values, TAT was reduced to a lesser extent in men than in women. However, when initial levels of respective fat depots were also taken into account, gender differences in VAT and TAT loss were no longer statistically significant.

Conclusion: These results suggest that gender differences in VAT reduction during weight loss are independent of changes in FM. However, once initial levels of VAT are also taken into account, gender differences in the reduction of this tissue during weight loss are no longer apparent.

European Journal of Clinical Nutrition (2002) 56, 297-304. DOI: 10.1038/sj/ejcn/1601334

weight loss; preferential fat reduction; visceral adipose tissue

Introduction

With recent technological advancements, particularly related to computed tomography (CT), magnetic resonance imaging (MRI) and ultrasonography, clinical trials have been conducted to address with more accuracy how weight loss affects different adipose depots. Accordingly, a recent review of the literature has shown that, as a proportion of initial levels, more visceral adipose tissue (VAT) is lost when compared to the relative decrease in total body adiposity, irrespective of the mode of intervention used to induce weight loss (Smith & Zachwieja, 1999). Generally speaking, when calculated as a percentage of initial levels about one-third to half more fat is lost from VAT than from the abdominal subcutaneous adipose tissue (SAT) compartment in response to weight loss interventions (Fujioka et al, 1991; Goodpaster et al, 1999; Gray et al, 1991; Ross et al, 1996b; Stallone et al, 1991; Zamboni et al, 1993). Since VAT is characterized by a greater lipolytic capacity and a lesser antilipolytic action of insulin than SAT, or adipose tissue from the mid-thigh (TAT) region (Hellmer et al, 1992; Leibel & Hirsch, 1987; Mauriège et al, 1995), it is not surprising that, during weight loss, VAT would be more readily reduced. Moreover, it has also been reported that a lesser decrease in VAT is observed in women than in men in response to weight loss (Goodpaster et al, 1999; Wirth & Steinmetz, 1998). Since large initial levels of VAT seem to be associated with the reduction of fat from this compartment during weight loss (Fujioka et al, 1991; Marks et al, 1996,1998), these gender differences in VAT reduction are possibly attributable to higher initial levels of VAT in men. Accordingly, it has been recently demonstrated that, when pre-treatment VAT levels are taken into account, no difference in the reduction of fat from this compartment in response to weight loss could be observed between men and women (Janssen & Ross, 1999).

Apart from the fact that initial levels of VAT are generally higher in men, another difference is also quite often observed during weight loss and that is the fact that women generally lose less of their initial body fat than men even after a comparable weight loss. Moreover, since women display a greater initial adiposity and since reductions in specific adipose tissue compartments are also quite closely related to the reduction in total adiposity, it seems relevant to address whether or not gender differences in VAT reduction during weight loss are also independent of changes in fat mass (FM).

This study was thus performed retrospectively to clarify the distribution pattern of weight loss from three different adipose tissue compartments, ie VAT, SAT and TAT as determined by CT in response to a 15 week energy restriction, in men and women. More particularly, we wanted: (1) to compare how weight loss affects the reduction of adipose tissue from three different sites within and between genders; (2) to verify whether gender differences in site reduction are independent of changes in FM; and (3) to also assess if the relation between the reduction of fat from VAT, SAT and TAT is affected by the initial levels of these variables. A secondary objective of this study was to examine clinical predictors of changes in VAT, SAT and TAT.

