Influence of sex on total and regional fat loss in overweight and obese men and women

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1 (2009) 33, & 2009 Macmillan Publishers Limited All rights reserved /09 $ ORIGINAL ARTICLE Influence of sex on total and regional fat loss in overweight and obese men and women JL Kuk 1 and R Ross 2 1 School of Kinesiology and Health Science, Faculty of Health Science, York University, Toronto, Ontario, Canada and 2 School of Kinesiology and Health Studies, Department of Medicine, Division of Endocrinology and Metabolism, Queen s University, Kingston, Ontario, Canada Objective: To determine the influence of sex on the association between reductions in body weight (BW) and waist circumference (WC) with reductions in total (TAT), subcutaneous (SAT) and visceral adipose tissue (VAT) in response to lifestylebased interventions. Design: Changes in TAT, SAT and VAT were assessed using magnetic resonance imaging in 81 men and 72 women who had participated in various diet and/or exercise interventions at Queen s University, Ontario, Canada. Results: Reductions in BW and WC were significantly (Po0.001) correlated with TAT, SAT and VAT loss in men and women. For a given weight loss, men had a significantly greater decrease in WC than women, and the sex difference in WC reduction increased with increasing weight loss (Po0.05). Similarly, for a given reduction in BW or WC, men have significantly greater reductions in VAT, but smaller reductions in total and lower body SAT than women, differences that progressively increased in magnitude with the increasing BW or WC loss (Po0.05). Accordingly, there were no sex differences in the TAT reduction for a given BW or WC reduction (P40.05). Reductions in BW and WC were both independent predictors of VAT loss. Conclusions: These observations suggest that for a given reduction in BW or WC, men lose more VAT and less SAT than women; however, the TAT loss observed for a given reduction in BW or WC in men and women is not different. (2009) 33, ; doi: /ijo ; published online 10 March 2009 Keywords: weight loss; body composition; gender; waist; visceral fat Introduction It is well known that adiposity is reduced in response to weight loss in both men and women. 1 6 Whether sex influences the mobilization and pattern of total and regional adipose tissue (AT) with weight loss is unclear. Several studies reporting that men lose more visceral AT (VAT) than women are confounded by greater weight losses in men. 3,7,8 Nevertheless, studies that report a similar weight loss 1,2,9 still observe a greater reduction in VAT in men than in women. However, as reductions in AT are related to their initial values, 2,3 men may be expected to lose more VAT because they generally have more VAT than women. Correspondence: Dr R Ross, School of Kinesiology and Health Studies, Department of Medicine, Division of Endocrinology and Metabolism, Queen s University, Kingston, Ontario, Canada. rossr@queensu.ca Received 26 November 2008; revised 4 February 2009; accepted 8 February 2009; published online 10 March 2009 Indeed, preliminary studies suggest that after controlling for weight loss and baseline sex differences in VAT, sex differences in the reduction in VAT are reduced to borderline nonsignificance (P ¼ 0.07), 2 if not abolished all together. 3,6 Earlier studies with limited sample sizes have reported nonsignificant sex differences of 10 30% that may be of clinical relevance. 2,3,6 Earlier null observations may be due to smaller sample sizes and lack of statistical power to observe relevant sex differences. Of note, the lone study that reported borderline significant sex differences was the only study that had a sample size 430 per sex. Thus, the primary objective of this study was to determine whether sex was associated with differences in AT mobilization for a given reduction in body weight (BW) and/or waist circumference (WC). A secondary objective was to examine sex differences in AT mobilization using other commonly used anthropometric indices (that is, body mass index, waistto-hip ratio (WHR) and hip circumference). These markers are commonly used in weight reduction studies to characterize changes in fat distribution, and the influence of sex on these relationships has to be described yet.

