Reference Body Composition in Adult Rhesus Monkeys: Glucoregulatory and Anthropometric Indices
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Journal of Gerontology: BIOLOGICAL SCIENCES Copyright 2005 by The Gerontological Society of America
2005, Vol. 60A, No. 12, 1518–1524
Reference Body Composition in Adult Rhesus Monkeys:
Glucoregulatory and Anthropometric Indices
Aarthi Raman,1 Ricki J. Colman,2 Yu Cheng,1 Joseph W. Kemnitz,2,3
Scott T. Baum,2 Richard Weindruch,2,4,5 and Dale A. Schoeller1
1
Department of Nutritional Sciences, 2Wisconsin National Primate Research Center, 3Department of Physiology,
4
Department of Medicine, and 5Veterans Administration Hospital, Geriatric Research,
Education and Clinical Center, University of Wisconsin–Madison.
Rhesus monkeys have been used as models to study obesity and disease. The aim of this study
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was to define body mass indices for underweight and obesity in rhesus monkeys. Longitudinal
data collected over 8–14 years from 40 male and 26 female rhesus monkeys were analyzed. Body
weight, insulin sensitivity index, and disposition index were regressed against percent body fat
(%BF). A minimal %BF beyond which further loss of body weight resulted in loss of lean mass
was determined to be 11.5% in older males, 8% in adult females, and 9% in younger adult males.
Insulin sensitivity index and disposition index reached minimum values at 23% fat in older
males, 18% in adult females, and 21% in younger adult males, indicating obesity. The estimated
reference range for %BF was 9%–23% in male and 8%–18% in female monkeys, corresponding
to body mass indices of 32–44 kg/m2 for male and 27–35 kg/m2 for female monkeys.
A DVANCEMENTS in gerontological research have
been promoted through the use of numerous animal
models to identify possible mechanisms of aging and age-
example, obesity in rhesus monkeys has been characterized
using a BW greater than 2 standard deviations (SD) above
the mean for their sex (3) and break-points for percentage
related diseases. Research using nonhuman primates has body fat (%BF), such as 25% BF (10) and 30% BF (11).
provided some valuable information for elucidating the The most important variable that addresses the majority
nature and causes of aging processes observed in humans as of the gluco- and liporegulatory abnormalities in an indi-
well as evaluating potential interventions. Because rhesus vidual is body fat mass (3). Hyperinsulinemia, hyper-
monkeys can develop diet-dependent obesity and diabetes, triglyceridemia, decreased glucose clearance rate, and
they have been highly useful models for discovering anti- glucose disposal can be seen with elevated %BF (12). Too
obesity and antidiabetic treatments. low a %BF, however, may also be detrimental. Higher all-
Monkeys of both sexes with excess body weight (BW) cause mortality rates have been observed in individuals with
due to increased fat mass have been shown to have fasting low BMI (13,14). The increase in mortality rate due to lower
hyperinsulinemia (1), elevated insulin response to intrave- BMI is not fully understood, but factors such as osteoporosis-
nous glucose or marginally impaired glucose tolerance (2), induced fractures (15), decreased vitamin A status [leading
and elevated fasting serum triglycerides (3). These gluco- to decreased survival rates for acute illnesses (16)], and
regulatory and liporegulatory abnormalities are similar to deficient levels of body fat (16) have been suggested as
those of obese humans; nevertheless, there are no uniform possible mechanisms. In addition, a systematic analysis of
definitions for overweight and obesity in rhesus monkeys. the composition of weight loss has shown that mortality
Similarly, large losses of lean body mass can have dele- decreases when the weight loss is due to loss of fat, but
terious consequences such as damage to organs and distur- increases when it is due to loss of fat-free mass (FFM) (17).
bances in cardiac function due to attrition in the myocardial Unfortunately, most of these definitions were not based on
mass (4); however, there are also no uniform definitions of systematic analysis of any metabolic parameters or variables
underweight in rhesus monkeys. This creates an ambiguity in rhesus monkeys in a manner similar to that which has
in the interpretation of results based on the non-uniform been used to define underweight, overweight, and obesity in
definition of underweight, overweight, or obese animals humans making it difficult to compare outcomes between
when used as models for human disease. rhesus monkeys and humans.
