J. Wagner - Academia.edu (original) (raw)

Papers by J. Wagner

The stable isotopic composition of drinking water, diet, and atmospheric oxygen influence the iso... more The stable isotopic composition of drinking water, diet, and atmospheric oxygen influence the isotopic composition of body water (2H/1H, 18O/16O expressed as δ2H and δ18O). In turn, body water influences the isotopic composition of organic matter in tissues, such as hair and teeth, which are often used to reconstruct historical dietary and movement patterns of animals and humans. Here, we used a nonhuman primate system (Macaca fascicularis) to test the robustness of two different mechanistic stable isotope models: a model to predict the δ2H and δ18O values of body water and a second model to predict the δ2H and δ18O values of hair. In contrast to previous human-based studies, use of nonhuman primates fed controlled diets allowed us to further constrain model parameter values and evaluate model predictions. Both models reliably predicted the δ2H and δ18O values of body water and of hair. Moreover, the isotope data allowed us to better quantify values for two critical variables in the models: the δ2H and δ18O values of gut water and the 18O isotope fractionation associated with a carbonyl oxygen–water interaction in the gut (αow). Our modeling efforts indicated that better predictions for body water and hair isotope values were achieved by making the isotopic composition of gut water approached that of body water. Additionally, the value of αow was 1.0164, in close agreement with the only other previously measured observation (microbial spore cell walls), suggesting robustness of this fractionation factor across different biological systems.

Virology, 2009

Alpha human papillomaviruses (HPVs) are among the most common sexually transmitted agents of whic... more Alpha human papillomaviruses (HPVs) are among the most common sexually transmitted agents of which a subset causes cervical neoplasia and cancer in humans. Alpha-PVs have also been identified in non-human primates although few studies have systematically characterized such mucosal PVs. We cloned and characterized 10 distinct types of PVs from exfoliated cervicovaginal cells from different populations of female cynomolgus macaques (Macaca fascicularis) originating from China and Indonesia. These include 5 novel genotypes and 5 previously identified genotypes found in rhesus (Macaca mulatta) (RhPV-1, RhPV-a, RhPV-b and RhPV-d) and cynomolgus macaques (MfPV-a). Type-specific primers were designed to amplify the complete PV genomes using an overlapping PCR method. Four MfPVs were associated with cervical intraepithelial neoplasia (CIN). The most prevalent virus type was MfPV-3 (formerly RhPV-d), which was identified in 60% of animals with CIN. In addition, the complete genomes of variants of MfPV-3 and RhPV-1 were characterized. These variants are 97.1% and 97.7% similar across the L1 nucleotide sequences with the prototype genomes, respectively. Sequence comparisons and phylogenetic analyses indicate that these novel MfPVs cluster together within the alpha PV α12 species closely related to the α9 (e.g., HPV16) and α11 species (e.g., HPV34), and all share a most recent common ancestor. Our data expand the molecular diversity of nonhuman primate PVs and suggest the recent expansion of alpha PV species groups. Moreover, identification of an overlapping set of MfPVs in rhesus and cynomolgus macaques indicates that non-human primate alpha PVs might not be strictly species specific and that "subtypes" may represent recent divergence of host species or past interspecies infection.

