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1.  Body composition and cardiometabolic disease risk factors in captive baboons (Papio hamadryas Sp.): sexual dimorphism 
Baboons (Papio hamadryas Sp.) exhibit significant sexual dimorphism in body size. Sexual dimorphism is also exhibited in a number of circulating factors associated with risk of cardiometabolic disease. We investigated whether sexual dimorphism in body size and composition underlie these differences. We examined data from 28 male and 24 female outdoor group-housed young adult baboons enrolled in a longitudinal observational study of cardiometabolic disease risk factors. Animals were sedated with ketamine HCl (10mg/Kg) before undergoing venous blood draws, basic body measurements, and dual-energy X-ray absorptiometry (DXA) body composition scans. Percentage glycated hemoglobin (%HbA1C) was measured in whole blood. Serum samples were analyzed for glucose, insulin, C-peptide, HDL-, and triglyceride concentrations. Males were heavier and had greater body length and lean tissue mass than females. Females had a greater body fat percentage relative to males (10.8 ±6.4 vs. 6.9 ±4.0, P=0.01). Although C-peptide, fasting glucose, and %HbA1C did not differ between the sexes, females had greater fasting insulin and triglyceride compared to their male counterparts. Insulin and percentage body fat were significantly correlated in males (r=0.61, P=0.001) and to a lesser extent in females (r=0.43, P=0.04). Overall, relations between adiposity and fasting insulin and fasting triglyceride were stronger in males. After accounting for differences in percentage body fat, fasting insulin and triglyceride were no longer statistically different between males and females. Despite stronger correlations between relative adiposity and insulin and triglyceride in males, the higher fasting insulin and triglyceride of female baboons may be underlain by their greater relative body fat masses.
PMCID: PMC4025923  PMID: 24318937
sex differences; baboon; body fat; triglyceride; insulin
2.  Hyperglycemic Challenge and Distribution of Adipose Tissue in Obese Baboons 
Blood glucose levels regulate the rate of insulin secretion, which is the body’s mechanism for preventing excessive elevation in blood glucose. Impaired glucose metabolism and insulin resistance have been linked to excess body fat composition. Here, we quantify abdominal muscle and abdominal adipose tissue compartments in a large nonhuman primate, the baboon, and investigate their relationship with serum glucose response to a hyperglycemic challenge.
Five female baboons were fasted for 16 hours prior to 90 minute body imaging experiment that consisted of a 20-min baseline, followed by a bolus infusion of glucose (500mg/kg). The blood glucose was sampled at regular intervals. The total volumes of the muscle, visceral and subcutaneous adipose tissue were measured.
Results and discussion
We found that adipose tissue composition predicted fluctuations in glucose responses to a hyperglycemic challenge of a non-human primate. Animals with higher visceral adiposity showed significantly reduced glucose elimination. The glucose responses were positively correlated with body weight, visceral and muscle fat (p < 0.005). Polynomial regression analysis showed that body weight, visceral and muscle were significant
These results reveal the similarity between humans and baboons with respect to glucose metabolism and strengthen the utility of baboon for biomedical research.
PMCID: PMC4241571  PMID: 25429366
Hyperglycemic Challenge; Perfusion Imaging; Body Fat Composition
3.  Entero-insular axis and postprandial insulin differences in African American and European American children 
African Americans (AA) have a greater post-glucose-challenge insulin response than European Americans (EA). Factors underlying this response are unknown.
To determine the insulin, C-peptide, and incretin responses to a mixed macronutrient meal in AA and EA children. We hypothesized that: 1) AA would have greater postprandial insulin and C-peptide responses; 2) AA would have higher incretin responses; 3) the greater β-cell response among AA would be explained by greater incretin responses.