2 630 Materials and methods Subjects Subjects consisted of 81 men and 72 women (body mass index, BMI 427) who had participated in various diet and/or exercise intervention studies wherein body composition was assessed using whole-body magnetic resonance imaging (MRI). 4 6,10 12 Briefly, the study interventions consisted of weeks of caloric restriction (n ¼ 45), exercise (n ¼ 67) or a combination of caloric restriction and exercise (n ¼ 41). Of these, 60 of the 153 were earlier reported in a study examining the effect of sex on body composition, but was likely underpowered for these analyses. 6 We certify that all applicable institutional regulations concerning the ethical use of human volunteers were followed during this research. All subjects gave informed and written consent to participate in the studies, which were conducted in accordance with the ethical guidelines of Queen s University. Anthropometric measurements Body mass was measured to the nearest 0.1 kg on a calibrated balance. Standing height was measured to the nearest 0.1 cm using a wall-mounted stadiometer. WC was taken at the level of the last rib to the nearest 0.1 cm after a normal expiration. Hip circumference was taken at the maximal gluteal protuberance. Measurement of total and regional fat by magnetic resonance imaging Whole-body MRI data (41 47 equidistant images) were obtained with a General Electric, 1.5. Tesla magnet using an established protocol described in detail earlier. 12 Once acquired, the MRI data were transferred to a stand-alone workstation for analysis using specially designed computer software (Tomovision Inc., Montreal, Canada), the procedures for which have been described earlier. 12,13 Total AT (TAT) mass was determined using images. Abdominal SAT (ASAT) and VAT was calculated using the five images extending from 5 cm below to 15 cm above L4 L5. Upper body AT consisted of the all images superior to the abdomen, and did not include the abdominal region. Lower body AT was derived using all images distal to the abdomen. AT volumes (L) were converted to mass units (kg) by multiplying the volumes by the assumed constant density (0.92 kg l 1 ). 14 Statistical analyses Group data are presented as means±s.d. Sex differences at baseline and change scores were assessed using independent t-tests and ANCOVA, adjusted for baseline differences. Pearson s correlations and multiple linear regression analyses were performed to determine the relationship between changes in the anthropometric- (WC, BW and BMI) and MRI-measured AT loss (TAT, SAT and VAT). Age, the intervention type and the baseline value for the dependent variable were entered as covariates. Models were tested for main effects of sex and its interactions in all the multiple linear regression analyses. Residual analyses were performed to determine significant points of influence in the final models. Significant outliers with large jackknife residuals or large Cook s D with high leverage were excluded from the analyses. Five individuals were eliminated from all analyses, as they were identified as influential points in more than half the analyses, and up to an additional three individuals were eliminated on a case-by-case basis resulting in a sample size of Exclusion of the outliers did not alter the significance of the results, but did tend to reduce the magnitude of the sex differences. To allow for comparisons between men and women, figures were standardized using sex-specific mean values. All statistical procedures were performed using SAS v8. Results The baseline and changes in subject characteristics are listed in Table 1. In response to exercise and/or caloric restriction, the men and women had a large range in weight change ( þ 1.3 to 19.1%). Despite significant baseline sex differences in all measures, except BMI, there were no sex differences in the anthropometric or AT changes in response to the interventions after control for baseline sex differences. The associations between reductions in body weight (DBW), reductions in BMI (DBMI) and reductions in WC (DWC), WHR and hip circumference with reductions in total AT (DTAT), SAT (DSAT), ASAT (DASAT) and VAT (DVAT) are shown in Table 2. Reductions in WC, BW, BMI and hip circumference were significantly associated with reductions in all the AT variables (except VAT and hip circumference in women). Changes