In humans, obesity is generally defined as a body mass From the above findings it becomes clear that the
index (BMI) . 30 kg/m2 based on the morbidity risks of relationships between %BF, gluco- and liporegulatory
cardiovascular diseases, hypertension, diabetes, and associ- parameters, and composition of weight loss should be con-
ated symptoms (5–7), and underweight is defined as BMI , sidered to better define obesity and underweight in rhesus
19 kg/m2 (8). In contrast, obesity and underweight in rhesus monkeys. We, therefore, investigated whether various
monkeys has been characterized using morphometric parameters of the metabolic syndrome are associated with
parameters such as BW, BMI, and abdominal circumference %BF and indicate a %BF at which an adult monkey can be
(AC), which are reliable predictors of body fat (3,9). For defined as overweight and/or obese. Also, we investigated
1518REFERENCE BODY COMPOSITION 1519
the relationship between BW and %BF to identify the point 2
BMICRL ¼ ðBW; kgÞ=ðCrown-rump length; mÞ
at which additional loss of weight causes increasing loss of
AC was measured with a non-elastic tape measure to the
FFM. This %BF point can indicate the minimum %BF an
nearest 0.1 cm when the animal was in lateral recumbency
animal should have and hence define underweight. Because
(9,18).
not all primate research institutions may have ready access
to body fat measuring equipment, reference ranges of BMI
will be ascertained using the highly correlated relationship Glucose and Insulin Analysis
of %BF and BMI. AC is highly correlated with visceral Glucose and insulin concentrations were measured annu-
adiposity in humans as well as nonhuman primates (9,18). ally in all the monkeys using frequently sampled intravenous
Studies done on humans have shown that increased abdom- glucose tolerance tests (FSIGT), the methods of which are
inal obesity is associated with increased risk of type 2 detailed elsewhere (23). Briefly, a central venous catheter is
diabetes, cardiovascular diseases, hypertension, and hyper- positioned for administration of the glucose (300 mg/kg BW)
cholesterolemia (19,20). Abdominal adiposity is also asso- and for blood sample collection. To augment insulin response
ciated with hyperinsulinemia, higher plasma glucose and to the bolus of glucose, animals were dosed with tolbutamide
insulin levels, and eventually glucose intolerance which will (5 mg/kg) after the first-phase insulin response. Plasma
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be reflected in the insulin sensitivity. Similar to those of samples collected over a period of 180 minutes were used for
BMI, reference ranges of AC will be ascertained using the measurement of glucose and insulin levels. Plasma glucose
highly correlated relationship of %BF and AC. concentrations were measured using the glucose oxidase
method (Model 23A; YSI, Yellow Springs, OH). Plasma
insulin was measured by double antibody radioimmunoassay
(Linco Research, St. Louis, MO).
SUBJECTS
Longitudinal data from 40 male and 26 female rhesus
monkeys which are part of Wisconsin National Primate Insulin Sensitivity Index
Research Center (WNPRC) were used in this analysis. Glucose and insulin data were analyzed using the minimal
These monkeys are part of an ongoing dietary restriction and model method (24). This model yields a measure of insulin
aging study the protocol for which was reviewed and sensitivity reflecting the ability of insulin to augment the
approved by the Institutional Animal Care and Use Commit- effect of hyperglycemia in promoting glucose uptake and
tee of the Graduate School at the University of Wisconsin inhibiting hepatic glucose output by insulin (24,25). Basal
(21). Data consisted of 639 values from 66 animals (34 insulin (Ib) and glucose (Gb) levels, glucose disappearance
calorie restricted and 32 control) over a span of 14 years in rate (KG), first-phase (acute) insulin response (AIR), second-
older animals and 8 years in adult animals. Monkeys were phase insulin response, and tolbutamide-induced insulin
caged individually in standard stainless steel cages with response are calculated by this model and are then used to
food containers attached to the cages and provision for deduce the insulin sensitivity index (SI). Disposition index
drinking water in each cage. The cages had inside dimen- (DI) was calculated as the product of first-phase AIR and SI,
sions of 89 cm width, 86 cm depth, and 86 cm height. Room and indicated the compensatory adaptation to insulin resis-
temperature was maintained at 218C, and the animals were tance which is a measure of b-cell function.
