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Predictors of Body Composition and Body Energy Changes in Response to Chronic Overfeeding

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Predictors of Body Composition and Body Energy Changes in Response to Chronic Overfeeding International Journal of Obesity (2014) 38, 236–242 & 2014 Macmillan Publishers Limited All rights reserved 0307-0565/14 www.nature.com/ijo ORIGINAL ARTICLE Predictors of body composition and body energy changes in response to chronic overfeeding C Bouchard1, A Tchernof2 and A Tremblay3 OBJECTIVE: We have previously shown that 24 young lean men (12 pairs of identical twins) subjected to a standardized 353 MJ (84 000 kcal) overfeeding protocol over 100 days exhibited individual differences in body weight and composition gains. The mean ( þ s.d.) gains in fat mass (FM) and fat-free mass (FFM) were 5.4 þ 1.9 kg and 2.7 þ 1.5 kg for a total body energy (BE) gain of 221 þ 75 MJ, representing 63% of the energy surplus consumed. We report here on the most important baseline correlates of these overfeeding-induced changes with the aim of identifying biomarkers of the response. RESULTS: Baseline maximal oxygen uptake per kg body mass was negatively correlated with gains in weight, FM and BE (all Po0.05). Enzyme activities indicative of skeletal muscle oxidative potential correlated with gains in FM and BE (all Po0.05). Baseline thyroid-stimulating hormone levels in response to thyrotropin-releasing hormone stimulation correlated positively with changes in FM-to-FFM ratio (Po0.05). Plasma concentrations of androstenediol sulfate, dehydroepiandrosterone and 17-hydroxy pregnenolone were negatively correlated with gains in FM and BE (0.01oPo0.05), whereas the level of estrone was negatively correlated and androsterone glucoronide was positively correlated with FFM gains (Po0.05). Baseline leptin and abdominal fat cell size correlated positively with gains in weight, FM and BE (Po0.05). When compared with the six highest BE gainers, the six lowest gainers exhibited higher thermic effect of a meal (TEM) and plasma levels of total testosterone, cortisol, estradiol, androstenedione and androstenediol sulfate (all Po0.05). High baseline levels of total TEM, testosterone and androstenediol sulfate were associated with lower FM gains, whereas high baseline levels of FT4 and estrone were found in low-FFM gainers. CONCLUSION: Although none of the variables exerted individually an overwhelmingly strong influence on overfeeding-induced changes, baseline FFM, maximal oxygen uptake, muscle oxidative capacity, androgens and leptin levels were the most consistent significant biomarkers of the responsiveness to chronic overfeeding. International Journal of Obesity (2014) 38, 236–242; doi:10.1038/ijo.2013.77 Keywords: positive energy balance; biomarkers; long-term overfeeding INTRODUCTION fat accrued relative to lean mass. Importantly, variations in the We have previously reported that there are individual differences FM-to-FFM gains were correlated with the gains in body mass, 1,5 in body mass gain when young adults of normal body weight are with the coefficient reaching 0.61 (Po0.01). Those who gained subjected to a standardized overfeeding protocol,1 a finding that more FM relative to FFM were the high-body-mass gainers, has been subsequently well replicated.2–4 In our own experiment, whereas those gaining relatively more FFM were the low gainers. 24 young lean adult males were exposed to a 353 MJ (84 000 kcal) Human heterogeneity in the response to the much described overfeeding protocol over a period of 100 days while being ‘obesogenic environment’ created by affluent societies represents confined to a sedentary lifestyle.1 The average weight gain was a critical aspect of the obesity epidemic; this environment is often 8.1 kg with an s.d. of 2.4 kg. The average gain in fat mass (FM) was the focus of observational studies but has not been thoroughly 5.4 kg whereas that in fat-free mass (FFM) reached 2.7 kg. investigated experimentally. Although the overfeeding protocol Assuming that the energy content of FM is B38.9 MJ (9300 kcal) conducted with the collaboration of identical twins was focused per kg and that of FFM is 4.3 MJ (1020 kcal) per kg, then a total of primarily on testing the hypothesis that there was a genotype– 222 MJ was recovered on average as body mass changes, overfeeding interaction effect in the response to the caloric representing B63% of the excess energy intake. The FM-to-FFM surplus, we are in the present paper taking advantage of the ratio increased from 0.13 to 0.22 (Po0.001), reflecting the fact extensive panel of pre-overfeeding traits to investigate the most that on average B2 kg of adipose tissues were accrued for each parsimonious predictors of the gains in body mass, FM, FFM and kg of lean mass. total body energy (BE), with a particular focus on the partitioning The gains in FM relative to those in FFM can be seen as an of the energy