Metabolism, 2008

Isoflavones may influence insulin action by means of their well-known receptor-mediated estrogeni... more Isoflavones may influence insulin action by means of their well-known receptor-mediated estrogenic activity. However, isoflavones also bind to peroxisome proliferator-activated receptors (PPARs) that are strongly associated with insulin action. Soy protein with its isoflavones has previously been shown to improve glycemic control in diabetic postmenopausal women and to improve insulin sensitivity in ovariectomized monkeys. The purpose of the current report was to extend our studies of dietary soy protein to male monkeys and determine effects of the soy isoflavones on insulin resistance. Two studies are reported here. Study one involved 91 male monkeys consuming 3 diets differing only by the source of protein (casein-lactalbumin, soy protein with a low isoflavone concentration, or soy protein with a high isoflavone concentration). Intravenous glucose tolerance tests were done, and plasma adiponectin and lipoprotein concentrations were determined after 25 months of study. Samples of visceral fat were obtained at 31 months for assessment of adiponectin and PPARγ expression. The second study involved 8 monkeys in a Latin-square design that compared the effects of diets with casein/lactalbumin, soy protein with a high isoflavone concentration, or soy protein that was alcohol-washed to deplete the isoflavones. After 8 weeks of treatment, insulin sensitivity and plasma lipoproteins were assessed. At 10 weeks, a biopsy of the skeletal muscle was performed for determination of insulin receptor, PPARα, and PPARγ content. The major findings were that consumption of isoflavone-containing soy protein dose-dependently increased insulin responses to the glucose challenge and decreased plasma adiponectin, whereas isoflavone-depleted soy protein decreased body weight and had no effect on plasma adiponectin concentrations. Muscle PPARα and γ expression was also increased with the isoflavone-depleted soy relative to either casein or soy protein containing the isoflavones. Further studies are needed to determine the mechanisms involved in these effects of a high-soy isoflavone diet and to optimize dietary isoflavone content for maximal health benefits in male subjects.

The Journal of Clinical Endocrinology & Metabolism, 2005

The effects of dietary soy isoflavones (IF) and conjugated equine estrogens (CEE) on circulating ... more The effects of dietary soy isoflavones (IF) and conjugated equine estrogens (CEE) on circulating inflammatory markers were determined at the end of a 3-yr study of ovariectomized monkeys consuming a moderately atherogenic diet. Treatments were: 1) control, receiving alcohol-extracted soyprotein-based diet with low IF content (comparable to ϳ5 mg/d); 2) CEE, added to the control diet at a dose comparable to 0.625 mg/d; and 3) IF, consumed as a part of unextracted soy protein isolate at a dose comparable to 129 mg/d. Serum soluble vascular cell adhesion molecule-1 (sVCAM-1) was reduced by both IF (P < 0.006) and CEE (P < 0.0001) relative to controls. Serum monocyte chemoattractant protein (MCP)-1 was reduced by CEE (P < 0.0001) but not by IF (P ‫؍‬ 1.00). Treatments did not affect serum IL-6 (P ‫؍‬ 0.40), soluble Eselectin (P ‫؍‬ 0.17), or C-reactive protein (P ‫؍‬ 0.15). Serum MCP-1 and, to a lesser extent, IL-6 significantly correlated with atherosclerosis (plaque area) in the iliac and carotid arteries (all P < 0.05). Serum MCP-1 was also strongly associated with coronary artery atherosclerosis and with indices of plaque inflammation and matrix remodeling (matrix metalloproteinase-9) in the coronary artery intima (all P < 0.01).

Type 2 diabetes mellitus is a major health problem of in- creasing incidence. To better study the... more Type 2 diabetes mellitus is a major health problem of in- creasing incidence. To better study the pathogenesis and potential therapeutic agents for this disease, appropriate ani- mal models are needed. Old World nonhuman primates (NHPs) are a useful animal model of type 2 diabetes; like humans, the disease is most common in older, obese ani- mals. Before developing overt

American Journal of Primatology, 2012

The stable isotopic composition of drinking water, diet, and atmospheric oxygen influence the iso... more The stable isotopic composition of drinking water, diet, and atmospheric oxygen influence the isotopic composition of body water ( 2 H/ 1 H, 18 O/ 16 O expressed as δ 2 H and δ 18 O). In turn, body water influences the isotopic composition of organic matter in tissues, such as hair and teeth, which are often used to reconstruct historical dietary and movement patterns of animals and humans. Here, we used a nonhuman primate system (Macaca fascicularis) to test the robustness of two different mechanistic stable isotope models: a model to predict the δ 2 H and δ 18 O values of body water and a second model to predict the δ 2 H and δ 18 O values of hair. In contrast to previous human-based studies, use of nonhuman primates fed controlled diets allowed us to further constrain model parameter values and evaluate model predictions. Both models reliably predicted the δ 2 H and δ 18 O values of body water and of hair. Moreover, the isotope data allowed us to better quantify values for two critical variables in the models: the δ 2 H and δ 18 O values of gut water and the 18 O isotope fractionation associated with a carbonyl oxygen-water interaction in the gut (α ow ). Our modeling efforts indicated that better predictions for body water and hair isotope values were achieved by making the isotopic composition of gut water approached that of body water. Additionally, the value of α ow was 1.0164, in close agreement with the only other previously measured observation (microbial spore cell walls), suggesting robustness of this fractionation factor across different biological systems. Am. J. Primatol. 74:651-660, 2012. C 2012 Wiley Periodicals, Inc.