maintained on a 12-h light/dark cycle with lights on between
6 AM and 6 PM. Animals were fed a semipurified diet Cholesterol and Triglycerides
(Teklad, Madison, WI) containing 15% lactalbumin, 10% Fasting triglycerides (TGb) were measured using the
corn oil, and ;65% carbohydrate. Additional details about enzymatic colorimetric method with glycerol oxidase and
the study have been published elsewhere (21,22). 4-aminophenazone (COBAS INTEGRA; Roche Diagnos-
tics, Indianapolis, IN) with a between-day coefficient of
variation (CV) of 1.9%. Fasting total cholesterol levels were
measured using the enzymatic colorimetric method with
METHODS
cholesterol esterase and 4-aminoantipyrine at an absorbance
of 512 nm (COBAS INTEGRA; Roche Diagnostics) with a
Body Composition
between-day CV of 1.9%.
Whole body composition was measured semiannually
using dual energy x-ray absorptiometry (DXA, Model DPX-
L; GE/Lunar Corp., Madison, WI). Briefly, animals were Statistical Analysis
sedated with a mixture of ketamine–HCl (10 mg/kg BW, Because age had a significant univariate relationship with
IM) and xylazine (0.6 mg/kg BW, IM) for additional %BF (2% increase with age; p , .0001), monkeys were
muscular relaxation (18). categorized based on sex and age range. The males were
divided into younger adult males (AM; mean current age:
18.5 6 3 years; range: 15–22 years) and older males (OM;
%BF ¼ ðFat mass; kgÞ=ðBW; kg ½DXAÞ100 mean current age: 23.2 6 2 years; range: 22–28 years); the
adult females (AF; mean current age: 19.5 6 2 years; range:
BMI of rhesus monkeys was calculated by dividing BW by 17–23 years) were similar in age to AM. Animals were
the square of the crown-rump length (CRL) of the animal. studied based on the groups of the main study of calorie
Crown-rump length was measured with the monkey supine restriction. Data consisted of 639 values from 66 ani-
on a calibrated rule with a fixed headrest. mals over a span of 14 years in OM [(n ¼ 24; N ¼ 297),1520 RAMAN ET AL.
Table 1. Group Characteristics (Mean 6 SD)
Variable Units OM AF AM
Weight kg 11.9 6 3a 8.3 6 2b 11.9 6 2a
Body fat kg 2.9 6 2a 1.9 6 1b 2.4 6 2a
Body fat % 21.5 6 10 19.9 6 11 17.9 6 9
Body mass index kg/m2 42.0 6 9a 34.6 6 7b 41 6 7a
Abdominal
circumference cm 51.0 6 11a 45.6 6 9b 50.1 6 10a
Basal glucose level mmol/L 3.4 6 0.4a 3.4 6 0.4a 3.6 6 1.2b
Basal insulin level pmol/L 285 6 289 254 6 274 205 6 195
Glucose
disappearance rate % 6.4 6 3a 10.2 6 5y 7.3 6 4c
Insulin sensitivity 105/min1/
index (pmol/L) 4.6 6 4a 7.1 6 6b 5.7 6 5a
1
Disposition index min 377 6 282 760 6 491 526 6 360c
a b
Fasting triglycerides mmol/L 1.5 6 1.4ay 1.1 6 0.8a 2.0 6 5b
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Plasma cholesterol mmol/L 4.7 6 0.9a 4.9 6 0.9ab 5.1 6 2.4b
Notes: a,b,cGroups with different letters are significantly different ( p , .05).