Methods

Since the main objectives of this study were related to the reduction of adipose tissue from three different sites, subjects who lost less than 5% of their initial body weight (six women (four fenfluramine and two placebos) and two men (two fenfluramine)) were excluded from the present study. Thus, from 42 subjects (19 men and 23 premenopausal women) who had completed 15 weeks of drug or placebo therapy-energy restriction intervention and in whom all variables were available, 34 (17 men and 17 premenopausal women) were included to test the main hypotheses in the present study. This study was double-blind and subjects were given a number in the order in which they were recruited for the study. Drug or placebo had already been randomly assigned to these numbers while respecting the ratio of 5:1 drug- to placebo-treated individual. Subjects were either given fenfluramine (60 mg) or a placebo once daily for the duration of the program (men=12 and five and women=14 and three drug and placebo treated, respectively). This pharmacological approach to treat obesity was coupled with a non-macronutrient specific energy restriction which corresponded to a reduction of energy intake of 2.9 MJ/day (700 kcal/day). The non-macronutrient specific energy-restricted diet was fixed with a resting metabolic rate (RMR) measurement to which an activity factor of 1.4 was multiplied to estimate daily energy expenditure (daily energy expenditure=resting metabolic rate (kcal/min)´1440 min/day´1.4) of subjects who were sedentary at the onset of the program. To fix the energy intake of the intervention, 2.9 MJ (700 kcal) were subtracted from daily energy expenditure (estimated from the RMR measurement). A 3 day dietary record was also used in order to assess macronutrient intake of subjects. The dietary records were analyzed with a computerized version of the Canadian Nutrient File (1991) in order to maintain the initial macronutrient composition throughout the intervention. In order to achieve the energy restriction and to maintain initial macronutrient composition, the food exchange system from the Québec Diabetes Association (Plan d'alimentation avec le système d'échanges, 1993) was explained to each subject by a nutritionist. In this system, foods are categorized into the seven following groups: milk and dairy products; meat and substitutes; vegetables (one portion containing ~7 g of carbohydrates); other vegetables (one portion containing ~3-4 g of carbohydrates); fruit; bread and cereals; and fat (including oils, margarine, shortening, butter, nuts and seeds). Subjects gave their written consent to participate in this study, which received approval of the Laval University Medical Ethics Committee.

It is important to note that following the suspension of fenfluramine and dexfenfluramine because of a potential association with disturbances in cardiac valvular function (Khan et al, 1998; Weissman et al, 1998), all subjects (including placebos) were subjected to an echocardiogram. Following this assessment, a detailed evaluation of cardiac valvular function was performed by cardiologists who detected no abnormalities in response to the use of fenfluramine under these conditions (Prud'homme et al, 1999).

Anthropometric measurements

Body weight was taken with a standard beam scale. Body density was determined by hydrodensitometry (Behnke & Wilmore, 1974). The closed circuit helium dilution method (Meneely & Kaltreider, 1949) was used to assess the residual lung volume. The Siri formula (1956) was used to estimate the percentage of body fat from body density. FM was calculated from the derived percentage of body fat and total body weight. Fat-free mass (FFM) was then simply calculated as a subtraction of FM from total body weight. Waist circumference was measured at mid-distance between the iliac crest and the last rib margin.

Computed tomography measurements

Computed tomography (CT) was performed on a Siemens Somaton DRH scanner (Siemens, Erlangen, Germany) according to the methodology described by Sjöström et al, (1986). Briefly, the subjects were examined in the supine position with both arms stretched above their head. CT scans were performed at both the abdominal (between L4 and L5 vertebrae) and femoral (midthigh) levels, using an abdominal scout radiograph to establish the position of scans to the nearest millimeter (Ferland et al, 1989). Total adipose tissue areas were calculated by delineating these areas with a graph pen and then computing the total adipose tissue surfaces with an attenuation range of -190 to -30 Hounsfield units (Sjöström et al, 1986) as previously described (Ferland et al, 1989). More specifically, VAT was quantified by delineating with a graph pen the intra-abdominal cavity at the internal aspect of the abdominal and oblic muscle wall surrounding the cavity and posterior aspect of the vertebral body. SAT area was assessed by subtracting the VAT area from the total adipose tissue area. TAT level was measured for both the right and the left leg (150 mm above the knee joint). For practical purposes, the mean of the two legs was calculated and this value was used in all subsequent analyses.

Statistical analysis

Jump Software 3.2.6. from the SAS Institute Inc. (Cary, NC, USA) was used for all analyses. A one-way ANOVA (sex) was applied to determine whether gender differences in pre-treatment levels of all dependent variables could be observed while a two-way ANOVA (sex and treatment) was used to compare post-treatment levels between men and women. A two-way (sex and treatment) ANOVA for repeated measures was performed to determine the effects of this weight loss program on all dependent variables. To assess site differences in fat reduction in response to weight loss in both absolute and relative ((post-treatment - pre-treatment)/pre-treatment´100) values, a three-way ANOVA (sex by site by treatment) was performed. When this ANOVA revealed a significant site by sex interaction, a Tukey-Kramer post-hoc multiple comparison test was performed to assess within-gender differences in fat reduction. To compare VAT, SAT and TAT reductions (in absolute and relative values) between genders, an ANCOVA was performed with sex, treatment and changes in FM (as a potential covariate) as independent variables. It is also important to note that the distribution of VAT, SAT and TAT was tested and that they presented a skewness <0.5. Hence, the distribution of these variables was considered normal. ANCOVA analyses were also performed with sex and treatment as independent variables as well as changes in FM and initial VAT, SAT or TAT levels as potential covariates of the changes in these variables which occurred during weight loss. Stepwise multiple regression analyses were also performed to examine predictors of changes in VAT, SAT and TAT. For these analyses, all subjects who completed the protocol (19 men and 23 premenopausal women, including subjects who lost less than 5% of their initial body weight) were included in the model to increase the variance and the chances of better determining predictors of changes in the different fat compartment during weight loss. It is important to note that, since no effect of treatment was observed for all dependent variables, scores presented throughout the manuscript are the mean values of both placebo and drug-treated individuals combined together. All data are expressed as mean±s.e.m.

