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Ecological and reproductive variance in serum leptin in wild vervet monkeys.

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AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY 137:441–448 (2008)
Ecological and Reproductive Variance in Serum Leptin
in Wild Vervet Monkeys
Patricia L. Whitten1* and Trudy R. Turner2,3
1
Department of Anthropology, Emory University, Atlanta, GA 30322
Department of Anthropology, University of Wisconsin-Milwaukee, Milwaukee, WI 53201
3
Mammal Research Institute, University of Pretoria, 0002 Pretoria, Republic of South Africa
2
KEY WORDS
adiposity; steroids; energy balance; primates
ABSTRACT
Leptin was originally thought to be an
antiobesity hormone, but increasing evidence suggests
that its ancestral role was to mobilize neuroendocrine
responses to starvation. Research on wild primates is critical for interpreting the high leptin values seen in Western human populations and captive animals. This study
examined natural variation in serum leptin in wild vervet
monkeys (Chlorocebus aethiops), testing the hypothesis
that serum leptin in vervets varies with sex, adiposity,
ecology, and reproductive state. Analyses made use of a
unique dataset comprised of serum and morphometric
measurements obtained from vervet monkeys in four
Kenyan sites differing in altitude, temperature, rainfall,
and access to human foods. Leptin and gonadal steroid
concentrations were analyzed in serum samples from 116
adults. Low leptin levels in males and acyclic females
support the contention that levels seen in captivity are
not typical for wild primates. Measures of adiposity were
not correlated with serum leptin, reflecting the extremely
low fat storage in wild cercopithecine primates. Associations with habitat and season, however, indicate that leptin does register ecological variation in energy balance.
Leptin levels were higher in sites and seasons with
higher rainfall. Moreover, leptin varied significantly with
reproductive state, with higher levels in pregnant than in
acyclic females. Changes in leptin with gestation stage
and duration of lactation suggest that transitory and reversible elevations were an important part of its ancestral
role. These data show that in this wild primate population leptin is a sensitive index of natural variation in habitat and seasonally fluctuating reproductive state. Am J
Phys Anthropol 137:441–448, 2008. V 2008 Wiley-Liss, Inc.
Leptin is a protein produced by adipocytes that regulates food intake and energy expenditure (Zhang et al.,
1994; Friedman and Halaas, 1998; Jéquier, 2002). Leptin
was originally identified as a lipostat and antiobesity
hormone, but subsequent research has cast doubt upon
this characterization (Ahima and Osei, 2004). Although
leptin has profound negative effects on appetite and fat
mass in the rare cases of human mutations in leptin or
leptin receptor genes, it is ineffective in most cases of
the human obesity (Ahima and Osei, 2004; Gale et al.,
2004). This phenomenon, termed leptin resistance, may
result in part from a deficiency in its transport across
the blood-brain barrier (Banks, 2003). The transporter is
saturated at the high serum levels typical of obesity
(30 ng/ml) and is partially saturated even at leptin levels
considered normal in humans (Banks et al., 2000). Only at
leptin levels (1 ng/ml) characteristic of anorexic humans is
the transporter rapid and effective (Banks et al., 2000).
These paradoxical results have been explained by an
evolutionary model positing that the leptin feedback loop
evolved at much lower levels of serum leptin and adiposity than those considered normal in Western human
populations (Banks, 2003; Banks et al., 2006). In this
‘‘Absence of Protection’’ model (Schwartz and Niswender,
2004), an energy dense diet results in obesity because no
mechanisms have evolved to confront a situation (high
leptin levels) that almost never occurred. For example,
anthropologists have shown that the serum leptin levels
are very low and unrelated to adiposity in lean males
from nonWesternized human populations (Bribiescas,
2001; Lindgärde et al., 2004; Kuzawa et al., 2007; Sharrock et al., 2008). U.S. Pima Indians following a Western
lifestyle have four-fold higher leptin concentrations than
Mexican Pima Indians living a more traditional lifestyle
(Fox et al., 1999). On the other hand, only modest
increases (34%) in serum leptin are associated with a
shift from hunting and gathering to agriculture over the
last 30 years in one community of Shuar Amerindian
women (Lindgärde et al., 2004).