SD ¼ standard deviation; OM ¼ older males; AF ¼ adult females; AM ¼
adult males.
n ¼ number of animals; N ¼ number of values from ‘n’
animals] and 8 years in AF (n ¼ 26; N ¼ 219) and AM (n ¼
14; N ¼ 123). Data are presented as mean 6 SD with
a significance level of p , .05.
To define the %BF values that correspond to obese, we
regressed %BF onto each of SI, DI, Ib, TGb, and cholesterol
levels and sought to identify a break-point in the curvilinear
relationships. Similarly, the minimum %BF was ascertained
by regressing %BF onto BW and trying to identify the break-
point in the curvilinear relationship. Break-point analysis was
performed using the statistical software ‘R’ (version 2.0.0;
Free Software Foundation, GNU project), which identified
the point at which the relationships between variables
became insignificant (i.e., slope not different from zero).
RESULTS
The data used for this analysis are from an ongoing study,
and each animal has multiple representations in this data set Figure 1. Relationship between % body fat (%BF) and insulin sensitivity
index (SI) in old male (OM) (A), adult male (AM) (B), and adult female (AF)
with the OM measured for 14 years and the AF and AM (C) monkeys. Symbols represent data from individual animal collected over an
measured for 8 years. The characteristics of the animals are 8-year (AF and AM) or 14-year (OM) period. The exponential regression lines
summarized in Table 1. Within males, the OM and AM of animals which were significant ( p , .05) are shown in the insets.
differed in KG, Gb, DI, plasma cholesterol, and TGb. Female
monkeys were significantly different from males (OM and break-points for maximum attainable %BF before its SI
AM; p , .0001) in their BW, BF (kg), BMI, AC, and SI. becomes minimal were 23.2% in OM, 20.8% in AM,
Basal glucose concentrations (Gb) were significantly higher and 17.5% in AF monkeys. DI also showed an
in the AM compared to the OM and AF ( p , .0007), but exponential relationship with %BF in male (AM, %BF
basal insulin levels were not different among the three ¼ 26.67 * e(0.001 * DI), p , .001; OM, %BF ¼ 26.025 *
groups. TGb was lower in AF than in AM but was not e(0.001 * DI), p , .001) and female (%BF ¼ 22.819 *
different from the OM monkeys, whereas cholesterol levels e(0.0004 * DI), p , .001) monkeys. Accordingly, the %BF
were higher in AM than in OM. These findings prompted us break-points for DI were 23.2% in OM, 22% in AM, and
to stratify the analysis according to age range and gender for 16.4% in AF monkeys. In a regression plot of %BF
the analyses that follow. against SI, AM and OM showed a similar increase in SI
Break-points in the relationships between %BF and SI and with decreasing %BF compared to AF. The mean
DI were at a point of change in slope between the dependent difference in %BF among all three groups was signifi-
and independent variables. When %BF was regressed with cantly different at any given SI (OM and AM ¼ 3.5%, AF
SI, an exponential relationship was observed in male (OM, and AM ¼ 2.1%, and OM and AF ¼ 1.5%; p , .05).
