Publications

OBJECTIVE: The common marmoset as a model of early obesity was assessed. The hypotheses that juvenile marmosets with excess adipose tissue will display higher fasting glucose, decreased insulin sensitivity, and decreased ability to clear glucose from the blood stream were tested.

DESIGN AND METHODS: Normal and obese (body fat > 14%) common marmoset infants (N = 39) were followed up from birth until 1 year. Body fat was measured by quantitative magnetic resonance. Circulating glucose was measured by glucometer and insulin, adiponectin, and leptin by commercial assays. The quantitative insulin sensitivity check index (QUICKI; a measure of insulin sensitivity) was calculated for subjects with fasting glucose and insulin measures. Oral glucose tolerance tests (OGTTs) were conducted at 12 months on 35 subjects.

RESULTS: At 6 months, obese subjects already had significantly lower insulin sensitivity (mean QUICKI = 0.378 ± 0.029 vs. 0.525 ± 0.019, N = 11, P = 0.003). By 12 months, obese subjects also had higher fasting glucose (129.3 ± 9.1 mg/dL vs. 106.1 ± 6.5 mg/dL, P = 0.042), and circulating adiponectin tended to be lower (P = 0.057). Leptin was associated with percent body fat; however, birth weight also influenced circulating leptin. The OGTT results demonstrated that obese animals had a decreased ability to clear glucose.

CONCLUSIONS: Early-onset obesity in marmosets results in impaired glucose homeostasis by 1 year.

While much is known about adult obesity in nonhuman primates, very little is known regarding development of childhood adiposity. As small monkeys that are easy to handle and have a relatively fast life history, common marmoset monkeys (Callithrix jacchus) offer interesting opportunities to examine the question of fat versus lean mass growth in a nonhuman primate. This article provides an overview of our understanding of early life growth in mass in marmoset monkeys, based primarily upon our past 20 years of research, culminating in our recent findings on early life obesity in this species. Common marmosets display variance in early life growth patterns that is related to both pre- and postnatal factors and the marmoset uterine environment is exquisitely designed to reflect resources available for the gestation of multiple offspring, making them an interesting model of developmental programming. We have demonstrated that obesity can be generated in very early life in captive marmosets, with excess adiposity evident by one month of age, making this species a potentially valuable model in which to study pediatric obesity and its sequelae. Birth weight is associated with adiposity in animals vulnerable to obesity. Early life exposure to higher fat diets enhances the chances of postweaning obesity development. However, overall higher food consumption is also associated with obesity development at later ages. One unexpected finding in our studies has been the relatively high body fat percentage of neonatal (12-18%) marmosets suggesting that hypotheses regarding the uniqueness of high human neonatal adiposity merit further examination.

The ability to measure and interpret variables associated with feeding behavior and food intake is essential to a variety of nonhuman primate study modalities. The development of a technique to accurately and efficiently measure food intake and meal patterning in captivity will enhance both the interpretation of foraging behavior in the wild as well as our ability to model clinically relevant human feeding pathologies. In this study, we successfully developed the use of a rodent lickometer system to monitor meal patterning in captive common marmosets. We describe the modifications necessary for this type of instrumentation to be used successfully with marmosets. We define variables of interest that relate to both previous rodent literature and human clinical measures. Finally, we relate our findings to potential translational value for both primate field research and biomedical applications.

Characterizing the phenotypic changes associated with aging in a short-lived primate is necessary in order to develop better translational models for human health, aging, and disease research. A population of conventionally housed marmoset monkeys was assessed to determine if phenotypes of body composition, hematology, and morphometrical measures were associated with age or risk of death. We found that the cause of mortality in older marmosets was more likely to be due to cardiac and chronic kidney disease than in younger marmosets. Older marmosets have decreased fat mass, morphometric measures, and serum albumin. Older marmosets are more likely to show a modified posture while at rest and this modified posture was significantly associated with an increased risk of imminent death. These assessments provide an initial definition of aged health in marmosets and a base for future translational aging research with this species.

Animal models to study the causes and consequences of obesity during infancy in humans would be valuable. In this study, we examine the patterns of fat mass gain from birth to 12 months in common marmosets (Callithrix jacchus). Lean and fat mass was measured by quantitative magnetic resonance at 1, 2, 6, and 12 months for 31 marmosets, 15 considered Normal and 16 considered Fat (> 14% body fat) at 12 months. Animals were fed either the regular colony diet mix or a high-fat variation. Subjects classified as Fat at 12 months already had greater lean mass (198.4 +/- 6.2 g vs. 174.0 +/- 6.8 g, P = 0.013) and fat mass (45.5 +/- 5.0 g vs. 24.9 +/- 3.4 g, P = .002) by 6 months. Body mass did not differ between groups prior to 6 months, however, by 1 month, Fat infants had greater percent body fat. Percent body fat decreased between 1 and 12 months in Normal subjects; in Fat subjects, it increased. The high-fat diet was associated with body fat > 14% at 6 months (P = 0.049), but not at 12 months. This shift was due to three subjects on the normal diet changing from Normal to Fat between 6 and 12 months. Although maternal prepregnancy adiposity did not differ, overall, between Normal and Fat subjects, the subjects Normal at 6 and Fat at 12 months all had Fat mothers. Therefore, diet and maternal obesity appear to have potentially independent effects that may also vary with developmental age. Although birth weight did not differ between groups, it was associated with fat mass gain from 1 to 6 months in animals with > 14% body fat at 6 months of age (r = 0.612, P = 0.026); but not in 6-month-old animals with < 14% body fat (r = -0.012, P = 0.964). Excess adiposity in captive marmosets develops by 1 month. Birth weight is associated with adiposity in animals vulnerable to obesity.