in WHR were not significantly associated with changes in any of the AT variables in women, and WHR was generally a weaker correlate of AT changes in men. Influence of sex on changes in abdominal AT The slope of the association between DWC and DBW (Figure 1) or DBMI was significantly higher in men than in women (Interaction, Po0.05), with no differences in the intercept (main effect, P40.10). Similarly, the slope of the association between DVAT with DBW and DWC (Figure 2 and Table 3) was significantly higher in men than in women (Interaction, Po0.05), with no differences in the intercept (main effect, P40.10). Adjustment for baseline differences in WC or VAT did not alter the significance of the results. When both DBW and DWC were entered in the model, both variables were significant independent predictors of DVAT. Before adjustment for baseline ASAT, men lost significantly less ASAT for a given weight loss, as compared with women (Table 3). This sex difference was eliminated after adjustment for baseline levels of ASAT. Conversely, there was a small, but

3 Table 1 Baseline and changes in subject characteristics 631 Men Women Baseline Reduction Baseline Reduction N Age (years) 44.3± ±6.7* BMI (kg/m 2 ) 31.9± ± ± ±1.4 Weight (kg) 99.9± ± ±11.2* 6.7±4.0 WC (cm) 108.4± ± ±8.8* 5.9±3.7 WHR a 0.98± ± ±0.06* 0.01±0.03** Hip circumference (cm) a 110.9± ± ±8.2* 5.6±4.3** Total AT (kg) 32.1± ± ±8.0* 6.1±3.2 Subcutaneous AT (kg) 24.6± ± ±7.3* 5.3±3.1** Upper body SAT (kg) 4.7± ± ±1.6* 1.0±0.7** Lower body SAT 8.6± ± ±3.1* 2.1±1.7** Abdominal SAT (kg) 11.3± ± ±4.0* 2.3±1.7 Visceral AT (kg) 3.5± ± ±0.8* 0.5±0.4** Abbreviations: AT, adipose tissue; BMI, body mass index; SAT, subcutaneous adipose tissue; WC, waist circumference; WHR, waist-to-hip ratio. a Men: n ¼ 76, Women: n ¼ 67. *Significant sex difference at baseline (Po0.05). **Significant sex difference in the reduction before adjusting for baseline differences. No significant sex difference in the reduction with the intervention after adjusting for baseline differences (P40.10). Table 2 Simple associations between reductions in anthropometric measures with reductions in total, subcutaneous and visceral AT Reduction in Total AT Subcutaneous AT Abdominal SAT Visceral AT Men Women Men Women Men Women Men Women WC 0.81* 0.65* 0.79* 0.68* 0.73* 0.49* 0.58* 0.31* BMI 0.87* 0.86* 0.86* 0.88* 0.83* 0.81* 0.57* 0.38* Body Weight 0.87* 0.85* 0.88* 0.86* 0.84* 0.82* 0.56* 0.38* WHR 0.31* * * 0.01 Hip Circ. 0.65* 0.48* 0.65* 0.40* 0.62* 0.44* 0.32* 0.23 Abbreviations: AT, adipose tissue; SAT, subcutaneous adipose tissue. *Significant association at Po0.05. significant, main effect of sex on the relationship between DASAT and DWC, after control for baseline levels of ASAT, wherein men lost more ASAT than women for a given DWC (Po0.05). When both BW and WC were entered in the model, DBW (Po0.05) and not DWC (P40.10) was a significant independent predictor of DASAT. Influence of sex on changes in total and regional SAT The slope of the association between DSAT with DBW and DWC was significantly lower in men than in women (Interaction, Po0.05), but with no differences in the intercept (main effect, P40.10). In particular, for a given DBW or DWC, men tend to lose less SAT in the lower body (Po0.05) compared with women, but with no sex differences observed in SAT reductions in the upper body (P40.10). As men have significantly greater VAT loss, and smaller SAT loss for a given DBW or DWC compared with women, there was no significant effect of sex on the relationship between DTAT and DBW or DWC (P40.10). Reduction in Waist Circumference (cm) Influence of sex on changes in regional AT for a given TAT loss The relationship between total and regional AT loss is shown in Figure 3. For a given DTAT, men lose more VAT and ASAT, less lower body SAT, and are not different in terms of upper body SAT loss as compared with women. Discussion Main Effect: NS Interaction: P < Reduction in Body Weight (kg) Figure 1 Pattern of waist circumference (WC) reduction in response to reductions in body weight (BW) in men and women. Scatter points are the predicted WC loss values after standardized to 40 years of age, and with control for mean study group effect and mean sex-specific baseline WC. Men: filled squares, women: open squares. The primary finding of this study is that there are sex differences in the pattern of VAT and SAT mobilization associated with reductions in BW and WC. Men have greater reductions in VAT and smaller reductions in SAT for a given weight loss or reduction in WC as compared with women. Further, reductions in both WC and BW are significant