%BF¼ 28.216 * e(0.091 * SI), p , .001; AM, %BF¼ 23.694 * However, for a given %BF, females had higher absolute SI
e(0.08 * SI), p , .0001) and female monkeys (%BF ¼ 26.12 * values than males. At a mean value of 5.7 SI units, the
e(0.067 * SI), p , .001) (Figure 1). Using the R software, the average %BF was 20% in OM and 18% in AM versusREFERENCE BODY COMPOSITION 1521
Table 2. Correlation of Systemic Metabolic Indices
Gb, Ib, AIR, Cholesterol,
% Fat KG mmol/L pmol/L pmol/L mmol/L
OM
KG 0.49
Gb, mmol/L 0.36 0.19
Ib, pmol/L 0.37 0.21 0.25
AIR, pmol/L 0.35 0.09 0.05 0.51
Cholesterol, mmol/L 0.04 0.05 0.06 0.01 0.21
TGb, mmol/L 0.39 0.31 0.11 0.59 0.46 0.18
AM
KG 0.61
Gb, mmol/L 0.24 0.24
Ib, pmol/L 0.49 0.35 0.14
AIR, pmol/L 0.27 0.01 0.26 0.43
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Cholesterol, mmol/L 0.03 0.15 0.38 0.09 0.19
TGb, mmol/L 0.18 0.23 0.48 0.24 0.14 0.87
AF
KG 0.40
Gb, mmol/L 0.24 0.21
Ib, pmol/L 0.28 0.17 0.36
AIR, pmol/L 0.37 0.02 0.18 0.41
Cholesterol, mmol/L 0.07 0.11 0.06 0.16 0.23
TGb, mmol/L 0.44 0.27 0.07 0.27 0.36 0.00
Note: SD ¼ standard deviation; KG ¼ glucose disappearance rate; Gb ¼ basal
glucose level; Ib ¼ basal insulin level; AIR ¼ acute insulin response; TGb ¼
fasting triglycerides.
21.3% in the AF monkeys. Using the interaction between SI and
group, this difference proved to be significant ( p , .0001).
However, there was no significant effect of age on the
relationship of SI and %BF (interaction of SI 3 Age) when
animals in individual groups were analyzed. Also, when the
males were grouped together there was no significant interaction
between SI and age on %BF indicating that age in this group of
animals does not affect the relationship between SI and %BF.
Besides SI and DI, TGb and cholesterol levels and
additional indices of glucoregulation, KG, AIR, Ib, and Gb
levels were examined for any associations with %BF (Table Figure 2. Relationship between % body fat (%BF) and body weight (BW) in
2). Though Gb, Ib, TGb, and cholesterol levels showed old male (OM) (A), adult male (AM) (B), and adult female (AF) (C) monkeys.
similar relationships with %BF, a break-point analysis using Symbols represent data from individual animal collected over an 8-year (AF and
these variables did not reach significance due to a high AM) or 14-year (OM) period. The exponential regression lines of animals which
were significant (p , .05) are shown in the insets.
variability in the data. Hence these variables did not
contribute to the determination of the maximal body fat level.
The lower end of the range for %BF was ascertained negative health-related outcomes even with slight decreases
using the relationship between BW and %BF. The %BF in body fat. It is therefore prudent to add a safety factor to the
of male monkeys showed an exponential relationship with low-end break-point. Based on a comparison of %BF
their BW (OM, %BF ¼ 2.49 * e(0.168 * BW), p , .001; measurement between DXA and total body water, we cal-
AM, %BF ¼ 1.03 * e(0.225 * BW), p , .001) and female culated a mean difference of 3% for the determination of
(%BF ¼ 1.02 * e(0.335 * BW), p , .001). Percent BF was %BF and used this as the safety level needed on the lower
regressed with BW sequentially to identify the break-point end of reference %BF. In so doing, the minimal %BF
where the relationship indicates most of the weight loss as FFM below which animals can be classified as underweight were
(Figure 2). The minimum %BF an animal should have before 11.5% in OM, 9% in AM, and 8% in AF monkeys.
increasing loss of lean body mass occurs was ascertained to be The %BF values can also be translated to BMICRL.