American Journal of Primatology, 2009

Nutritional interventions are important for reducing obesity and related conditions. Soy is a goo... more Nutritional interventions are important for reducing obesity and related conditions. Soy is a good source of protein and also contains isoflavones that may affect plasma lipids, body weight, and insulin action. Described here are data from a monkey breeding colony in which monkeys were initially fed a standard chow diet that is low fat with protein derived from soy. Monkeys were then randomized to a defined diet with a fat content similar to the typical American diet (TAD) containing either protein derived from soy (TAD soy) or casein-lactalbumin (TAD casein). The colony was followed for over two years to assess body weight, and carbohydrate and lipid measures in adult females (n=19) and their offspring (n=25). Serum isoflavone concentrations were higher with TAD soy than TAD casein, but not as high as when monkey chow was fed. Offspring consuming TAD soy had higher serum isoflavone concentrations than adults consuming TAD soy. Female monkeys consuming TAD soy had better glycemic control, as determined by fructosamine concentrations, but no differences in lipids or body weight compared with those consuming diets with TAD casein. Offspring born to dams consuming TAD soy had similar body weights at birth but over a two-year period weighed significantly less, had significantly lower triglyceride concentrations, and like adult females, had significantly lower fructosamine concentrations compared to TAD casein. Glucose tolerance tests in adult females were not significantly different with diet, but offspring eating TAD soy had increased glucose disappearance with overall lower glucose and insulin responses to the glucose challenge compared with TAD casein. Potential reasons for the additional benefits of TAD soy observed in offspring but not in adults may be related to higher serum isoflavone concentrations in offspring, presence of the diet differences throughout more of their lifespan (including gestation), or different tissue susceptibilities in younger animals.

Obesity, 2007

Characterization and heritability of obesity and associated risk factors in vervet monkeys. Obesi... more Characterization and heritability of obesity and associated risk factors in vervet monkeys. Obesity. 2007;15:1666 -1674. Objective: 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. Design: 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. Subjects: All mature male (n ϭ 98), pregnant (n ϭ 40) and non-pregnant female (n ϭ 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. Measurements: 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. Conclusion: 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.

Virology, 2009

Metabolism, 2008

The Journal of Clinical Endocrinology & Metabolism, 2005

American Journal of Primatology, 2012

The stable isotopic composition of drinking water, diet, and atmospheric oxygen influence the iso... more The stable isotopic composition of drinking water, diet, and atmospheric oxygen influence the isotopic composition of body water ( 2 H/ 1 H, 18 O/ 16 O expressed as δ 2 H and δ 18 O). In turn, body water influences the isotopic composition of organic matter in tissues, such as hair and teeth, which are often used to reconstruct historical dietary and movement patterns of animals and humans. Here, we used a nonhuman primate system (Macaca fascicularis) to test the robustness of two different mechanistic stable isotope models: a model to predict the δ 2 H and δ 18 O values of body water and a second model to predict the δ 2 H and δ 18 O values of hair. In contrast to previous human-based studies, use of nonhuman primates fed controlled diets allowed us to further constrain model parameter values and evaluate model predictions. Both models reliably predicted the δ 2 H and δ 18 O values of body water and of hair. Moreover, the isotope data allowed us to better quantify values for two critical variables in the models: the δ 2 H and δ 18 O values of gut water and the 18 O isotope fractionation associated with a carbonyl oxygen-water interaction in the gut (α ow ). Our modeling efforts indicated that better predictions for body water and hair isotope values were achieved by making the isotopic composition of gut water approached that of body water. Additionally, the value of α ow was 1.0164, in close agreement with the only other previously measured observation (microbial spore cell walls), suggesting robustness of this fractionation factor across different biological systems. Am. J. Primatol. 74:651-660, 2012. C 2012 Wiley Periodicals, Inc.

American Journal of Primatology, 2009

Obesity, 2007