4 632 a Reduction in Visceral AT (kg) Main Effect: NS Interaction: P < Reduction in Body Weight (kg) b Reduction in Visceral AT (kg) Main Effect: NS Interaction: P < Reduction in Waist Circumference (cm) Figure 2 Pattern of visceral adipose tissue (VAT) loss in response to reductions in body weight (BW) (a) or waist circumference (WC) (b) in men and women. Scatter points are the predicted VAT loss values after standardized to 40 years of age, and with control for mean study group effect and mean sex-specific baseline VAT. Men: filled squares, women: open squares. Table 3 Sex differences in pattern of WC or AT loss in response to reductions in body weight, WC or total AT Weight loss (3 15 kg) WC Reduction (3 15 cm) Total AT loss (3 12 kg) Non-adj* Adj w Non-adj* Adj w Non-adj* Adj w WC (cm) #4~ #4~ F F F F Total AT (kg) #o~ NS NS NS F F Subcutaneous AT (kg) #o~ #o~ #o~ #o~ #o~ #o~ Upper Body SAT (kg) #o~ NS #o~ NS NS NS Lower Body SAT (kg) #o~ #o~ #o~ #o~ #o~ #o~ Abdominal SAT (kg) #o~ NS NS #4~ NS #4~ Visceral AT (kg) #4~ #4~ #4~ #4~ #4~ #4~ Abbreviations: AT, adipose tissue; Non-adj, non-adjustive; NS, Not significant; SAT, subcutaneous adipose tissue; WC, waist circumference. Sex differences in the reduction in WC and total and regional adipose tissue (AT) with reductions in body weight, WC and total AT without* and with w adjustment for baseline differences in WC or total and regional AT. All models are adjusted for age and the type of intervention. independent predictors of VAT loss. This suggests that reductions in both WC and BW are associated with greater reductions in VAT, and thus both are important in assessing changes in body composition. This study shows that men and women differ in the type and location, but not in the TAT loss they experience for a given weight loss or reduction in WC. For a given level of obesity reduction (BW, WC or TAT) men lose more VAT and less SAT compared with women. In particular, men lose significantly less SAT from the lower body than women, but are comparable in upper body and ASAT loss. This contrasts with others that did not observe sex differences. 2,3,6 The disparate findings may be partially explained by our larger sample size (N ¼ 153 vs 30 78) or due to the use of a continuous statistical analysis: two factors that would improve statistical power to determine sex differences. Earlier studies have used an adjusted means design to examine sex difference in fat loss, which can only be used if there is no interaction effect. Our study clearly shows that the degree to which men and women differ in terms of fat loss is dependent on the magnitude of the obesity reduction (interaction effect). This implies that future interventions examining changes in the body composition may be able to collapse their samples across sex in situations of minimal weight loss, but not in studies with more severe weight loss. Factors that are responsible for the sex differences in regional fat loss are unclear, but may be related to the baseline differences fat distribution. It is well documented that the magnitude of the expected AT loss is related to the initial values of AT. 2,3 Indeed, the greater reductions in VAT and smaller reductions in lower body SAT may simply reflect the greater baseline levels of VAT and smaller baseline levels of lower body SAT in men compared with women. However, after statistically controlling for baseline sex differences in visceral and subcutaneous adiposity, the sex differences in the reduction in VAT and SAT remained. Alternative explanations may include sex differences in AT sympathetic activation or hormone levels, 15,16 but remains a topic for future investigations. Sex differences in the pattern of obesity reduction may also influence the degree to which weight loss is associated with the metabolic improvements in men and women. Past studies clearly show that VAT is a strong independent predictor of morbidity 17,18 and mortality. 