8.5% in OM, 6% in AM, and 5% in AF monkeys. Percent BF showed significant correlations with BMI in all
The above break-point analysis does not provide a measure three groups of monkeys (%BF ¼19.3 þ 0.97 * BMI; r2 ¼
of statistical range around the break-point values. The 0.7, p , .0001 in OM; %BF ¼29.2 þ 1.4 * BMI; r2 ¼ 0.8,
values, therefore, have limitations. There may be individual p , .0001 in AF, and %BF ¼30.7 þ 1.2 * %BF; r2 ¼ 0.8,
variation among animals, and the measurement of %BF may p , .0001 in AM; Figure 3) with the mean %BF (mean 6
not be exact. In either case, animals at the lower end of the SD) at 21.5 6 10% in OM, 19.9 6 11% in AM, and 17.9 6
reference body fat spectrum could be at a greater risk for 9% in AF monkeys. Hence a reference BMI of 32–44 kg/m21522 RAMAN ET AL.
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Figure 3. Relationship between % body fat and body mass index (BMI) in Figure 4. Relationship between % body fat and abdominal circumference
older male (OM, closed triangles), adult female (AF, open squares), and adult (AC) in older male (OM, closed triangles), adult female (AF, open squares), and
male (AM, plus symbols) monkeys. Percent body fat showed significant cor- adult male (AM, plus symbols) monkeys. Percent body fat showed significant
relations with BMI in all three groups of monkeys (% body fat ¼19.3 þ 0.97 * correlations with AC in all three groups of monkeys (% body fat ¼11.9 þ 0.66 *
BMI, r2 ¼ 0.7, p , .0001 in OM; % body fat ¼29.2 þ 1.4 * BMI, r2 ¼ 0.8, p , AC, r2 ¼ 0.6, p , .0001 in OM; % body fat ¼29.5 þ 1.08 * AC, r2 ¼ 0.8, p ,
.0001 in AF; % body fat ¼ 30.7 þ 1.2 * %BF, r2 ¼ 0.8, p , .0001 in AM). .0001 in AF; % body fat ¼ 24.9 þ 0.9 * AC, r2 ¼ 0.9, p , .0001 in AM).
in the AM, 34–44 kg/m2 in OM, and 26–38 kg/m2 in AF cesses in the body. A lower %BF has been associated with
monkeys was deduced. better glucose regulation and better insulin sensitivity (29).
Similarly, these break-points can be translated to AC values. Significant correlations between basal and stimulated insulin
Because %BF and AC have a linear relationship (%BF ¼ levels with various indices of obesity have been noted in
11.9 þ 0.66 * AC; r2 ¼ 0.6, p , .0001 in OM; %BF ¼ monkeys (2,9) and humans (30,31). Hyperinsulinemia has
29.5 þ 1.08 * AC; r2 ¼ 0.8, p , .0001 in AF, and been shown to occur as one of the initial consequences of
%BF ¼ 24.9 þ 0.9 * AC; r2 ¼ 0.9, p , .0001 in AM), increased BW or body fat (32). In fact, this relationship has
we estimated a reference AC of 40–54 cm in AM, 35–53 cm been best reported in monkeys with body fat greater than
in OM, and 35–44 cm in AF monkeys using the reference 30% of their BW (33,34). Conversely, a reduction in BW
range of body fat (Figure 4). or body fat has been shown to decrease insulin dosage or
eliminate the need for supplemental insulin in type 2 diabetics
DISCUSSION (35,36). Hence, we used insulin sensitivity and disposition
Using glucoregulatory indices and changes in body indices to identify the upper end of reference %BF.