Results

Table 1 presents the characteristics of subjects before and after weight loss. Age was not significantly different between men and women. Pre-treatment body weight, FFM and VAT levels were higher in men while pre-treatment FM, SAT and TAT levels were higher in women. FFM and SAT were reduced in a similar fashion in response to the treatment in both men and women. Reductions in BMI and waist circumference were also similar in men and women. Sex-by-time interactions were observed which revealed that men lost significantly more body weight, FM and VAT than did women, while women lost significantly more TAT. As for pre-treatment levels, post-treatment body weight and FM were higher in men while FM, SAT and TAT levels were still higher in women. However, VAT levels were no longer different between genders. It is noteworthy that no effect of treatment (fenfluramine vs placebo) or treatment-by-time interactions were revealed by these analyses. This should however be interpreted with caution since subjects were selected to present at least a 5% body weight loss by the end of the program. For this reason, further analyses were performed on all subjects (n=32 drug-treated and n=10 placebos) who completed this study to clarify whether fenfluramine exerts a specific effect on VAT reduction during weight loss. In order to do so, the VAT selectivity index (SI) previously described (Smith & Zachwieja, 1999) was used. Results from this procedure showed that the VAT SI was essentially the same for drug- and placebo-treated individuals (1.27 vs 1.22, respectively; NS).

Table 2 presents results pertaining to fat reduction of VAT, SAT and TAT in response to weight loss in men and women. These analyses revealed significant sex-by-site interactions for both absolute and relative changes. Further analyses revealed that absolute changes of SAT and VAT were higher than TAT changes in men. A significantly greater relative (%) decrease in the VAT compartment when compared to SAT and TAT changes was also observed in men. In women, absolute changes in SAT area were significantly greater than those in VAT and TAT. On the other hand, no difference could be observed when these comparisons were performed for relative changes of VAT, SAT and TAT areas in women. No effect of treatment (fenfluramine vs placebo) was observed as a result of these analyses.

Since positive correlations between changes in total FM and changes in VAT (r=0.47, P <0.01), SAT (r=0.56, P<0.01) and TAT (r=0.22, NS) were noted, changes in FM were considered as a covariate in this model. Hence, gender differences in VAT, SAT and TAT reductions were compared by ANCOVA while considering changes in FM as a potential covariate (Figure 1). No significant gender difference could be observed in the changes of the SAT compartment in absolute or relative values. A significantly greater reduction of VAT in absolute and relative values was observed in men in response to this intervention. Finally, a greater reduction of TAT in absolute values was also observed in women whereas relative changes were similar between genders. Once more, no effect of treatment (fenfluramine vs placebo) was observed as a result of these analyses.

Pre-treatment levels of VAT, SAT and TAT levels were significantly different between men and women. Morever, initial levels of AT from VAT (r=-0.68, P<0.001), SAT (r=-0.43, P=0.01) and TAT (r=-0.60, P<0.001) were associated with the reductions in the area of their respective fat compartment during weight loss. It was thus decided that initial levels of each of the three different fat compartments should also be added as potential covariates of changes in adipose tissue during weight loss. An ANCOVA was thus performed to determine whether gender differences in the reduction of AT from the three different sites would persist after having considered both changes in FM and initial levels of these variables as potential covariates. Figure 2 presents the results of this analysis on adjusted absolute scores (cm²) of VAT, SAT and TAT reduction. As shown in this figure, gender differences in VAT and TAT reduction were no longer observed after initial levels of VAT and TAT had also been taken into account. These analyses were not performed on relative changes since these values already take initial levels into account.