gains between adipose and lean tissues. indicator of variation in energy partitioning. Thus, although the The identification of biomarkers of body composition changes in average change in the FM-to-FFM ratio was 2:1 in the 100-day response to chronic overfeeding may allow for the early detection overfeeding experiment,1,5 a ratio close to what has been reported of individuals at risk for excess body weight and FM gains. These before,6 there was considerable heterogeneity in the amount of new analyses have the potential to generate new hypotheses 1Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA; 2Department of Nutrition, Laval University, Quebec City, Quebec, Canada and 3Department of Kinesiology, Laval University, Quebec City, Quebec, Canada. Correspondence: Dr C Bouchard, Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA 70808 USA. E-mail: [email protected] Received 18 January 2013; revised 22 March 2013; accepted 4 April 2013; accepted article preview online 20 May 2013; advance online publication, 18 June 2013 Baseline predictors of the response to overfeeding C Bouchard et al 237 about the causes of human heterogeneity in the response to of the highest (N ¼ 6) and lowest (N ¼ 6) gainers with overfeeding were chronic overfeeding. compared by t-test procedures. In all cases, the minimum P-level for statistical significance was set at 0.05. SUBJECTS AND METHODS Subjects RESULTS A total of 24 sedentary young men gave their written consent to As reported previously,1 the 100-day overfeeding protocol caused participate in this study, which was approved by the Laval University Medical Ethics Committee and the Office for Protection from Research significant increases (Po0.0001) in body mass, FM, FFM and total Risks of the National Institutes of Health (Bethesda, MD, USA). These BE (Supplementary Table S1). The average weight gain was 8.1 kg, subjects were members of 12 pairs of identical twins, aged 21±2 years with a range of 4.3 to 13.3 kg. The FM-to-FFM ratio increased from (mean and s.d.). Their origin, medical status and morphological and 0.13 to 0.22 (Po0.0001), indicating that the gains in adipose tissue lifestyle characteristics have been described in an earlier publication.1 were substantially greater than the gains in lean mass. Pre-overfeeding levels of body weight, FM, FFM, BE and daily Experimental protocol caloric intake were not correlated with overfeeding-induced The subjects were studied eight at a time (four pairs of twins) over a period changes with one exception: FFM was negatively correlated with of 18 months. Subjects were housed in a closed section of a dormitory on the changes in the FM-to-FFM ratio (r ¼À0.41; P ¼ 0.05). the campus of Laval University under 24-h supervision. Each subject stayed Interestingly, baseline (weight maintenance) energy intake was in the unit for 120 days, which included a 14-day baseline observation not correlated with any of the changes caused by overfeeding period, a 3-day pre-overfeeding testing period, a 100-day experimental (Table 1). overfeeding treatment and a 3-day post-overfeeding testing period. Resting metabolic rate (RMR) and thermic effect of a meal (TEM) The energy cost of weight maintenance was estimated during the were not correlated with the overfeeding-induced changes in 14-day baseline period. Subjects were instructed to eat normally from body weight, FM, FFM or BE (Supplementary Table S2). The only foods prepared for them and monitored for energy and macronutrient exception was a correlation of 0.45 (P 0.05) between baseline content by dietitians. Body weight was measured daily, and body density À ¼ measurements were obtained on three occasions from a series of TEM over 4 h and the gains in the FM-to-FFM ratio. There was underwater weighing tests. Subjects were kept sedentary except for a no correlation between respiratory quotient during the RMR supervised 30-min daily walk. measurement and at various time points of the TEM test with the During the overfeeding period, subjects were overfed by 4.2 MJ overfeeding-induced gains in body weight, FM, FFM or BE. (1000 kcal) per day over the estimated energy cost of weight maintenance, VO2max (maximal oxygen uptake) per kg of body weight was 6 days a week, for a period of 100 days. On the seventh day of each week, negatively correlated with the gains in body weight, FM and BE, energy intake was rolled back to the pre-overfeeding energy cost of with coefficients ranging from À 0.41 to À 0.49 (all Po0.05; weight maintenance level. The subjects were thus overfed during 84 of the Table 2). Moreover, the overfeeding-induced changes in FM 100 days, for a total excess energy intake of 353 MJ (84 000 kcal). The relative to those in FFM were negatively related to baseline contribution of each macronutrient to energy intake was standardized on a 24-h basis as follows: 15% from protein, 35% from lipid and 50% from VO2max per kg of body weight (r ¼À0.43; Po0.05).
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