composition, we developed a reference range of %BF Hypertriglyceridemia and hypercholesterolemia have
a monkey can have before being classified as underweight been observed in obese humans (37) and nonhuman pri-
or overweight and obese. Insulin-sensitivity measures and mates with higher %BF (3,9), but we were unable to find
changes in FFM during weight change have been used to a break-point associated with these variables. Perhaps this is
identify the reference range for %BF; hence, these data because there is a strong genetic component to the elevated
promise to be a good index to define health using a group of plasma triglycerides (32,38). This genetic component may
metabolic predictors in young and old rhesus monkeys. This have obscured the break-points, wherein the fasting tri-
is an effort in classifying rhesus monkeys into underweight, glyceride and total cholesterol levels were higher in animals
reference, and obese based on their %BF and will make it with higher body fat but were highly variable (CV was 0.3
easier to compare health outcomes with humans. for plasma cholesterol and 1.9 for TGb). Nonetheless, the
The linear relationship between BMI and body fat can be mean TGb levels in the male and female monkeys with
used effectively to ascertain the %BF of an individual based a reference %BF was 1.1 6 0.9 mmol/L and 0.7 6 0.4
on their BMI. However, this relationship needs to be analyzed mmol/L, respectively, compared to 2.7 6 5 mmol/L and
with caution, because a higher BW can be due to a higher lean 1.4 6 0.9 mmol/L in obese animals (p , .001). The levels
body mass, in which instance using BMI may lead to seen in reference %BF animals were within the ranges de-
misclassification of the individual as overweight or obese. fined for humans (39).
Nonetheless, BMI has been used effectively to assess obesity
and underweight in numerous human studies (26–28). Overweight Versus Obese
The relationship between %BF and glucoregulatory
Overweight and Obesity indices was exponential and could not be used to
The literature is replete with evidence of body fat being differentiate between overweight and obese monkeys.
strongly associated with most of the glucoregulatory pro- Nonetheless, obesity is associated with hyperinsulinemia,REFERENCE BODY COMPOSITION 1523
Table 3. Characteristics of Monkeys When Assigned to Underweight, Underweight with Minimal Body Fat
Normal, and Obese Categories (Mean 6 SD) On the other end of the spectrum of body fat, we
Weight, Body Gb, I b, TGb, Cholesterol, identified a minimal %BF to define reference or normal
Variable kg fat, % mmol/L pmol/L mmol/L mmol/L weight of ;10% in male and 8% in female rhesus monkeys.
Males There are, however, few studies in literature that provide
Underweight 8.8 6 1a 5 6 1a 3.1 6 0.3a 90 6 48a 0.6 6 0.3a 4.6 6 1a data against which we can compare these values. One study
Normal 10.7 6 2b 16 6 5b 3.4 6 0.4b 200 6 144b 1.1 6 1a 4.7 6 1a by Altmann and colleagues (41), however, reported that
Obese 14 6 2c 29 6 5c 3.6 6 1c 372 6 337c 2.8 6 5b 5.2 6 2b
young adult baboons foraging in the wild had %BF as low
Females
as 2% (in adult females) and 1% (in adult males).
Underweight 5.9 6 1a 4.2 6 0.5a 3.1 6 0.3a 133 6 118a 0.6 6 0.2a 4.5 6 1a
Normal 7.0 6 1b 10 6 3.9b 3.4 6 0.4b 164 6 107a 0.7 6 0.4a 5.1 6 1b
Anthropometric data indicated that, despite their lower
Obese 9.3 6 1c 27 6 6.2c 3.5 6 0.5b 319 6 324b 1.4 6 1b 4.9 6 1b %BF, growth among the female baboons continued and that
Notes: a,b,cDifferent letters indicate significant differences between un-
the animals maintained reproductive function. This might
derweight, normal, and obese groups within males and females ( p , 0.05). indicate that our minimal %BF values were too conserva-
SD ¼ standard deviation; Gb ¼ basal glucose level; Ib ¼ basal insulin level; tive; however, caution should be maintained when compar-
TGb ¼ fasting triglycerides. ing our data to animals under free-living conditions, due to
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the high fiber content of the diet and the high activity level
of the free-living animals compared to our caged animals.