Table 3 presents stepwise multiple regression analysis on predictors of changes in VAT, SAT and TAT in men and women. The change in waist circumference was the only significant predictor of changes in VAT in men explaining 32% of the variance (P=0.01). No predictor was found for changes in SAT and TAT. In women, change in body weight was the most consistent predictor of changes in VAT, SAT and TAT since it accounted for 45 (P<0.001), 73 (P<0.001) and 71% (P<0.001) of the changes in these variables, respectively. Moreover, adding initial VAT levels also increased the predictability of changes in VAT (60%, P=0.01) just as adding initial levels of TAT increase the predictability of the changes in TAT (79%, P=0.01) in women.

Discussion

Results reported in this study show that, after a comparable body weight loss, that is -11.3 and -10.7% of initial body weight in men and women, respectively: (1) men lost more fat from the VAT compartment than from the SAT or the TAT regions, which was not the case in women; (2) gender differences in VAT reduction were independent of changes in FM; (3) gender differences in fat reduction from the VAT compartment were no longer apparent when initial levels of VAT were also considered as a potential covariate; (4) the best clinical predictor of changes in VAT in men seemed to be changes in waist circumference while in women the best clinical predictor of changes in VAT was the change in body weight.

The fact that men in the present study lost more fat from the VAT compartment than from the SAT depot is in accordance with other clinical trials which also used drug therapy to induce weight loss (Marks et al, 1996,1998). In the study of Marks et al, (1998) placebo-treated men lost significantly less VAT than men who received the dexfenfluramine treatment. We did not observe such a difference in the present study since there was no difference between placebo- and drug-treated individuals on either the amount of weight lost or on VAT reduction during this program. This discrepancy might simply be due to the fact that the placebo treated men in the Marks et al, (1998) study also lost significantly less body fat during their intervention. Nonetheless, we decided to further investigate this issue by calculating the VAT SI recently described by Smith and Zachwieja (1999) in which the relative VAT loss is divided by the relative total fat loss. In doing so, all subjects who completed the program, thus including subjects who lost less than 5% of their initial body weight, were analyzed. Results from this analysis revealed that the VAT SI was strictly the same between subjects who received the placebo and those who were treated with fenfluramine. Based on the present results, we are thus inclined to believe that fenfluramine does not affect the partitioning of fat loss when subjects who receive the active agent and the placebo lose similar amounts of their initial body weight. However, we have to reiterate that this study design might not have been appropriate to test this hypothesis because of the uneven number of subjects receiving the placebo and the active agent, so results have to be interpreted with caution. Furthermore, it is also possible that, under conditions of a longer intervention, differences in VAT reduction might have been observed between groups.

It was recently reported that in both men and women VAT was preferentially reduced when compared to other adipose tissue stores (Janssen & Ross, 1999). Our results in men support these findings since, as demonstrated in Table 2, there seems to be a gradient in the potential to lose fat (relative values) during weight loss from TAT<SAT<VAT. This is in accordance with the observation that the ₂-(antilipolytic)/-(lipolytic)-adrenoceptor ratio is the lowest in VAT, followed by the SAT and finally by the TAT region, which displays the highest ratio (Mauriège et al, 1987). In contrast, women in the present study were not characterized by a greater reduction of VAT in response to weight loss. This is surprising since women in the present study were characterized by slightly higher initial levels of VAT and also lost a comparable amount of body weight than female subjects described in the Janssen and Ross study (1999). However, this discordance might be partly explained by the fact that women in this study lost approximately 16% of their initial body fat while a mean loss of approximately 22% was reported in this previous report.

It might be of some concern that changes in a single slice measurement of VAT at the L4/L5 level might not truly represent actual changes in total VAT volume. In this sense, recent results from our group have shown that changes in L4/L5 VAT area are highly correlated with changes in partial VAT volume calculated from two slices, ie L2/L3 and L4/L5 (Paré et al, 2001). In addition, results from the present study also show changes in L4/L5 VAT area to be highly correlated (r=0.93, P<0.001) with changes in partial VAT volume calculated from two slices. We are thus inclined to think that changes in L4/L5 VAT area are representative of changes in total VAT volume during weight loss. Another important aspect which can raise some concern is whether or not the reduction of the area on the image generated by the CT technique truly represents a reduction in adipose tissue per se. In this regard, it has been demonstrated that adipose tissue is mainly composed of mature adipocytes (~66%), the remaining cells being blood cells, endothelial cells, pericytes and adipose precursor cells (Ailhaud et al, 1992). Of note, mature adipocytes are mainly filled (~95%) by lipid which makes their content poor in water. The lipid droplets within the adipocyte differ in size and this is reflected by various fat cell diameters that could be measured with a microscope following an adipose tissue explant digest with collagenase. With this technique, we have recently reported a significant decrease in subcutaneous fat cell size in response to weight loss in men and women of the current study (Mauriège et al, 1999). This observation provides support for a specific decreased adipocyte lipid content in response to weight loss. Although the size of visceral adipocytes was not measured in the present study, we can assume that a similar significant decrease in lipid content also occurred in visceral fat cells since subcutaneous and visceral adipocyte sizes are strongly related together (Hoffstedt et al, 1997). On the basis of these observations, we believe that changes in VAT area reported in the current study are representative of a loss of fat from the adipocyte in this compartment.

