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Animal Physiology

Evidence in Female Rhesus Monkeys (Macaca mulatta) that Nighttime Caloric Intake is not Associated with Weight Gain Elinor L. Sullivan,*† Alejandro J. Daniels,‡ Frank H. Koegler,† and Judy L. Cameron*†§¶

Abstract SULLIVAN, ELINOR L., ALEJANDRO J. DANIELS, FRANK H. KOEGLER, AND JUDY L. CAMERON. Evidence in female rhesus monkeys (Macaca mulatta) that nighttime caloric intake is not associated with weight gain. Obes Res. 2005;13:2072–2080. Objective: To evaluate the hypothesis that nighttime consumption of calories leads to an increased propensity to gain weight. Research Methods and Procedures: Sixteen female rhesus monkeys (Macaca mulatta) were ovariectomized and placed on a high-fat diet to promote weight gain, and we examined whether monkeys that ate a high percentage of calories at night were more likely to gain weight than monkeys that ate the majority of calories during the day. Results: Within 6 weeks post-ovariectomy, calorie intake and body weight increased significantly (129 ⫾ 14%, p ⫽ 0.04; 103 ⫾ 0.91%, p ⫽ 0.02, respectively). Subsequent placement on high-fat diet led to further significant increases in calorie intake and body weight (368 ⫾ 56%, p ⫽ 0.001; 113 ⫾ 4.0%, p ⫽ 0.03, respectively). However, there was no correlation between the increase in calorie intake and weight gain (p ⫽ 0.34). Considerable individual variation existed in the percentage of calories consumed at night (6% to 64% total daily caloric intake). However, the percentage of calorie intake occurring at night was not correlated with body weight (r ⫽ 0.04; p ⫽ 0.87) or weight gain (r ⫽ 0.07; p ⫽ 0.79) over the course of the study. Addi-

Received for review March 22, 2005. Accepted in final form October 6, 2005. The costs of publication of this article were defrayed, in part, by the payment of page charges. This article must, therefore, be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Departments of *Physiology and Pharmacology, §Behavioral Neuroscience, and ¶Obstetrics and Gynecology, Oregon Health and Science University, Portland, Oregon; †Oregon National Primate Research Center, Beaverton, Oregon; and ‡Department of Metabolic Diseases, GlaxoSmithKline, Inc., Research Triangle Park, North Carolina. Address correspondence to Judy L. Cameron, Oregon National Primate Research Center, 505 NW 185th Avenue, Beaverton, OR 97006. E-mail: [email protected] Copyright © 2006 NAASO

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tionally, monkeys that showed the greatest nighttime calorie intake did not gain more weight (p ⫽ 0.94) than monkeys that showed the least nighttime calorie intake. Discussion: These results show that eating at night is not associated with an increased propensity to gain weight, suggesting that individuals trying to lose weight should not rely on decreasing evening calorie intake as a primary strategy for promoting weight loss. Key words: monkey, ovariectomy, high-fat diet, body fat, estrogen

Introduction The notion that eating in the evening is more likely to promote weight gain than consuming food at other times of day is popular, and many diets recommend limiting food intake during the evening hours (1–3). Because metabolic rate decreases during periods of sleep in humans (4 –10) and animals (11–15), it seems logical to assume that eating during a time when metabolic rate is slowing may lead to less use of consumed energy and, therefore, more storage of energy and ultimately to weight gain. However, evidence that nighttime eating causes greater weight gain than comparable calorie consumption at other times of day is limited, and data from some studies do not support this conclusion. Several studies find that increased nighttime eating is associated with an increased likelihood of weight gain, but other studies do not support this conclusion. In a group of 15 women, greater weight gain over a 2-week period was reported in those who ate more at night (16). Additionally, several studies find that night shift workers gain more weight and are heavier than individuals who work during the day (17–19). People with nighttime eating syndrome, defined as consuming more than 50% of one’s daily calorie intake at night, have been reported to gain weight more easily than individuals who consume the majority of their calories during the day (20). However, a 10-year study of ⬎7000 people showed no correlation between nighttime food intake and weight gain (21), and several other studies

Nighttime Eating and Weight Gain, Sullivan et al.

have reported no correlation between obesity and nighttime consumption of calories (23,24). Thus, more research is needed to determine whether consuming calories at night actually leads to greater weight gain than consuming the equivalent number of calories during the day. Additionally, several studies report that obese individuals eat a higher proportion of calories at night than lean individuals (22–24). However, in the Waxman and Stunkard study (23), the obese group had a higher total daily calorie consumption, and in the Beaudoin and Mayer study (22), the authors raised concerns regarding possible under-reporting of caloric intake in the obese group. In addition, other studies have not found an association between obesity and nighttime consumption of calories (25,26), and one study found that nighttime eating was associated with leanness (27). Thus, the association between obesity and nighttime food intake is unclear and warrants further investigation. To determine whether individuals who consistently eat at night are more likely to gain weight and/or are heavier than those who predominantly consume calories during the day, we assessed the percentage of daily calories consumed at night in a group of female rhesus monkeys that were placed on a weight gain regimen for a 1-year period. Increased calorie consumption and weight gain have been reported previously after ovariectomy (28 –32) and after high-fat diet consumption (33–38) in numerous species. Thus, we ovariectomized monkeys and placed them on a high-fat diet to promote weight gain. The use of monkeys for this study allowed accurate measurement of caloric intake across the 24-hour day in a species that eat most of their daily calories as daytime meals (39,40), like humans. We found substantial individual variation in both the amount of weight gained and the percentage of calories consumed at night, with some animals eating as much as 65% of their total daily calories at night. However, there was no association between the percentage of total calories consumed at night and probability of gaining weight during this 1-year period.

Research Methods and Procedures Animals Sixteen adult female rhesus monkeys (Macaca mulatta), 7 to 11 years of age, were studied. Animals were used as their own controls; thus, body weight and food intake measurements made throughout the study were compared with the baseline preovariectomy measures for each animal. In addition, because the effects of ovariectomy on body weight have not been well studied in primate species, we added a control group that had ovarian surgery, but were not ovariectomized, to control for the effect of ovarian surgery on weight gain. This control group consisted of 28 adult female rhesus monkeys, 5 to 12 years of age, who underwent a laparoscopic surgery in which ovaries were manipulated but not removed (aspiration of one or more follicles to collect oocytes).

All monkeys were housed in individual stainless steel cages in a temperature-controlled room (24 ⫾ 2 °C), with lights on for 12 h/d (7 AM to 7 PM). Monkeys were fed ad libitum throughout the study. Initially, monkeys were fed two meals a day consisting of 12 high-protein monkey chow biscuits (no. 5047, jumbo biscuits; Ralston Purina Co., St. Louis, MO) at 9:30 AM and 1 PM. In addition, one-half apple was provided at 7 PM. Monkeys had adapted to the diet and living conditions for at least 18 months before initiation of this study. Eight weeks post-ovariectomy, the diet was switched from a low-fat chow diet to a high-fat diet, and meals were provided at 9:15 AM and 3:15 PM. For the low-fat chow diet, 11.32% of the energy was derived from fat (total fat is 27.3% saturated fatty acids, 24.4% monounsaturated fatty acids, and 48.3% polyunsaturated fatty acids). The high-fat diet was formulated following the recipe developed by Clarkson and colleagues (41,42) to study diet-induced atherosclerosis. This diet had 35.3% of the energy derived from fat (total fat is 41.8% saturated fatty acids, 35.6% monounsaturated fatty acids, and 22.6% polyunsaturated fatty acids). Water was available ad libitum throughout the study. The study was reviewed and approved by the Oregon National Primate Research Center (ONPRC)1 Animal Care and Use Committee. Surgery Experimental animals were ovariectomized bilaterally using sterile laparoscopic techniques. Control monkeys also underwent a laparoscopic surgery; however, instead of ovariectomy, control monkeys underwent ovarian follicular aspiration to retrieve oocytes, follicular fluid, and granulosa cells from the ovaries. In preparation for this surgery, control animals received a regimen of Antide (Ares-Serono Inc., Randolph, MA), followed by recombinant human follicle-stimulating hormone to stimulate follicular development (43). Measurement of Body Weight, Caloric Intake, and Body Fat Measurements of body weight, calorie intake, and body fat were made throughout the study in experimental monkeys. Body weight was tracked in control monkeys before and after ovarian surgery. Body Weight and Length Assessments. Experimental monkeys were weighed on the day of ovariectomy and then at weekly intervals. Control monkeys were weighed before and at 1, 2, 4, and 8 weeks after ovarian surgery. Weight measurements were made before consumption of the morning meal, at ⬃8 AM. In experimental monkeys, crown rump 1 Nonstandard abbreviations: ONPRC, Oregon National Primate Research Center; IM, intramuscular; NEAT, non-exercise activity thermogenesis.


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length was measured while animals were sedated with ketamine hydrochloride [10 mg/kg intramuscular (IM)] and were laying flat on their backs with their head against a fixed head rest. BMI was calculated as body weight (kilograms) divided by the square of crown rump length (meters squared). Calorie Intake Assessments. Total food consumption at each meal was recorded throughout the study for experimental monkeys, by counting the amount of food remaining before the next meal presentation. Assessments of nighttime calorie consumption (from 7 PM to 8 AM) were made twice before ovariectomy, twice 7 weeks after ovariectomy, and at weekly intervals during the 9 months of high-fat diet consumption. Before study initiation, we recorded food consumption at 7 AM and 8 AM for 4 days, and there was no significant difference in food consumption during this 1-hour period (t ⫽ 0.72, df ⫽ 15, p ⫽ 0.49; t ⫽ 1.0, df ⫽ 15, p ⫽ 0.33; t ⫽ 1.46, df ⫽ 15, p ⫽ 0.16; t ⫽ ⫺0.44, df ⫽ 15, p ⫽ 0.67 for days 1 to 4, respectively); thus, for this study, overnight food intake was measured from 7 PM to 8 AM. DXA Measurements. Body composition (percentage body fat, total body fat mass, and lean body mass) was determined using DXA at 7 weeks post-ovariectomy and 5 and 9 months after initiation of the high-fat diet in experimental monkeys. Animals were sedated with Telazol (3 mg/kg IM; Fort Dodge Animal Health, Fort Dodge, IA), supplemented with ketamine hydrochloride (10 mg/kg IM), and were positioned supine on the bed of a Lunar DPX scanner (Lunar Corporation, Madison, WI). Total body scans were done in the pediatric medium scan mode with a voltage of 76 kV. Lunar software version 3.4 was used to calculate percentage body fat, fat mass, and lean tissue mass. Two or three scans at each time period were performed per monkey, and averages were calculated. Assays Plasma estrogen, progesterone, and testosterone concentrations were measured using a Roche Elecsys 2010 clinical instrument and assay reagents from Roche Diagnostics (Indianapolis, IN). Assay sensitivities were 10 pg/mL, 0.03 ng/mL, and 0.02 ng/mL, and interassay variabilities were 7.5%, 3.6%, and 4.6% for estrogen, progesterone, and testosterone, respectively. Statistical Analyses Changes in weight and calorie intake are expressed as percentage of preovariectomy levels. The assumptions of normality and homoscedacity were tested for all analyses. The body weight measurements of the control monkeys and the BMI measurements of the experimental monkeys were not normally distributed and could not be transformed; thus, a Friedman Rank Sum Test was used to look for significant differences between multiple measurements, and the Wil2074


Figure 1: Body weight vs. caloric intake before ovariectomy (r ⫽ ⫺0.31, p ⫽ 0.25).

coxon signed ranks test was used to look for differences between pairs of measurements. All other measurements were normally distributed or were normally distributed after a square root transformation. Measurements made multiple times throughout the study were analyzed using one-way repeated-measures ANOVA. If a significant difference was found, planned contrasts were utilized to compare measurements with baseline, using the least significant difference test. Ovarian hormone concentrations before and after ovariectomy and overnight food intake before and after high-fat diet consumption were analyzed using a paired Student’s t test. Correlations between parameters were determined using a Pearson product moment correlation. Comparisons between the top and bottom quartile of monkeys, based on percentage increase in caloric intake or percentage of calories consumed at night, were made with independent Student’s t tests. For all tests, ␣ values were considered significant with p ⱕ 0.05. Data are presented as mean ⫾ SEM. All statistical analyses were conducted using the SPSS software package (SPSS Inc., Chicago, IL).

Results Ovariectomy led to a significant decrease in circulating levels of estradiol (t ⫽ 9.28, df ⫽ 15, p ⬍ 0.001), with no significant changes in mean plasma progesterone or testosterone concentrations. On initiation of the study, individual differences in daily calorie intake (153 to 1128 calories/d) and body weight (4.6 to 9.1 kg) were substantial. However, there was no correlation between caloric intake and body weight (r ⫽ ⫺0.31, p ⫽ 0.25; Figure 1). Caloric intake [F(1.2,18.5) ⫽ 23.17, p ⬍ 0.0001], body weight [F(1.1,16.6) ⫽ 6.52, p ⫽ 0.02], and BMI (␹2 ⫽ 9.42, df ⫽ 3, p ⫽ 0.02) increased significantly over the course of the 1-year study (Table 1). By 6 weeks post-ovariectomy, there were significant elevations in caloric intake (129 ⫾ 14%; p ⫽ 0.04) and body weight (103 ⫾ 0.91%; p ⫽ 0.02) compared with preovariectomy


Table 1. Body composition (mean ⫾ SEM) Baseline Body weight (kg) BMI (kg/m2) Lean body mass (g) Body fat (%) Total body fat mass (g)

6.42 ⫾ 0.31 25.35 ⫾ 1.32

6 weeks after ovariectomy

5 months of high-fat diet

9 months of high-fat diet

6.56 ⫾ 0.28* 25.91 ⫾ 1.17 5317 ⫾ 157 13.28 ⫾ 3.07 956 ⫾ 263

7.23 ⫾ 0.43*† 28.43 ⫾ 1.55*† 5214 ⫾ 158 17.75 ⫾ 3.68 1411 ⫾ 359

7.48 ⫾ 0.52*† 29.37 ⫾ 1.90*† 5080 ⫾ 177† 19.51 ⫾ 4.01 1631 ⫾ 417

* Significant difference from baseline measures. † Significant difference from postovariectomy measures.

levels (Table 1, Figure 2). In contrast, there was no significant change in body weight in the control group that underwent laparoscopic surgery without ovariectomy (␹2 ⫽ 4.32, df ⫽ 3, p ⫽ 0.23). Subsequent placement of experimental monkeys on a high-fat diet caused a further increase in both caloric intake (368 ⫾ 56% of preovariectomy levels; p ⫽ 0.001) and body weight (113 ⫾ 4% of preovariectomy levels; p ⫽ 0.03) within 5 months; both caloric intake and body weight remained elevated throughout 9 months of high-fat diet consumption (Table 1, Figure 2). Despite substantial increases in both caloric intake and weight after ovariectomy and high-fat diet consumption, there was no correlation between the percentage change in body weight and the percentage change in caloric intake (r ⫽ ⫺0.26, p ⫽ 0.34; Figure 3). Moreover, there was no significant difference in body weight gain between the quartile of monkeys that increased their calorie consumption the most over the 1-year period compared with the quartile that increased their calorie consumption the least (t ⫽ 0.12, df ⫽ 6, p ⫽ 0.91). BMI increased progressively with high-fat diet consumption (Table 1), such that BMI was significantly higher than

post-ovariectomy levels after consuming high-fat diet for 5 (p ⫽ 0.03) and 9 (p ⫽ 0.03) months. Lean tissue mass decreased with high-fat diet consumption such that lean tissue mass was significantly lower than post-ovariectomy levels after 9 months of high-fat diet consumption [F(2,26) ⫽ 5.55; p ⫽ 0.01, Table 1]. There was no significant change in either percentage body fat [F(1.2,16) ⫽ 2.5, p ⫽ 0.10] or body fat mass [F(1.2,15) ⫽ 2.7, p ⫽ 0.12] with high-fat diet consumption (Table 1). At the beginning of the study, the mean percentage of total calories consumed at night (percentage nighttime food intake) was 33.7 ⫾ 4.16%; however, nighttime caloric intake of individual monkeys varied from 6% to 64% of total daily caloric intake (Figure 4A). For most monkeys, nighttime caloric intake decreased after 9 months of high-fat diet consumption (t ⫽ 5.62, df ⫽ 15, p ⬍ 0.0001; Figure 4A). Nevertheless, the monkeys that had the highest nighttime food intake at the beginning of the study continued to show the highest nighttime food intake at the end of the study (r ⫽ 0.57, p ⫽ 0.02; Figure 4B). The mean variability in percentage nighttime caloric intake for individual monkeys

Figure 2: Changes in body weight [F(1.1,16.6) ⫽ 6.52, p ⫽ 0.02] (A) and caloric intake [F(1.23,18.47) ⫽ 23.2, p ⬍ 0.001] (B) after ovariectomy and at 5 and 9 months on a high-fat diet. * A significant difference from baseline measures. ⫹ Significant difference from post-ovariectomy measures.


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Discussion

Figure 3: Percent change in body weight and percentage change in caloric intake measured from preovariectomy to after 9 months of high-fat diet consumption (r ⫽ ⫺0.26, p ⫽ 0.34).

over the last 12 weeks of the study was 3.2%. However, there was no indication that monkeys that ate a greater proportion of calories at night were heavier or gained more weight during any part of the study compared with monkeys that ate fewer calories at night. Percent caloric intake at night was not correlated with initial weight (r ⫽ 0.04, p ⫽ 0.87), with weight change after ovariectomy (r ⫽ ⫺0.053, p ⫽ 0.85), with weight change after 9 months on a high-fat diet (r ⫽ 0.06, p ⫽ 0.84), or with weight change over the entire 1-year study period (r ⫽ 0.07, p ⫽ 0.79; Figure 5A). Furthermore, there was no difference in body weight change over the 1-year study period in the quartile of monkeys that consumed the most calories at night vs. the quartile who consumed the least calories at night (t ⫽ ⫺0.74, df ⫽ 6, p ⫽ 0.94; Figure 5B).

Contrary to the hypothesis that nighttime eating is associated with increased weight gain, we found that monkeys eating a large proportion of calories at night did not show an increased propensity to gain weight and were not significantly heavier or fatter than monkeys eating the majority of their daily caloric intake during daytime hours. Moreover, this lack of correlation between percentage caloric consumption occurring in the nighttime and weight gain was seen with weight gain occurring subsequent to ovariectomy and for weight gain resulting from high-fat diet consumption. Before weight gain, a 10-fold variation in the percentage of calories consumed at night by individual monkeys existed, with monkeys consuming from 6% to 64% of their total calories at night. A similar range of nighttime caloric intake, 24% to 65% of total calories, has been reported in humans (21,24,26,27). Additionally, the percentage of calories consumed at night by individual monkeys was highly correlated before and after weight gain, indicating that the percentage of calories consumed at night for each monkey is characteristic of an individual and is consistent over time. Thus, we conclude that the range of nighttime calorie intake in our study was broad enough and stable enough to allow accurate evaluation of whether increased calorie consumption at night is associated with increased body weight or weight gain. Our findings agree with the 10-year study in over 7000 people by Kant et al. (21), which found that nighttime caloric intake was not associated with long-term weight change and several other studies that found no association between obesity and nighttime consumption of calories (25,26). Our results differ from the positive correlation

Figure 4: (A) Percentage caloric intake at night before ovariectomy and after 9 months on a high-fat diet. Bars represent mean percentage caloric intake consumed at night, and the points represent values for individual monkeys. The cross indicates that significant difference between the percentage calories consumed at night before ovariectomy and after high-fat diet consumption (t ⫽ 5.62, df ⫽ 15, p ⬍ 0.0001). (B) Correlation between nighttime calorie intake measured before ovariectomy and after 9 months on a high-fat diet (r ⫽ 0.57, p ⫽ 0.02).

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Figure 5: (A) Percentage nighttime caloric intake (before ovariectomy) vs. weight change over the 1-year study period (r ⫽ 0.07, p ⫽ 0.79). (B) Body weight change over the 1-year study period in the quartile of monkeys that consumed the most calories at night before ovariectomy vs. the quartile who consumed the least calories at night before ovariectomy (t ⫽ ⫺0.74, df ⫽ 6, p ⫽ 0.94).

reported by Keim et al. (16) between weight gain and percentage of calories consumed in the evening in women whom had recently lost weight. However, this was a much shorter term study (i.e., 2 weeks). Our results also differ from those reported in individuals with nighttime eating syndrome, who gained weight more easily than individuals who consumed the majority of their calories during the day (20). However, in addition to not controlling for total calorie consumption in this study, individuals with nighttime eating syndrome have an increased incidence of depression and insomnia (44,45), so differences in propensity to gain weight associated with nighttime eating syndrome could result from factors other than nighttime eating. Our study compared weight gain in animals that have a naturally occurring propensity to eat at night or during the day. An alternative strategy for determining whether eating at night increases the likelihood of weight gain would be to shift naturally occurring eating patterns so that individuals are forced to consume the majority of their calories during the night instead of during the day. A few studies have examined whether eating the largest meal in the morning and the smallest meal at night promotes weight loss. Halberg et al. (46) compared weight loss during a week when six individuals ate an entire 2000-kcal daily allotment of calories as breakfast to a week when those same six individuals ate their entire 2000-kcal daily allotment of calories as dinner and found that individuals lost more weight during the week when they ate all of their calories at breakfast. However, in another study, Armstrong (47) compared weight loss in two groups of dieters, those that received behavior modification (i.e., a dieting strategy) and those that received behavior modification plus shifted the majority of their calorie consumption to the day and found that shifting the timing of calorie consumption did not influence weight loss. We note that the model we have used in our study,