Both of these factors could differentially influence the
insulin resistance, and glucose intolerance (11). It has been relationship between SI and %BF.
shown that animals with increasing body fat may gradually Despite the data on %BF in wild animals, we were
become diabetic after going through a sequence of events concerned about using minimal %BF obtained by break-
of normoglycemia–normoinsulinemia, normoglycemia– point analysis to define underweight. This concern stemmed
hyperinsulinemia, and hyperglycemia–hyperinsulinemia. With from the rapid weight loss and loss of FFM that was
regard to this sequence, there are two diabetic monkeys in observed when some animals neared but were still above
the larger study cohort that were not included in this these critical values and the potential for serious negative
analysis. The %BF of these two animals was 34.2% and health outcomes that could accompany the loss in FFM
37.6% at the time of diagnosis. In addition, Gresl and (13,14). This concern was amplified by the knowledge that
colleagues (1) reported one additional animal in the larger the measurement of %BF is accompanied by a measurement
study that has since died and was not included in the current error, and thus when the break-point values are applied to
data analysis (this animal became diabetic and had a %BF of individual animals, %BF might be overestimated and the
36% at the time of diagnosis). In our analysis, we concluded animal could be at risk of being underweight despite an
that the maximum body fat a male animal could have before apparently normal %BF. Because of these two factors, we
SI became minimal was ;22% of BW. Hence, we added a safety margin of 3% to the %BF in an effort to
conjecture that male animals with %BF between 22% and reduce the risk in individual animals.
36% can be categorized as overweight, above which we see Finally, it should be noted that our data were derived
more animals with frank diabetes. from animals that were part of a long-term dietary
The findings of Hotta and colleagues (40) can be restriction study. Thus, there was a possibility that the
compared with ours. Hotta and colleagues grouped a cohort relationships between %BF and the other variables in the
of rhesus monkeys according to their fasting plasma insulin diet-restricted animals were a little different from general
and glucose levels using a priori values to characterize the colony animals. No interactions between dietary treatment
animals as lean (normal) hyperinsulinemic or diabetic and the parameters used for the above analyses were
(obese). They reported that the ‘‘normal weight’’ monkeys observed, however; thus we conclude that these values to
in their study had a mean %BF of 18.1 6 3.3% and normal define underweight, overweight, and obesity are reasonable.
fasting plasma glucose and insulin concentrations. The male By using these cut-offs to define nutritional status in rhesus
monkeys in our data set with a ‘‘reference’’ %BF (,22%; monkeys, comparison of studies between those conducted
mean ¼ 16 6 4.5%) were also normoglycemic (3.4 6 0.4 in rhesus monkeys with those conducted in humans should
mmol/L) and normoinsulinemic (200 6 143 pmol/L); these be easier.
values are comparable to those of the animals of Hotta and
colleagues (40) (Table 3). The obese group of Hotta and
colleagues had a mean %BF of 32.6 6 2.7% and were ACKNOWLEDGMENTS
hyperinsulinemic but normoglycemic, thus paralleling our This work was supported by grants P01 AG-11915 (to R. Weindruch)
data in the animals above the upper %BF break-point. and P51 RR000167 (to the Wisconsin National Primate Research Center,
Among the obese group reported by Hotta and colleagues University of Wisconsin, Madison). This research was conducted in part at
(40), noninsulin-dependent diabetes mellitus was observed a facility constructed with support from Research Facilities Improvement
Program grant numbers RR15459-01 and RR020141-01.
in a group of monkeys with mean %BF 35.1 6 4%, similar
We gratefully acknowledge the excellent technical assistance provided
to the three diabetic animals in our larger study. These data by J. A. Adriansjach, C. E. Armstrong, and the animal care and veterinary
support our conjecture on classifying overweight rhesus staff of the Wisconsin National Primate Research Center.
monkeys as 22–34%BF and obese rhesus monkeys as Address correspondence to Dale A. Schoeller, PhD, UW-Madison,
35%BF, although further evidence is needed because the Department of Nutritional Sciences, 1415 Linden Drive, Madison, WI
number of animals on which this is based is still small. 53706. E-mail: dschoell@nutrisci.wisc.edu1524 RAMAN ET AL.
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