19 Together, these results would suggest that men might experience greater improvements in health risk for a given amount of weight loss or reduction in WC. For a similar weight loss, middleaged men and women are reported to have similar improvements in their lipid profile, 20 but may have a greater improvement in glucose metabolism 21 and insulin sensitivity. 4,5 Regardless of whether sex differences exist, it is clear that decreases in visceral adiposity are associated with improvements in health risk. Several reports have showed that changes in BMI and WC are both simple correlates of reductions in ASAT and VAT depots. 2,22,23 This report extends earlier observations, showing that both BMI and WC are independent predictors of reductions in VAT in men and women. This is in line with

5 a 100% b 100% 633 Reduction in AT (kg) 80% Lower Body SAT 34% 60% Upper Body SAT 31% 40% Abdominal SAT 18% 20% Visceral AT 17% 0% Reduction in Total AT (kg) Reduction in AT (kg) 80% Lower Body SAT 41% * 60% 40% Upper Body SAT 33% 20% Abdominal SAT 17% * 0% Visceral AT 9% * Reduction in Total AT (kg) Figure 3 Contribution of visceral and regional subcutaneous AT (SAT) loss in relation to the total AT (TAT) loss in men (a) and women (b). Standardized to 40 years of age. The mean group effect and mean sex-specific baseline visceral or regional SAT values were included in the model. *Significant sex difference (Po0.05). observations from exercise interventions 4,24 that report reductions in VAT are apparent through reductions in WC, despite no change in BW. Together, these findings reinforce the importance of acquiring both measures for assessing changes in visceral adiposity. Unlike changes in WC, BMI or BW, changes in WHR were not consistently associated with corresponding changes in VAT or other AT depots, particularly, in women. WHR is often reported in cross-sectional studies to be a superior predictor of VAT 25 and metabolic risk, 26 but is clearly an inferior measure in longitudinal studies. Thus, in accordance with earlier observations, 2,27,28 we highlight an important, but not often reported, limitation of using WHR in longitudinal studies, particularly in women. The strengths and limitations of this study warrant mention. Firstly, this study included a large homogeneous sample of abdominally obese, middle-aged Caucasian men and women. This may limit the generalizability of the results of our study, but should not affect the internal validity. Secondly, these men and women underwent various diet and/or exercise interventions that induced a wide range of weight losses. It is unclear whether diet and/or exercise interventions differ in the pattern of fat loss, or whether they may have affected the sex differences that we observed in this study. However, this is unlikely to affect our study results, as similar numbers of men and women were randomized to each diet and/or exercise intervention. Finally, as we do not have metabolic change data in this study, it is unclear whether these sex differences in AT loss translate into differences in metabolic improvement between men and women. In conclusion, the findings of this study suggest that there are sex differences in the type, but not in the TAT loss observed for a given reduction in BW or WC. For a given reduction in BW or WC, men tend to lose more VAT and less SAT than women. Further, BW and WC are both independent predictors of changes in VAT. Consequently, both of these anthropometric measures may be useful in characterizing changes in adiposity and related morbidity risk. Conflict of interest The authors state no conflict of interest. Acknowledgements This research was supported in part by research grants from the Canadian Institutes of Health Research to Robert Ross (MT13448). Both authors were involved in the conception, analysis and writing of the paper. References 1 Wirth A, Steinmetz B. Gender differences in changes in subcutaneous and intra-abdominal fat during weight reduction: an ultrasound study. Obes Res 1998; 6: van der Kooy K, Leenen R, Seidell JC, Deurenberg P, Droop A, Bakker CJ. Waist-hip ratio is a poor predictor of changes in visceral fat. Am J Clin Nutr 1993; 57: Doucet E, St-Pierre S, Almeras N, Imbeault P, Mauriege P, Pascot A et al. Reduction of visceral adipose tissue during weight loss. Eur J Clin Nutr 2002; 56: Ross R, Janssen I, Dawson J, Kungl AM, Kuk JL, Wong SL et al. Exercise-induced reduction in obesity and insulin resistance in women: a randomized controlled trial. Obes Res 2004; 12: Ross R, Dagnone D, Jones PJ, Smith H, Paddags A, Hudson R et al. Reduction in obesity and related comorbid conditions after dietinduced weight loss or exercise-induced weight loss in men. A randomized, controlled trial. Ann Intern Med 2000; 133: Janssen I, Ross R. 