The broad range of functions affected by leptin suggest
that leptin may have evolved as a signal of the adequacy
of energy reserves to support costly activities such as
reproduction, pubertal onset, and immune function
(Banks, 2003; Banks et al., 2006). In the language of life
history theory, leptin is a mechanism for enacting optimal
resource allocation rules (Alonso-Alvarez et al., 2007). In
the case of reproduction, this allocation appears to be
accomplished via leptin action on GnRH neurons in the
arcuate nucleus (Chan and Mantzoros, 2001).
However, this model neglects an important piece of the
leptin puzzle. In humans and many other animal species, energy balance and adiposity are not maintained at
a constant set point but rather vary with season, habitat, or reproductive state (Casabiell et al., 2001; Rousseau et al., 2003). The cyclical patterns of energy
C 2008
V
WILEY-LISS, INC.
C
Grant sponsor: NSF; Grant numbers: BCS 0116465, BNS
7703322, BCS 0115993.
*Correspondence to: Patricia L. Whitten, Department of Anthropology, Emory University, 1557 Dickey Drive, Atlanta, GA 30322,
USA. E-mail: antpw@emory.edu
Received 18 February 2008; accepted 19 May 2008
DOI 10.1002/ajpa.20885
Published online 25 July 2008 in Wiley InterScience
(www.interscience.wiley.com).
442
P.L. WHITTEN AND T.R. TURNER
TABLE 1. Vervet monkey life history traitsa
Trait
Infant mortality (proportion/1st year)
Adult female mortality (3–10 year of age)
Fecundity
Age at first birth (years)
Reproductive seasonality (East Africa)
Mating
Births
Weaning age (months)
Interbirth interval (months)
Lifetime reproductive success (number of offspring born)
a
Captive
Wild
0.4
0.0—0.1
0.4–1.1
4.1 (2.5–5)
0.5
0.1–0.2
0.8
4.4–5.7
Aseasonal
Aseasonal
6
10.7 (5.9–24)
0–9
April–Aug
Oct–Dec
12–21
14–21
3.3
Captive data from Fairbanks and McGuire, 1984, 1986; Wild data from Cheney et al., 1988; Whitten, 1982.
TABLE 2. Sites of vervet populations sampled in Kenya
Site
Location
Rainfall (mm)
Elevation (m)
Vegetation
A
B
C
D
Samburu
Mosiro
Naivasha
Kimana
350–400
400–600
>600
200–400
Lowland (650)
Highland (1,500)
Highland (>2,000)
Lowland (1,000)
Dry grassland and thornscrub
Heavily grazed Acacia woodland and savannah
Lakeside grassland, heavily cultivated
Dry grassland and thornscrub
demand and fat storage in reproductively active females
occur without apparent impairment of leptin regulation
and provide an alternative window onto leptin physiology not previously explored outside of the laboratory and
the clinic. Although some studies have examined serum
leptin in nonWestern human populations (Bribiescas,
2001; 2005; Lindgärde et al., 2004; Kuzawa et al., 2007),
none of these studies has examined the influence of the
reproductive state.
Research on wild primates provides a broader context
for investigating the ancestral role of leptin. Levels of serum leptin measured in wild baboons were below 1 ng/
ml, 3–10-fold below the levels seen in captive baboons
and in Western men (Banks et al., 2001, 2003). Leptin
was not correlated with measures of adiposity in wild
baboons, although correlations with BMI and abdominal
fat have been reported in captive macaques (Banks
et al., 2003; Muehlenbein et al., 2005).
These findings support the hypothesis that leptin
evolved to be effective at much lower levels, but other
data suggest that variation in energy availability can alter leptin levels in a natural habitat. Access to a garbage
dump was associated with markedly elevated leptin levels in baboons but only in a subset of males that became
grossly overweight (Banks et al., 2003). Whether these
leptin levels are specific to a human-enriched environment or ever occur in response to variation in natural
habitats is unclear. Similarly, leptin varies with reproductive state in captive primates, where leptin may rise
as much as 25-fold in gestation (Castracane et al., 2005),
but again it is uncertain whether comparable levels are
achieved in wild populations.
The study tested the hypotheses that serum leptin
varies with sex, adiposity, reproductive state, and ecology in wild primates using a unique dataset comprised
of blood samples and morphometrics from four ecologically distinct vervet monkey populations.