The endocrine control mechanisms for female mammalian aggression have been largely unstudied. Although it has been proposed that androgens may modulate female aggressive behavior in a similar manner to males, very little conclusive evidence exists. Previous work in male marmosets found that post-encounter increases in testosterone (T) were dependent on the intensity of aggression displayed during the aggressive encounter. We exposed female marmosets (Callithrix kuhlii), a monogamous and biparental primate, to aggressive interactions with unfamiliar intruders. Individual female marmosets exhibited changes in T and estradiol (E(2) ) that are associated with aggressiveness dependent on the intensity of aggression displayed as well as their role during the encounter. Resident females exhibited increased E(2) immediately following an encounter in which they displayed high rates of aggression. If resident females received high rates of aggression from the intruder, the resident displayed increased T 24 hr following the encounter. Interestingly, if the female was an intruder in the encounter, the intensity of her aggression was associated with increased cortisol immediately following the trials, whereas received aggression was associated with increased T and E(2) immediately following the trial. Female primates do exhibit situation-dependent changes in gonadal steroids in association with aggression that may serve to prime them for future aggressive interactions.

The common marmoset (Callithrix jacchus) is poised to become a standard nonhuman primate aging model. With an average lifespan of 5 to 7 years and a maximum lifespan of 16½ years, marmosets are the shortest-lived anthropoid primates. They display age-related changes in pathologies that mirror those seen in humans, such as cancer, amyloidosis, diabetes, and chronic renal disease. They also display predictable age-related differences in lean mass, calf circumference, circulating albumin, hemoglobin, and hematocrit. Features of spontaneous sensory and neurodegenerative change–for example, reduced neurogenesis, ß-amyloid deposition in the cerebral cortex, loss of calbindin D(28k) binding, and evidence of presbycusis–appear between the ages of 7 and 10 years. Variation among colonies in the age at which neurodegenerative change occurs suggests the interesting possibility that marmosets could be specifically managed to produce earlier versus later occurrence of degenerative conditions associated with differing rates of damage accumulation. In addition to the established value of the marmoset as a model of age-related neurodegenerative change, this primate can serve as a model of the integrated effects of aging and obesity on metabolic dysfunction, as it displays evidence of such dysfunction associated with high body weight as early as 6 to 8 years of age.

We offer examples of how proximate and evolutionary forms of argument may inform each other in better understanding reproductive strategy in callitrichid primates, the smallest of the anthropoid primates. In addition, we illustrate how comparative approaches, when applied judiciously, can aid in the formulation of hypotheses regarding even seemingly unique traits within a taxonomic group. In the first example, examination of the nature of genetics in cytokine systems that leads to altered ovulation number in sheep suggests some relatively simple changes could explain both the adaptation of increased ovulation number in marmosets and the subsequent decrease in ovulation number in the closely related species, callimico. In the second example, the role of body size and phylogeny in explaining the role of maternal energy constraints upon gestation and lactation is explored, leading to additional hypotheses regarding these relations in a species that is both small but also in a phylogenetic line selected for slow reproduction. Finally, the role of comparative data in the study of proximate and evolutionary explanations of "unique" human reproductive strategies is discussed.

This report explores aspects of developing obesity in two captive populations of common marmosets (Callithrix jacchus), a small primate with a short lifespan that may be of value in modeling chronic aspects of obesity acquisition and its lifetime effects. Two populations were examined. In study 1, body composition, lipid parameters, and glucose metabolic parameters were measured in a population of 64 adult animals. Animals classified as obese (>80th percentile relative fat based on sex) displayed both dyslipidemia (higher triglyceride and very low-density lipoprotein (VLDL)) and altered glucose metabolism (higher fasting glucose and HbA(1c)). Using operational definitions of atypical values for factors associated with metabolic syndrome in humans, five subjects (7.8%) had at least three atypical factors and five others had two atypical factors. A previously unreported finding in these normally sexually monomorphic primates was higher body weight, fat weights, and percent fat in females compared to males. In a second study, longitudinal weight data for a larger population (n = 210) were analyzed to evaluate the development of high weight animals. Differences in weights for animals that would exceed the 90th percentile in early adulthood were evident from infancy, with a 15% difference in weight between future-large weight vs. their future-normal weight litter mates as early as 4-6 months of age. The marmoset, therefore, demonstrates similar suites of obesity-related alterations to those seen in other primates, including humans, suggesting that this species is worthy of consideration for obesity studies in which its fast maturity, high fertility, relatively short lifespan, and small size may be of advantage.

We describe a cost- and time-efficient method for designing new microsatellite markers in any species with substantial genomic DNA sequence data available. Using this technique, we report 14 new polymorphic dinucleotide microsatellite loci isolated from the common marmoset. The relative yield of new polymorphisms was higher with less labor than described in previous marmoset studies. Of 20 loci initially evaluated, 14 were polymorphic and amplified reliably (70% success rate). The number of alleles ranged from 3 to 9 with heterozygosity varying from 0.48 to 0.83.