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 1999; 23: Donnelly JE, Hill JO, Jacobsen DJ, Potteiger J, Sullivan DK, Johnson SL et al. Effects of a 16-month randomized controlled exercise trial on body weight and composition in young, overweight men and women: the midwest exercise trial. Arch Intern Med 2003; 163: Wilmore JH, Despres JP, Stanforth PR, Mandel S, Rice T, Gagnon J et al. Alterations in body weight and composition consequent to 20 wk of endurance training: the HERITAGE Family Study. Am J Clin Nutr 1999; 70:

6 634 9 Leenen R, van der Kooy K, Deurenberg P, Seidell JC, Weststrate JA, Schouten FJ et al. Visceral fat accumulation in obese subjects: relation to energy expenditure and response to weight loss. Am J Physiol Endocrinol Metab 1992; 263: E913 E Lee S, Kuk JL, Davidson LE, Hudson R, Kilpatrick K, Graham TE et al. Exercise without weight loss is an effective strategy for obesity reduction in obese individuals with and without type 2 diabetes. J Appl Physiol 2005; 99: Ross R, Pedwell H, Rissanen J. Effects of energy restriction and exercise on skeletal muscle and adipose tissue in women as measured by magnetic resonance imaging. Am J Clin Nutr 1995; 61: Ross R, Rissanen J, Pedwell H, Clifford J, Shragge P. Influence of diet and exercise on skeletal muscle and visceral adipose tissue in men. J Appl Physiol 1996; 81: Ross R, Leger L, Morris D, de Guise J, Guardo R. Quantification of adipose tissue by MRI: relationship with anthropometric variables. J Appl Physiol 1992; 72: Snyder WS, Cooke MJ, Manssett ES, Larhansen LT, Howells GP, Tipton IH. Report of the Task Group on Reference Man. Pergamon: Oxford, Bjorntorp P. Neuroendocrine perturbations as a cause of insulin resistance. Diabetes Metab Res Rev 1999; 15: Lonnqvist F, Thorne A, Large V, Arner P. Sex differences in visceral fat lipolysis and metabolic complications of obesity. Arterioscler Thromb Vasc Biol 1997; 17: Hayashi T, Boyko EJ, Leonetti DL, McNeely MJ, Newell-Morris L, Kahn SE et al. Visceral adiposity is an independent predictor of incident hypertension in Japanese Americans. Ann Intern Med 2004; 140: Boyko EJ, Fujimoto WY, Leonetti DL, Newell-Morris L. Visceral adiposity and risk of type 2 diabetes: a prospective study among Japanese Americans. Diabetes Care 2000; 23: Kuk JL, Katzmarzyk PT, Nichaman MZ, Church TS, Blair SN, Ross R. Visceral fat is an independent predictor of all-cause mortality in men. Obes Res 2006; 14: Leon AS, Rice T, Mandel S, Despres JP, Bergeron J, Gagnon J et al. Blood lipid response to 20 weeks of supervised exercise in a large biracial population: the HERITAGE Family Study. Metabolism 2000; 49: Boule NG, Weisnagel SJ, Lakka TA, Tremblay A, Bergman RN, Rankinen T et al. Effects of exercise training on glucose homeostasis: the HERITAGE Family Study. Diabetes Care 2005; 28: Pare A, Dumont M, Lemieux I, Brochu M, Almeras N, Lemieux S et al. Is the relationship between adipose tissue and waist girth altered by weight loss in obese men? Obes Res 2001; 9: Kuk JL, Ross R. Measurement of body composition in obesity. In: Kusner RF, Bessesen DH (eds). Treatment of the Obese Patient. Humana Press: Totowa, Kay SJ, Fiatarone Singh MA. The influence of physical activity on abdominal fat: a systematic review of the literature. Obes Rev 2006; 7: Seidell JC, Bjorntorp P, Sjostrom L, Sannerstedt R, Krotkiewski M, Kvist H. Regional distribution of muscle and fat mass in menfnew insight into the risk of abdominal obesity using computed tomography. Int J Obes 1989; 13: Yusuf S, Hawken S, Ounpuu S, Bautista L, Franzosi MG, Commerford P et al. Obesity and the risk of myocardial infarction in participants from 52 countries: a case-control study. Lancet 2005; 366: Kamel EG, McNeill G, Van Wijk MC. Change in intra-abdominal adipose tissue volume during weight loss in obese men and women: correlation between magnetic resonance imaging and anthropometric measurements. Int J Obes Relat Metab Disord 2000; 24: Ross R, Rissanen J, Hudson R. 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 1996; 20: