Article

Characterization and Heritability of Obesity and Associated Risk Factors in Vervet Monkeys*

Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA.
Obesity (Impact Factor: 4.39). 08/2007; 15(7):1666-74. DOI: 10.1038/oby.2007.199
Source: PubMed

ABSTRACT The objective was to determine the prevalence and heritability of obesity and risk factors associated with metabolic syndrome (MS) in a pedigreed colony of vervet monkeys.
A cross-sectional study of plasma lipid and lipoprotein concentrations, glycemic indices, and morphometric measures with heritability calculated from pedigree analysis. A selected population of females was additionally assessed for insulin sensitivity and glucose tolerance.
All mature male (n=98), pregnant (n=40) and non-pregnant female (n=157) vervet monkeys were included in the study. Seven non-pregnant females were selected on the basis of high or average glycated hemoglobin (GHb) for further characterization of carbohydrate metabolism.
Morphometric measurements included body weight, length, waist circumference, and calculated BMI. Plasma lipids [total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C)] and glycemic measures (fasting blood glucose, insulin, and GHb) were measured. A homeostasis model assessment index was further reported. Glucose tolerance testing and hyperinsulinemic-euglycemic clamps were performed on 7 selected females.
Vervet monkeys demonstrate obesity, insulin resistance, and associated changes in plasma lipids even while consuming a low-fat (chow) diet. Furthermore, these parameters are heritable. Females are at particular risk for central obesity and an unfavorable lipid profile (higher TG, TC, and no estrogen-related increase in HDL-C). Selection of females by elevated GHb indicated impaired glucose tolerance and was associated with central obesity. This colony provides a unique opportunity to study the development of obesity-related disorders, including both genetic and environmental influences, across all life stages.

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    • "Under this dietary condition, these cardiometabolic traits are significantly heritable, with the estimates ranging between 20% and 45% [Kavanagh et al., 2007a]. However , these monkeys have also been characterized as good models for studying genetics of cardiometabolic disorders through dietary manipulations [Kavanagh et al., 2007a; Rudel et al., 1995]. When fed diets with 35% of energy derived from trans-monounsaturated fatty acids, as compared to cis-monounsaturated fatty acids, vervets gained significant weight and abdominal fat in spite of controlled food intake (Kavanagh et al., 2007b). "
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    ABSTRACT: Nutrient composition of a diet (D) has been shown to interact with genetic predispositions (G) to affect various lipid phenotypes. Our aim in this study was to confirm G × D interaction and determine whether the interaction extends to other cardiometabolic risk factors such as glycemic measures and body weight. Subjects were vervet monkeys (Chlorocebus aethiops sabaeus; n = 309) from a multigenerational pedigreed colony initially fed with a plant-based diet, standard primate diet (18% calories from protein, 13% from fat, and 69% from carbohydrates), and subsequently challenged for 8 weeks with a diet modeled on the typical American diet (18% calories from protein, 35% from fat, and 47% from carbohydrates). Our results showed that although exposure to the challenge diet did not result in significant changes in weight, most lipid and glycemic biomarkers moved in an adverse direction (P < 0.01). Quantitative genetic analyses showed that cardiometabolic phenotypes were significantly heritable under both dietary conditions (P < 0.05), and there was significant evidence of G × D interaction for these phenotypes. We observed significant differences in the additive genetic variances for most lipid phenotypes (P < 10(-4) ), indicating that the magnitude of genetic effects varies by diet. Furthermore, genetic correlations between diets differed significantly from 1 with respect to insulin, body weight, and some lipid phenotypes (P < 0.01). This implied that distinct genetic effects are involved in the regulation of these phenotypes under the two dietary conditions. These G × D effects confirm and extend previous observations in baboons (Papio sp.) and suggest that mimicking the typical human nutritional environment can reveal genetic influences that might not be observed in animals consuming standard, plant-based diets. Am. J. Primatol. 00:1-9, 2013. © 2013 Wiley Periodicals, Inc.
    American Journal of Primatology 05/2013; 75(5). DOI:10.1002/ajp.22125 · 2.14 Impact Factor
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    • "Vervets offer several advantages to other OWMs: they are a nonendangered species that adapt well to captive environments, and in contrast to other nonhuman primates, Caribbean origin vervets are typically free of herpes virus B, immunodeficiency viruses, and retrovirus, and do not harbor any of the known African pathogenic viruses (Jasinska et al., 2012). These properties make them appealing to carry out basic and translational research, and in particular have proven to be valuable for studies of metabolic disorders including type 2 diabetes (Kavanagh et al., 2007). Vervets have been used for cognitive studies relevant to human diseases including schizophrenia (Freimer et al., 2007), aging (Melega et al., 2008), and attention deficit disorder (Seu et al., 2009); and have been used for stem cell transplantation studies addressing Parkinson's disease (Taylor et al., 1997). "
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    ABSTRACT: The vervet is an old world monkey increasingly being used as a model for human diseases. In addition to plaques and tangles, an additional hallmark of Alzheimer's disease is damage to neurons that synthesize noradrenaline (NA). We characterized amyloid burden in the posterior temporal lobe of young and aged vervets, and compared that with changes in NA levels and astrocyte activation. Total amyloid beta (Aβ)40 and Aβ42 levels were increased in the aged group, as were numbers of amyloid plaques detected using antibody 6E10. Low levels of Aβ42 were detected in 1 of 5 younger animals, although diffusely stained plaques were observed in 4 of these. Increased glial fibrillary acidic protein staining and messenger RNA levels were significantly correlated with increased age, as were cortical NA levels. Levels of Aβ42 and Aβ40, and the number of 6E10-positive plaques, were correlated with NA levels. Interestingly messenger RNA levels of glial derived neurotrophic factor, important for noradrenergic neuronal survival, were reduced with age. These findings suggest that amyloid pathology in aged vervets is associated with astrocyte activation and higher NA levels.
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    • "Captive adult nonhuman primates also display obesity. Species in which spontaneous or diet-induced obesity in a captive setting have been described include macaques (Kemnitz, 1984; Bodkin et al., 1993; Wagner et al., 2006), vervet monkeys (Kavanagh et al., 2007), baboons (Comuzzie et al., 2003), squirrel monkeys (Ausman et al., 1981) and marmosets (Tardif et al., 2009; Wachtman et al., 2011). Weight gain associated with infection of adult macaques and marmosets with human adenovirus AD36 has been reported (Dhurandhar et al., 2002). "
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