The most striking difference of fat loss between genders was noted for the visceral depot where men displayed about twice as much reduction as did women even after differences in FM changes had been taken into account. This observation is in accordance with two other recent studies that reported differences of the same magnitude (Goodpaster et al, 1999; Wirth & Steinmetz, 1998). However, it has been suggested that individuals who display large initial amounts of VAT are also characterized by a more substantial reduction of this depot during weight loss interventions (Fujioka et al, 1991; Leenen et al, 1992; Marks et al, 1996,1998). Since men in the present study displayed VAT levels that were higher than those measured in women, initial levels of VAT were also considered as a potential covariate of the changes of VAT which occurred in response to weight loss. Accordingly, taking initial VAT levels into account along with changes in FM considerably reduced the gender difference which was initially observed during this weight loss program (Figure 2), which is in accordance with another recent study (Janssen & Ross, 1999). Nonetheless, adjusted scores of changes in VAT still remained quite different between men and women since a ~30% difference could still be observed. In this context, we cannot rule out that gender differences in the intrinsic properties of VAT metabolism, as is the case for the density of ₂-(antilipolytic) and ₃-(lipolytic) adrenoceptors (Lönnqvist et al, 1997) might be partly responsible for this difference of VAT reduction between men and women which is generally observed during weight loss.

Total FM, SAT and TAT were significantly greater in women both before and after weight loss. In contrast, although men started out with much more VAT tissue than did women, post-treatment levels were the same between genders. Although gender differences in VAT reduction are largely explained by pre-treatment differences in the size of this fat depot, one important clinical observation still remains, and that is the fact that, in response to a comparable weight loss (-11% of initial body weight), women lose less VAT than do men. Since improvements of the metabolic risk profile are closely associated to reductions in VAT (Fujioka et al, 1991; Marks et al, 1998; Wirth & Steinmetz, 1998), it is possible that the more pronounced improvements of the metabolic risk profile which are observed in men in response to weight loss (Leenen et al, 1993) are tributary to a greater reduction in VAT levels. Moreover, the fact that changes in VAT are also at least partly independent from changes in total FM is also clinically relevant since it implies that we cannot assume with certainty that a large fat loss will systematically lead to a large reduction in VAT. Once more, this might also explain why more marked improvements of the metabolic profile are observed in some individuals than in others after a comparable fat loss.

Since VAT is more closely associated to health complications than SAT (Björntorp, 1991; Després, 1991; Kissebah, 1991), it would be useful to be able to predict which individuals will show the most pronounced reduction in this fat compartment in response to weight loss. Although numerous reports suggest that the initial level of VAT is a good predictor of VAT reduction during weight loss (Fujioka et al, 1991; Leenen et al, 1992), VAT measurement is not an easily accessible tool in day-to-day practice. In this sense, results from the present study, as did others (Ross et al, 1996a), demonstrate that the change in waist circumference is the best predictor of changes in VAT in men. In women, the most consistent predictor of changes in VAT seems to be changes in body weight. This latter observation is in agreement with another recent study that demonstrated that body weight change was the only significant correlate of changes in VAT in a small sample of morbid obese women after laparascopic surgery (Busetto et al, 2000). These results should however be interpreted with caution since some studies have also shown that significant changes in VAT can occur with very small changes in body weight when exercise is part of the intervention (Mourier et al, 1997; Schwartz et al, 1991; Thomas et al, 2000; Thong et al, 2000; Treuth et al, 1995). Since exercise has been shown to be related to an increase in sympathetic nervous system activity (Poehlman & Danforth, 1991; Tremblay et al, 1992), and that VAT has a greater lipolytic potential than SAT or TAT (Mauriège et al, 1987), it is possible that VAT may be reduced to a greater extent when exercise is part of the intervention. On the other hand, energy deprivation without exercise has been shown to reduce sympathetic nervous system activity (Arone et al, 1995), which could possibly lead to a decreased contribution of VAT to energy production when compared to an intervention which includes exercise. Thus the finding that changes in body weight are a significant predictor of changes in VAT might not be applicable to interventions which include exercise as part of the treatment. Our results lend support to these observations, since no significant reduction in VAT was observed in subjects that were excluded from the present study because they had lost less than 5% of their initial body weight. Once more, this should be interpreted with some reservations since recent results tend to show that, after a comparable weight loss as that observed in the present study, no significant difference in VAT loss could be observed between groups subjected to either a caloric restriction, a caloric restriction+aerobic exercise, or a caloric restriction + resistance training (Janssen & Ross, 1999). Furthermore, even if changes in waist circumference and body weight are very accessible clinical tools, since they only predict about one-third to half of the variance of VAT changes, their use as a valid reflection of the changes in VAT which occur during weight loss in a clinical context is limited.