MATERIALS AND METHODS
Study site and subjects
The subjects of this study were natural populations of
vervet monkeys (Chlorocebus aethiops) in Kenya, East
American Journal of Physical Anthropology
Africa. In classic life history terms, vervets exemplify a
fast life history (Rowell and Richards, 1979; Fairbanks
and McGuire, 1984; see Table 1). Birth rates are high
when compared with other cercopithecines, and pregnancy and lactation often overlap (Fairbanks and
McGuire, 1984; Horrocks, 1986).
Data and blood samples were obtained in 1978–1979
from four distinct populations of vervet monkeys in
widely separated sites in Kenya, East Africa. The sites
differed in altitude, temperature, and rainfall (Turner
et al., 1997; see Table 2). Site C was surrounded by cultivation, providing access to human food. Wild vervets
from 30 troops were trapped as part of a genetic survey
and blood, hair, dental casts, and morphological measurements were obtained. Hormone immunoassays were
carried out on the serum samples from the adult males
and females for whom sufficient sample volume
remained for assay of leptin and sex steroids. Subsequently, two of the female samples were excluded from
calculation of means and statistical analyses. One anomalous sample with estradiol and progesterone levels typical of the luteal phase and exceptionally high leptin (85
ng/ml) belonged to a female with a 2–3 day old infant.
This profile may have represented either residual hormones of gestation (Hess et al., 1979; Hardie et al., 1997;
Henson and Castracane, 2002) or a postpartum cycle
(Fairbanks and McGuire, 1984) and was excluded as an
extreme outlier. A second sample was excluded because
the female was markedly dehydrated at capture and
lacked a measure of body mass. Exclusion of these two
samples left hormonal and morphometric data from 60
adult females and 56 adult males available for statistical
analyses.
Female reproductive state
Pregnancy and stage of gestation were identified by:
(1) palpation during the physical exam; (2) the presence
of a cystl aminopeptidase variant in a subsample of
females (Turner et al., 1987); (3) serum estradiol and
progesterone (Hess et al., 1979; Eley et al., 1989; Rapkin
et al., 1995).
Females also were classified as lactating or nonlactating by the presence or absence of expressible milk.
443
LEPTIN VARIATION IN WILD VERVETS
The duration of lactation in individual females was estimated by the ages of their presumed infants. Infant ages
were determined by dental eruption patterns (McNamara et al., 1977; Turner et al., 1987). Twenty-six percent
of lactating females were trapped with a clinging infant
who was highly likely to be an offspring. Although vervet females sometimes carry the infants of other mothers, mothers retrieve their infants in competitive feeding
situations like that presented by the baited traps.
Because most infants within a vervet group fell within
the same age range, the stage of lactation in the remaining lactating females was estimated from the modal age
of infants within each group, using age groups of \1
week, 1–6 months, and 6–12 months.
Measures of adiposity
Morphometric measurements were performed by a single member of the field team to ensure consistency. Body
mass was measured on a Sohne baby scale to the nearest
0.5 gm. Trunk length was measured from the external
occipital protuberance to the base of the tail along the
curve of the body (Turner et al., 1997). Adiposity was
estimated using a primate version of the body mass
index, calculated as (kg body mass)/(trunk length m)2.
This measure differs from the human BMI in excluding
the lower limbs from the measurement of body length.
Nevertheless, estimates of BMI in rhesus macaques have
been shown to be highly correlated (r 0.9) with body
fat estimates obtained by isotope dilution (Kemnitz and
Francken, 1986) and dual-energy X-ray absorptiometry
(Eisner et al., 2003).
Hormone assays
Serum samples from the four populations have been
stored together at 2208C to 2808C since they were collected in 1978. A number of studies have demonstrated
the stability of gonadal steroids and protein hormones
like leptin in serum or plasma samples stored at 2208C
for periods as long as 15–29 years (Kley et al., 1985;
Bolelli et al., 1995; Lissner et al., 1999; Laughlin et al.,
2000). Leptin levels in baboon serum stored for 5 years
at 2708C did not differ from the levels in freshly
obtained serum (Banks et al., 2001). Leptin assays of
human serum samples frozen for 29 years yielded the
same correlations with relative weight as in a contemporary sample (Lissner et al., 1999).
Gonadal steroids. Ether extracts of vervet serum were
analyzed for testosterone, estradiol, and progesterone
using modifications of commercial radioimmunoassays as
described earlier (Whitten and Russell, 1996; Whitten
and Turner, 2004). Intra- and inter-assay coefficients of
variation were 5 and 13% for testosterone, 8% and 9–
12% for estradiol, and 9% and 8–12% for progesterone.
Leptin. Vervet serum was assayed for leptin using a primate-specific radioimmunoassay (Linco Research, St.
Charles, MO) that uses I125 human leptin and an antibody to human leptin with 100% cross-reactivity with
nonhuman primate leptin. The assay has a sensitivity of
0.5 ng/ml with 0.1 ml of sample. Samples were diluted
1:2 with diluent and assayed according to the manufacturer’s instructions. Intra- and inter-assay coefficients of
variation were 4–7% and 4–5%.
TABLE 3. Statistics for regression analyses of somatic,
hormonal, and behavioral influences on leptin
Sex and condition
Males (N 5 56)
Body mass
BMI
Order
Testosterone-basal
Testosterone-suppressed
Testosterone-stimulated
Acyclic females (N 5 33)
Body mass
BMI 1 lactation
Order
Estradiol
Duration of lactation
Pregnant females (N 5 25)
Body mass
BMI 1 lactation
Order
Estradiol
Duration of lactation
a
b
Slope 6 SE
R2
P
20.303
20.008
20.187
20.067
0.001
0.001
6
6
6
6
6
6
0.472
0.025
0.097
0.239
0.001
0.000
0.008
0.002
0.064
0.002
0.018
0.230
0.523
0.740
0.059
0.897
0.534
0.032a
0.263
0.025
0.008
20.016
20.101
6
6
6
6
6
0.581
0.028
0.027
0.008
0.022
0.007
0.114
0.003
0.003
0.531
0.654
0.349
0.758
0.758
0.000b
21.743
0.609
0.201
0.037
0.259
6
6
6
6
6
3.057
0.276
0.169
0.014
0.414
0.014
0.242
0.058
0.236
0.061
0.574
0.039a
0.245
0.014a
0.555
P \ 0.05.
P \ 0.001.
Hormonal responsiveness to challenge
In previous work (Whitten and Turner, 2004), we have
shown that the male testosterone responses to anesthesia varied with the sampling order, providing an index of
basal, suppressed, and stimulated testosterone responses
to challenge comparable to the responsiveness measure
introduced by Sapolsky (1991). In contrast to the pattern
of testosterone response, leptin did not show a transient
increase following the anesthesia and did not vary significantly with sampling order (see Table 3). However, its
correlation with testosterone did vary with sample condition. Leptin levels were not correlated with serum testosterone in basal or suppressed conditions, but were positively correlated with the testosterone under the conditions in which the testosterone levels were elevated (see
Table 3). Sampling order had no effect on leptin in acyclic or pregnant females (see Table 3). There were no
effects of sampling order on estradiol. Inclusion of sample order in analyses of other factors did not affect the
results.
Statistical analyses
Statistical analyses of hormone data were performed
using SYSTAT, Version 11. All variables were tested for
normality and homogeneity of variance. Skewed variables were subjected to square root or log transformation
before analysis. In these exploratory analyses, a number
of univariate analyses were performed. The relative
contributions of factors identified as having significant
influences on leptin were investigated further using multivariate analyses. However, sample sizes limited some
comparisons.
RESULTS
Sex differences in serum leptin and body size
Males were larger and heavier than females, and
females varied substantially in body mass across populations, but both the males and females were below the
American Journal of Physical Anthropology
444
P.L. WHITTEN AND T.R. TURNER
TABLE 4. Measures of size and leptin concentrations in adult vervet monkeysa
Trunk length (cm)
Category
Sex (M 5 56; F 5 60)
Reproductive status
Acyclic (N 5 33)
Cycling (N 5 2)
Pregnant (N 5 25)
Population
All females
A (M: N 5 26; F:N 5 21)
B (M: N 5 4; F: N 5 6)
C (M: N 5 10; F: N 5 22)
D (M: N 5 16; F: N 5 11)
Acyclic females
A (F: N 5 10)
B (F: N 5 6)
C (F: N 5 17)
D (F: N 5 0)
Pregnant females
A (F: N 5 11)
B (F: N 5 0)
C (F: N 5 4)
D (F: N 5 10)
Habitat: F: acyclic
Dry (M: N 5 42; F: N 5 10)
Wet (M: N 5 14; F: N 5 23)
a
b
c
Male
Female
Male
Female
41.3 6 0.4b 37.1 6 0.4
4.3 6 0.1b 2.9 6 0.1
37.2 6 0.6
39.0 6 3.0
36.8 6 0.5
2.9 6 0.1
3.5 6 0.1
2.9 6 0.1
39.8
42.0
42.4
42.8
6
6
6
6
0.4c
1.1
1.2
0.8
34.3
37.0
38.9
38.8
6
6
6
6
0.4b
0.9
0.6
0.5
BMI (kg/m2)
Body mass (kg)
4.1
4.2
4.7
4.3
6
6
6
6
0.1
0.4
0.2
0.2
2.5
2.6
3.3
3.1
6
6
6
6
0.1
0.1
0.1b
0.1b
Male
Leptin (ng/ml)
Female
Male
25.0 6 0.4b 21.2 6 0.4 1.1 6 0.2
20.9 6 0.5
23.7 6 4.5
21.4 6 0.5
25.8
23.9
26.2
23.4
6
6
6
6
0.6
1.1
0.9
0.6
21.4
19.2
21.8
20.8
6
6
6
6
0.5
0.5
0.7
1/0
Female
6.2 6 1.3b
1.8 6 0.2
0.9 6 0.1
12.4 6 2.7b
0.7
2.6
2.5
0.5
6
6
6
6
0.1 10.3 6 2.8
1.3b 2.5 6 0.6
0.4b 1.6 6 0.2c
0.1
9.5 6 4.0
1.2 6 0/3
2.5 6 0.6
1.8 6 0.3
18.5 6 3.9
0.7 6 0.4
10.4 6 4.3
0.6 6 0.1
2.5 6 0.4c
1.2 6 0.3
2.0 6 2.6
Values are mean 6 SEM.
Subgroup within category differs significantly from other subgroups in Tukey HSD pairwise comparisons, P \ 0.001.
Subgroup within category differs significantly from other subgroups in Tukey HSD pairwise comparisons, P \ 0.05.
averages reported for captive vervet monkeys (see Table
4). Body mass measurements for acyclic females (2.9 6
0.1 kg) and males (4.3 6 0.1 kg) were significantly (P \
0.001) below the means reported for captive vervet monkeys (females: 5.3 6 0.07 kg; males: 7.2 6 0.1 kg; Kavanagh et al., 2007) and for free-ranging adults in Barbados (females: 3.3 kg; males: 5.3 kg; Horrocks, 1986).
BMI, on the other hand, was higher in adult males
(range: 19–34) than in acyclic females (range: 16–28),
suggesting that it might be measuring lean mass, rather
than fat, in vervet monkey males. BMI levels were substantially lower than the levels reported for captive, nonobese macaque females (28–50: Eisner et al., 2003) or
males (30–40: Kemnitz and Francken, 1986; 46–50:
Muehlenbein et al., 2005) or wild baboons (40–60: Banks
et al., 2003).
As in humans (Casabiell et al., 2001), adult vervets displayed a clear sex difference in serum leptin (see Fig. 1
and Table 4). Serum leptin concentrations were highly
variable in females, and means were significantly higher
than in males although the range of values was similar
in males (0–6 ng/ml) and acyclic females (0–5 ng/ml).
Leptin was not correlated with BMI in either males or
acyclic females (see Table 3). Nor were any significant
correlations observed between leptin and body mass.
However, in pregnant females, leptin was significantly
correlated with BMI when lactation status was included
in the regression (see Table 3).
Leptin and gonadal steroids
The relationship of circulating leptin to gonadal steroids is of interest because leptin both regulates and is
regulated by the hypothalamic-pituitary-gonadal axis. In
this data set, leptin concentration varied with reproductive and hormonal state. Leptin was positively correlated
with serum estradiol in samples from pregnant females
American Journal of Physical Anthropology
Fig. 1. Sex differences in serum leptin levels in wild vervet
monkeys. The plots show median (solid line), mean (dashed
line), 25 and 75 percentiles (box), 10 and 90% (whiskers), and
outliers (points) in male and female vervets.
but was not correlated with estradiol in acyclic females
(see Fig. 2). Inclusion of lactation status did not alter
these relationships. A similar dissociation of leptin from
serum estrogen accords with the data from other lowestrogen subjects such as postmenopausal women (Hong
et al., 2007) and athletes with low body fat (Thong et al.,
2000). A correlation of leptin with estradiol in pregnant
females is not unexpected because both are produced by
the placenta in rising quantities as gestation proceeds.
Acyclic females are in, by definition in this study, a low
estrogen state in which reproduction is not occurring. It
also is a low leptin status that may represent leptin suppression of reproduction in an energy-deficient state.
445
LEPTIN VARIATION IN WILD VERVETS
TABLE 5. Serum leptin concentrations by reproductive
and lactation status
Reproductive Status mean leptin
(ng/ml) 6 SEM (N)
Acyclic
Gestation month
1
2
3
Lactation status
Not lactating
Lactating
Modal lactation
duration months (N)
0.2
6.0
12.0
Fig. 2. Correlation of serum leptin with estradiol concentrations in acyclic and pregnant female vervets.
Leptin and reproductive state
Estradiol and progesterone levels identified 33 females
as acyclic and 25 as pregnant but only two females as cycling (follicular phase). The scarcity of cycling females
may be due to the absence of sampling in April and May,
primary mating months for East African vervets (Struhsaker, 1967; Whitten, 1982).
Leptin varied significantly with the female reproductive state with the higher levels in pregnant than in acyclic females (see Table 4). Like other cercopithecines
(Henson and Castracane, 2002), vervets exhibited
marked increases in leptin early in gestation (F2,22 5
7.410, R2 5 0.402, P 5 0.003), rising to levels as much
as 40-fold higher in the second month.
Lactation
The incidence of lactation varied with reproductive
state (v21 5 4.607, P 5 0.032). Expressible milk was
present in 62% of acyclic females in contrast to 38% of
pregnant females. Leptin declined over the course of lactation. Serum leptin concentration was negatively correlated (b 5 20.101 6 0.081, R2 5 0.518, P 5 0.029) with
the duration of lactation, as estimated by the age of
infants trapped with their mothers. When modal infant
age per group was used as the estimate of the duration
of lactation, leptin was negatively correlated among the
acyclic mothers but not among the pregnant mothers
(see Tables 3 and 5).
Unlike many primate species in which lactation ceases
before conception, 43% of lactating female vervets were
pregnant. ANOVA of reproductive state and the presence
or absence of lactation showed an effect only of reproductive state (F2,55 5 7.852, R2 5 0.271, P 5 0.001).
Site differences
Morphometric measurements showed consistent differences across sites (see Table 4). Turner et al. (1997) have
previously reported site differences in size dimensions
for adult and juvenile males and females using a nested
analysis of variance. Analyses described here were limited to examining size differences in the subset of adults
for which leptin measurements were available. These
analyses confirmed that vervets were larger and heavier
Pregnant
1.2 6 0.5 (8)
17.7 6 3.7 (15)a
16.8 6 0.6 (2)
1.7 6 0.3 (11)
1.8 6 0.2 (11)
13.8 6 3.3 (17)
9.4 6 4.9 (8)
4.6 (1)
2.5 6 0.4 (9)
1.0 6 0.1 (7)a
0.8 (1)
10.6 6 5.4 (7)
a
Subgroup within category differs significantly from other subgroups in Tukey HSD pairwise comparisons, P \ 0.05.
in populations B and C. Trunk length varied significantly across the populations in both the adult males (P
5 0.011) and females (P 5 0.000), with significantly
shorter trunks in population A (male: P 5 0.013; female:
P \ 0.05). Females also differed in body mass across the
populations (P 5 0.000) with heavier animals in the population C (P 0.001). No significant population differences in BMI were observed in males (P 5 0.052) or
females (P 5 0.254).
Male serum leptin varied significantly across the populations with the highest levels in the higher rainfall sites
B (P 0.006) and C (P 5 0.000; see Table 4). No site differences in leptin were observed in acyclic females.
When sites and sexes were combined to compare wet (B
and C) to dry (A and D) habitats, ANOVA showed a significant effect of habitat (F1,85 5 30.781, R2 5 0.409, P 5
0.000) and a significant interactive effect of sex by habitat (F1,85 5 5.915, P 5 0.017) with more marked effects
in males than in acyclic females (see Table 4).
In acyclic females, there also was a significant interactive effect of lactation status with site (F2,27 5 5.322, R2
5 0.391, P 5 0.011). Sites A and B displayed the predicted lower leptin levels in lactating females, but lactating females in Site C had higher leptin levels than nonlactating females (see Fig. 3), perhaps because better
nutrition offered by Site C permitted a more positive
energy balance in lactating mothers.
Seasonal differences
Site differences in leptin might also be attributable to
the seasonal changes in energy availability. The four
populations were sampled at different times of the year,
although there was some overlap of seasons of sampling.
Leptin varied significantly with the month of sampling
in both adult males (F8,42 5 6.297, R2 5 0.588, P 5
0.000) and acyclic females (F6,29 5 2.835, R2 5 0.370, P
5 0.027), varying 4–5-fold over the year. In East Africa,
the rainy seasons are generally in November–December
and March–May, and June–October is the long dry season. Vervet leptin levels were lowest in the long dry season months of June, August, and September and highest
in the rainy season months of November-March, with a
peak in December (see Fig. 4).
American Journal of Physical Anthropology
446
P.L. WHITTEN AND T.R. TURNER
Fig. 3. Site differences in Mean 6 serum leptin in lactating
and nonlactating females.
DISCUSSION
These data support the contention that low leptin levels are more typical for primates than the high levels
observed in captivity and are likely to represent ancestral levels for humans. Serum leptin levels in vervet
males were similar to levels reported for wild baboons
(Banks et al., 2001, 2003) and lean men in nonindustrialized or marginally nourished human populations (Bribiescas, 2001; Kuzawa et al., 2007). Leptin levels were
higher in acyclic vervet monkey females than in males
but still were substantially lower than the levels
reported for captive Old World monkeys (Castracane
et al., 2005) or women in industrialized or Westernized
populations (Bribiescas, 2001; Kuzawa et al., 2007).
Weak correlations of leptin with adiposity in lean
human males, in some marginally nourished populations, have raised questions about leptin’s presumed role
in the regulation of adiposity (Bribiescas, 2001; Kuzawa
et al., 2007). For example, extremely low leptin levels
have been reported for the Tsimané of lowland Bolivia
(Sharrock et al., 2008). Leptin becomes increasingly
coupled to fatness in girls in this population. Adiposity
increases with age, reaching Frisch’s (Frisch and McArthur, 1974) ‘‘critical fatness’’ threshold of 22% by 15
years of age when leptin increases markedly. Boys, on
the other hand, retain a fat level of about 10% and an
extremely low leptin concentration throughout adolescence, suggesting that leptin is a more important signal
of energy availability in females than in males in this
population (Sharrock et al., 2008).
In this study, leptin was not correlated with BMI in
male or acyclic female vervets. Weak correlations of leptin with BMI also have been reported for wild and captive baboon males (Banks et al., 2003; Muehlenbein
et al., 2003). On the other hand, significant correlations of
BMI, abdominal skinfold, and body mass with serum leptin have been reported for captive male rhesus and pigtailed macaques (Muehlenbein et al., 2005). The differences between baboons and macaques in the relation of
leptin to body composition may reflect species differences
in the fat deposition (Muehlenbein et al., 2003). Percent
body fat in wild baboons, estimated from stable isotope
American Journal of Physical Anthropology
Fig. 4. Monthly variation in Mean 6 SEM serum leptin in
males and acyclic females.
dilution, is extremely low (males: 0.8–9.3%; females:
1.9%), reflecting both the leanness of wild baboons and
the very small subcutaneous fat deposits in cercopithecine primates (Altmann et al., 1993). Consequently, individual differences may be below the level of resolution of
the available measures of adiposity (Altmann et al.,
1993).
In marginally nourished populations, factors other
than adiposity play an important role in the regulation
of leptin concentrations (Chan and Mantzoros, 2005).
For example, leptin is a more sensitive and rapid signal
of negative energy balance than of declining adiposity
(Jéquier, 2002). The leptin response to changes in energy
balance is disproportionate to its effect on adiposity
(Ahima and Osei, 2004) and may result in low correlations of leptin with measures of adiposity. For example,
in an intervention study of nine healthy men and
women, a 25% increase in energy intake over energy
expense resulted in a 31% increase in plasma leptin but
an increase in the body mass of only 1% (Hagobian et al.,
2008). Responsiveness to energy balance allows more
immediate energy-saving responses such as increased
feeding, reduced metabolic rate, and amenorrhea (Ahima
and Osei, 2004). In this sample of vervet monkeys, leptin
reflected habitat and seasonal variation in spite of its
low levels. Crop raiding may have contributed to higher
leptin levels in Site C. However, the 4- to 5-fold higher
leptin levels in both sites and seasons with higher rainfall suggest that leptin also registers natural ecological
variation.