monkeys placed on a controlled feeding regimen, in which food intake can be carefully monitored across the 24-hour day and total caloric intake can be controlled, would be ideal for further examination of whether such a strategy of shifting caloric consumption from the night to the day is effective in promoting weight loss in obese individuals. The results of our study also show that ovariectomy is associated with a rapid increase in caloric intake (29%) and a small, but significant, gain in weight (⬃3%) within the first 2 months post-ovariectomy that was not observed in the control group of monkeys that had ovarian surgery but no ovariectomy. The finding that ovariectomy rapidly increases weight in rhesus monkeys extends numerous previous experiments in small animals (mice, rats, and cats) (48 –51) and one previous report in monkeys (52) that have consistently shown that ovariectomy leads to a 14% to 21% increase in weight within several weeks of ovariectomy. Weight gain, an increase in BMI, and increased adiposity during the menopausal transition in women is also well documented (53–59). However, whether menopausal weight gain results from decreased circulating ovarian hormones, age-related slowing of metabolic rate, or changes in lifestyle (such as a decreased exercise or increased consumption of high-calorie foods), has been debated. The data we present here strongly support the notion that weight gain at menopause, at least in part, results from a decrease in circulating levels of ovarian hormones. As many previous studies in humans (60 – 62) and various animal species (34 –38) have shown, consumption of highfat diet by monkeys caused a dramatic increase in both caloric intake and body weight. Surprisingly, however, we found no association between the change in caloric intake and the change in body weight in response to high-fat diet consumption. A lack of correlation between caloric intake and weight gain or body fat has been observed in human OBESITY RESEARCH Vol. 13 No. 12 December 2005

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populations (24,27,63–71). Nevertheless, changes in caloric intake often correlate with change in body weight in an individual because individuals who decrease their caloric intake generally experience weight loss (72,73). Furthermore, in homogeneous subpopulations, BMI is correlated with caloric intake (74,75). The lack of correlation between caloric intake and body weight in many human studies with people of diverse backgrounds, as well as in our monkey study, is likely to be due to differences in metabolic rate, physical activity, and absorption of nutrients from the gastrointestinal tract among individuals. It is surprising that greater weight gain was not observed in response to the large and sustained increase in caloric intake (368% of baseline levels). The modest weight gain suggests that the monkeys’ homeostatic systems were able to compensate for part of the increase in caloric intake by increasing energy expenditure. Recent evidence in humans suggests that non-exercise activity thermogenesis (NEAT) increases with positive energy balance and that there are large individual differences in the increase in NEAT due to positive energy balance (76,77). In addition, Levine et al. (77) found a correlation between the change in NEAT with the amount of fat gained such that the individuals that increased NEAT the most gained the least amount of fat. Thus, it is would be interesting to measure NEAT in monkeys consuming a high-fat diet and determine whether differences in changes in NEAT would account for the differences in weight gain that we observed. In conclusion, our findings indicate that eating at night is not associated with increased propensity to gain weight. These results suggest that individuals trying to lose weight should not rely on decreasing evening calorie intake as a primary weight loss strategy but should focus on other strategies such as decreasing overall caloric intake and increasing activity level. Our findings also highlight several areas that warrant further investigation, including the role of ovarian hormones in regulating changes in caloric intake and weight at menopause and increasing our understanding of the dramatic individual differences in weight gain in individuals consuming high-calorie diets. We believe that the monkey model that we have utilized in this study, which allows virtually continuous monitoring of food intake and activity and in which the use of metabolic chambers allows accurate assessment of metabolic rate throughout the 24hour day will be very useful in such future studies.

Acknowledgments We thank the Division of Animal Resources at ONPRC for the excellent animal husbandry provided for the monkeys in this study. The assistance of David Hess (Director of the ONPRC Endocrine Services Core Facility) was also greatly appreciated. The monkeys in this study were supported by funds from GlaxoSmithKline, Inc. 2078


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