In summary, men lost significantly more VAT than SAT or TAT, which was not the case for women. Moreover, men seemed to lose more fat from the VAT compartment than did women independently of changes in FM. However, gender differences in the reduction of fat from the VAT compartment appeared to be mainly explained by differences in initial levels of VAT.

Acknowledgements

This research was supported by grants from Servier Canada.

Ailhaud G, Grimaldi P, Négrel R. (1992). Cellular and molecular aspects of adipose tissue development. A. Rev. Nutr., 12: 207-333.

Arone LJ, Mackintosh R, Rosenbaum M, Leibel RL, Hirsch J. (1995). Autonomic nervous system activity in weight gain and weight loss. Am. J. Physiol., 269: R222-R225. MEDLINE

Behnke AR, Wilmore JH. (1974). Evaluation and Regulation of Body Build and Composition. 20-37, Englewood Cliffs, NJ: Prentice-Hall.

Björntorp P. (1991). Metabolic implications of body fat distribution. Diabetes Care, 14: 1132-1143. MEDLINE

Busetto L, Tregnaghi A, Bussolotto M, Sergi G, Beninca P, Ceccon A, Giantin V, Fiore D, Enzi G. (2000). Visceral fat loss evaluated by total body magnetic resonance imaging in obese women operated with laparascopic adjustable silicone gastric banding. Int. J. Obes. Relat. Metab. Disord., 24: 60-69. MEDLINE

Canadian Nutrient File, (1991). Health and Welfare Canada.

Després J-P. (1991). Obesity and lipid metabolism: relevance of body fat distribution. Curr. Opin. Lipidol., 2: 5-15.

Ferland M, Després JP, Tremblay A, Pinault S, Nadeau A, Moorjani S, Lupien PJ, Thériault, Bouchard C. (1989). Assessment of adipose tissue distribution by computed axial tomography in obese women: association with body density and anthropometric measurements. Br. J. Nutr., 61: 139-148. MEDLINE

Fujioka S, Matsuzawa Y, Tokunaga K, Kawamoto T, Kobatake T, Keno Y, Kotani K, Yoshida S, Tarui S. (1991). Improvement of glucose and lipid metabolism associated with selective reduction of intra-abdominal visceral fat in premenopausal women with visceral fat obesity. Int. J. Obes., 15: 853-859. MEDLINE

Goodpaster BH, Kelley DE, Wing RR, Meier A, Thaete FL. (1999). Effects of weight loss on regional fat distribution and insulin sensitivity in obesity. Diabetes, 48: 839-847. MEDLINE

Gray DS, Fujioka K, Colletti PM, Kim H, Devine W, Cuyegkeng T, Pappas T. (1991). Magnetic-resonance imaging used for determining fat distribution in obesity and diabetes. Am. J. Clin. Nutr., 54: 623-627. MEDLINE

Hellmer J, Marcus C, Sonnenfeld T, Arner P. (1992). Mechanisms for differences in lipolysis between human subcutaneous and omental fat cells. J. Clin. Endocrinol. Metab., 75: 15-20. MEDLINE

Hoffstedt J, Arner P, Hellers G, Lonnqvist F. (1997). Variation in adrenergic regulation of lipolysis between omental and subcutaneous adipocytes from obese and non-obese men. J. Lipid Res., 38: 795-804. MEDLINE

Janssen I, Ross R. (1999). Effects of sex on the change in visceral, subcutaneous adipose tissue and skeletal muscle in response to weight loss. Int. J. Obes. Relat. Metab. Disord., 23: 1035-1046. MEDLINE

Khan MA, Herzog CA, St Peter JV, Hartley GG, Madlon-Kay R, Dick CD, Asinger RW, Vessey JT. (1998). The prevalence of cardiac valvular insufficiency assessed by transthoracic echocardiography in obese patients treated with appetite-suppressant drugs. New Engl. J. Med., 10: 713-718.