As a starvation meter, leptin exerts a permissive influence on reproduction. Falling leptin concentrations with
energy deficit diminish its normal stimulation of GnRH
pulsatility and gonadal steroid secretion (Chan and Mantzoros, 2005). Recombinant human leptin reverses the
starvation response, restoring GnRH and androgen and
estrogen secretion (Blüher and Mantzoros, 2004). These
effects on the HPG axis in energy deprivation states
may explain the varying relationship between leptin and
estradiol observed for pregnant and acyclic females.
Leptin variation with reproductive state in females
shows that very high leptin levels occur in states other
than obesity and are reversible. The highest leptin levels
occur in pregnancy, when leptin rises in maternal circulation due to placental production (Hardie et al., 1997;
LEPTIN VARIATION IN WILD VERVETS
Kratzsch et al., 2000). Placental hormone production
reflects the evolution of maternal-fetal conflict over
resource allocation, a process in which maternal resistance to placental hormones selects for their increased
release (Haig, 1993). These ongoing conflicts have fostered the rapid evolution of growth hormone-related and
prolactin-related genes in the anthropoid primates
(Haig, 2008). For example, the placenta pours out enormous quantities of placental lactogen, independent of
maternal regulation (Haig, 1993). Very high concentrations of human placental lactogen produce leptin resistance by reducing the availability of hypothalamic leptin
receptors (Augustine et al., 2008). Leptin resistance
induces a starvation-like state that stimulates food
intake in spite of increasing fat storage (Kratzsch et al.,
2000; Henson and Castracane, 2002).
After parturition, the high energetic demands of lactation are met by increased appetite and mobilization of
fat reserves (Butte et al., 1997; Dufour and Sauther,
2002; Vernon et al., 2002). The resultant negative energy
balance suppresses leptin, stimulating increased food
intake and reduced energy expenditure. These responses
to reproductive state were evident in wild vervet
females, who displayed dramatic elevations in circulating leptin during gestation and declines over the period
of lactation. In wild populations, high leptin levels
appear to be unique to females, but more work will be
needed to determine if males undergo similar changes in
leptin regulation in other reproductive contexts.
Since leptin was identified in 1994, our view of its role
and action has changed radically. Once thought to be an
antiobesity hormone, leptin is now known to mobilize
key neuroendocrine responses to starvation. It impacts a
broad range of physiological systems: assessing energy
balance, suppressing reproduction and metabolic
expense, mobilizing energy stores, and increasing lipolysis (Chan and Matzoros, 2005). Increasing evidence
shows that leptin indexes not only adiposity but also
energy balance, reproductive activity, and ontogeny. Leptin resistance and responses to energy deficient states
are providing new models for the treatment of reproductive and neuroendocrine abnormalities (Chan and Matzoros, 2005) and have enriched our understanding of the
neuroendocrinology of resource allocation.
CONCLUSIONS
This study addressed the evolutionary model that leptin physiology evolved at much lower levels of leptin and
adiposity than levels found in Western human populations. The model was supported by the low levels of leptin in adult males and females but was contradicted by
significant variation in leptin with habitat, season, and
female reproductive state. This variation shows that predictable elevations in serum leptin were as much a feature of ancestral leptin as low basal levels. An expanded
view of leptin action has demonstrated its involvement
with a range of neuroendocrine factors and axes. A better understanding of the regulation of this variation may
provide insights into the control of obesity and amenorrhea today.
ACKNOWLEDGMENTS
We gratefully acknowledge Dr. N.C. Dracopoli, Dr.
J.G. Else, Institute of Primate Research, and Dr. C.J.
Jolly for their assistance in the early stages of this pro-
447
ject. We are grateful to Mr. Fred Brett for sharing the
serum samples. We thank the Office of the President of
the Republic of Kenya for permission to conduct the original field research in Kenya. We thank Betsy Russell for
her excellent laboratory work. The investigations
described herein comply with the laws of the United
States and Kenya.
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