Kissebah AH. (1991). Insulin resistance in visceral obesity. Int. J. Obes., 15: (Suppl 2) 109-115. MEDLINE

Leenen R, van der Kooy K, Durenberg P, Seidell JC, Weststrate JA, Schouten FJM, Hautvast JGAJ. (1992). Visceral fat accumulation in obese subjects: relation to energy expenditure and response to weight loss. Am. J. Physiol., 263: E913-E919. MEDLINE

Leenen R, van der Kooy K, Droop A, Seidell JC, Deurenberg P, Weststrate JA, Hautvast JG. (1993). Visceral fat loss measured by magnetic resonance imaging in relation to changes in serum lipid levels of obese men and women. Arterioscler. Thromb., 13: 487-494. MEDLINE

Leibel RL, Hirsch J. (1987). Site- and sex-related differences in adrenoceptor status of human adipose tissue. J. Clin. Endocrinol. Metab., 64: 1205-1210. MEDLINE

Lönnqvist F, Thorne A, Large V, Arner P. (1997). Sex differences in visceral fat lipolysis and metabolic complications of obesity. Arterioscles. Thromb. Vasc. Biol., 17: 1472-1480.

Marks SJ, Moore NR, Clark ML, Strauss BJ, Hockaday TD. (1996). Reduction of visceral adipose tissue and improvement of metabolic indices: effect of dexfenfluramine in NIDDM. Obes. Res., 4: 1-7. MEDLINE

Marks SJ, Chin S, Strauss BJ. (1998). The metabolic effects of preferential reduction of visceral adipose tissue in abdominally obese men. Int. J. Obes. Relat. Metab. Disord., 22: 893-898. MEDLINE

Mauriège P, Galitzky J, Berlan M, Lafontan M. (1987). Heterogeneous distribution of beta- and alpha₂-adrenoceptor binding sites in human fat cells from various deposits: functional consequences. Eur. J. Clin. Invest., 17: 156-165. MEDLINE

Mauriège P, Prud'Homme D, Lemieux S, Tremblay A, Després J-P. (1995). Regional differences in adipose tissue lipolysis from lean and obese women: existence of postreceptor alterations. Am. J. Physiol., 269: E341-E350. MEDLINE

Mauriège P, Imbeault P, Langin D, Lacaille M, Alméras N, Tremblay A, Després J-P. (1999). Regional and gender variations in adipose tissue lipolysis in response to weight loss. J. Lipid Res., 40: 1559-1571. MEDLINE

Meneely EA, Kaltreider NL. (1949). Volume of the lung determined by helium dilution. J. Clin. Invest., 28: 129-139.

Mourier A, Gautier JF, De Kerviler E, Bigard AX, Villette JM, Garnier JP, Duvallet A, Guezennec CY, Cathelineau G. (1997). Mobilization of visceral adipose tissue related to the improvement in insulin sensitivity in response to physical training in NIDDM. Effects of branched-chain amino acid supplements. Diabetes Care, 20: 385-391. MEDLINE

Paré A, Dumont M, Lemieux I, Brochu M, Alméras N, Lemieux S, Prud'homme D, Després J-P. (2001). Is the relationship between visceral adipose tissue and waist girth altered by weight loss in abdominally obese men? Obes. Res., 9: 526-534. MEDLINE

Plan d'alimentation avec le système d'échanges, (1993). Montréal: Association Diabète Québec, Groupe Litho Graphique.

Poehlman ET, Danforth E. (1991). Endurance training increases metabolic rate and norepinephrine appearance rate in older individuals. Am. J. Physiol., 261: E233-E239. MEDLINE

Prud'homme D, Langlais M, Samson MP, Gallagher P, Turcotte J, Tremblay A, Després J-P. (1999). Lack of major cardiac valvular abnormalities in asymptomathic obese men and women following a 3-month fenfluramine or dexfenfluramine treatment. Int. J. Obes. Relat. Metab. Disord., 23: S175.

Ross R, Rissanen J, Hudson R. (1996a). Sensitivity associated with the identification of visceral adipose tissue levels using waist circumference in men and women: effects of weight loss. Int. J. Obes. Relat. Metab. Disord., 20: 533-538. MEDLINE

Ross R, Rissanen J, Pedwell H, Clifford J, Shragge P. (1996b). Influence of diet and exercise on skeletal muscle and visceral adipose tissue in men. J. Appl. Physiol., 81: 2445-2455. MEDLINE

Schwartz RS, Shuman WP, Larson V, Cain KC, Fellingham GW, Beard JC, Kahn SE, Stratton JR, Cerqueira MD, Abrass IB. (1991). The effect of intensive endurance exercise training on body fat distribution in young and older men. Metabolism, 40: 545-551. MEDLINE

Siri WE. (1956). The gross composition of the body. Adv. Biol. Med. Physiol., 4: 239-280.

Sjöström L, Kvist H, Cederblad A, Tylen U. (1986). Determination of total adipose tissue and body fat in women by computed tomography, ⁴⁰K, and tritium. Am. J. Physiol., 250: E736-745. MEDLINE

Smith SR, Zachwieja JJ. (1999). Visceral adipose tissue: a critical review of intervention strategies. Int. J. Obes. Relat. Metab. Disord., 23: 329-335. MEDLINE

Stallone DD, Stunkard AJ, Wadden TA, Foster GD, Boorstein J, Arger P. (1991). Weight loss and fat distribution: a feasibility study using computed tomography. Int. J. Obes., 15: 775-780. MEDLINE

Thomas EL, Brynes AE, McCarthy J, Goldstone AP, Hajnal JV, Saeed N, Frost G, Bell JD. (2000). Preferential loss of visceral fat following aerobic exercise, measured by magnetic resonance imaging. Lipids, 35: 769-776. MEDLINE

Thong FS, Hudson R, Ross R, Janssen I, Graham TE. (2000). Plasma leptin in moderately obese men: independent effects of weight loss and aerobic exercise. Am. J. Physiol., 279: E307-E313.

Tremblay A, Coveney JP, Després JP, Nadeau A, Prud'homme D. (1992). Increased resting metabolic rate and lipid oxidation in exercise-trained individuals: evidence for a role of beta adrenergic stimulation. Can. J. Physiol. Phamac., 70: 1342-1347.

Treuth MS, Hunter GR, Kekes-Szabo T, Weinsier RL, Goran MI, Berland L. (1995). Reduction in intra-abdominal tissue after strength training in older women. Am. J. Physiol., 78: 1425-1431.

Weissman NJ, Tighe JFJ, Gottdiener JS, Gwynne JT. (1998). An assessment of heart-valve abnormalities in obese patients taking dexfenfluramine, sustained-release dexfenfluramine, or placebo. Sustained-Release Dexfenfluramine Study Group. New Engl. J. Med., 10: 725-732.

Wirth A, Steinmetz B. (1998). Gender differences in changes in subcutaneous and intra-abdominal fat during weight reduction: an ultrasound study. Obes. Res., 6: 393-399. MEDLINE

Zamboni M, Armellini F, Turcato E, Todesco T, Bissoli L, Bergamo-Andreis IA, Bosello O. (1993). Effect of weight loss on regional body fat distribution in premenopausal women. Am. J. Clin. Nutr., 58: 29-34. MEDLINE

Figure 1 Changes (in absolute and relative values) in visceral adipose (VAT), subcutaneous abdominal adipose tissue (SAT) and thigh adipose tissue (TAT) in response to weight loss in men (n=17) and women (n=17). Means are adjusted scores for changes in FM by analysis of covariance. *, **, *** P<0.05, 0.01 and 0.001, respectively.

Figure 2 Changes (in absolute values) in visceral adipose (VAT), subcutaneous abdominal adipose tissue (SAT) and thigh adipose tissue (TAT) in response to weight loss in men (n=17) and women (n=17). Means are adjusted scores for changes in FM and pre-weight loss VAT, SAT or TAT levels by analysis of covariance.

Table 1 Subjects' characteristics before and after weight loss

Table 2 Reduction of fat in absolute and relative values from VAT, SAT and TAT

Table 3 Stepwise multiple regression analysis examining predictors of changes in VAT, SAT and TAT during weight loss in men and women