Subjects were 34 AA and 18 EA children. Glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) were measured after consumption of a liquid mixed meal. Insulin, C-peptide, and incretin responses were derived from the area-under-the curve (AUC) for minutes 0-30 (“early response”) and minutes 30-180 (“late response”) following meal ingestion
The early insulin response was higher in AA (14,565 ±6,840 pmol/L × 30min) vs. EA (7,450 ±4,077 pmol/L × 30min, P<0.001). Early C-peptide AUC did not differ by ethnicity (34.8 ±12.5 vs. 28.6 ±12.5nmol/L ×30mins, for AA and EA, respectively; P=0.10). Early and late GLP-1 responses were lower in AA vs EA (108.1 ±56.4 vs. 160.5 ±90.8pmol/L ×30mins) and (509.4 ±286.9 vs. 781.9 ±483.4pmol/L ×150mins), respectively (P<0.05 for both). The GIP response did not differ between groups.
Greater early insulin response in AA vs. EA is not due to differences in circulating GLP-1 or GIP, and may be due to lesser insulin clearance. Further research is needed to determine the physiologic implications of lower GLP-1 among AA.
PMCID: PMC2785031  PMID: 18996863
4.  A preliminary report on the feeding of cynomolgus monkeys (Macaca fascicularis) with a high sugar high fat diet for 33 weeks 
Journal of Medical Primatology  2011;40(5):335-341.
The metabolic syndrome is common in populations exposed to a typical Western diet. There is a lack of an animal model that mimics this condition.
We fed 15 cynomolgus monkeys ad libitum a high sugar high fat (HSHF) diet for 33 weeks. Body weight, body composition, serum lipids and insulin were measured at baseline and at 33 weeks.
The animals tolerated the HSHF diet very well. In the intervention group, total serum cholesterol and LDL-C were 3- and 5-fold higher, respectively, at 33 weeks as compared to their baseline levels. Serum HDL-C and triglycerides were not significantly affected. Dual-energy X-ray absorptiometry (DXA) analysis of the intervention group indicated that the trunk fat mass increased by 187% during this period.
Cynomolgus monkeys should be a useful model for investigating the interactions of diet and other factors such as genetics in the development of the metabolic syndrome.
PMCID: PMC3282177  PMID: 21812784
Dual X-ray absorptiometry; LDL-cholesterol; triglyceride; insulin
5.  Variants in CPT1A, FADS1, and FADS2 are Associated with Higher Levels of Estimated Plasma and Erythrocyte Delta-5 Desaturases in Alaskan Eskimos 
The delta-5 and delta-6 desaturases (D5D and D6D), encoded by fatty acid desaturase 1 (FADS1) and 2 (FADS2) genes, respectively, are rate-limiting enzymes in the metabolism of ω-3 and ω-6 fatty acids. The objective of this study was to identify genes influencing variation in estimated D5D and D6D activities in plasma and erythrocytes in Alaskan Eskimos (n = 761) participating in the genetics of coronary artery disease in Alaska Natives (GOCADAN) study. Desaturase activity was estimated by product: precursor ratio of polyunsaturated fatty acids. We found evidence of linkage for estimated erythrocyte D5D (eD5D) on chromosome 11q12-q13 (logarithm of odds score = 3.5). The confidence interval contains candidate genes FADS1, FADS2, 7-dehydrocholesterol reductase (DHCR7), and carnitine palmitoyl transferase 1A, liver (CPT1A). Measured genotype analysis found association between CPT1A, FADS1, and FADS2 single-nucleotide polymorphisms (SNPs) and estimated eD5D activity (p-values between 10−28 and 10−5). A Bayesian quantitative trait nucleotide analysis showed that rs3019594 in CPT1A, rs174541 in FADS1, and rs174568 in FADS2 had posterior probabilities > 0.8, thereby demonstrating significant statistical support for a functional effect on eD5D activity. Highly significant associations of FADS1, FADS2, and CPT1A transcripts with their respective SNPs (p-values between 10−75 and 10−7) in Mexican Americans of the San Antonio Family Heart Study corroborated our results. These findings strongly suggest a functional role for FADS1, FADS2, and CPT1A SNPs in the variation in eD5D activity.
PMCID: PMC3371589  PMID: 22701466
essential fatty acids; single-nucleotide polymorphisms; bayesian quantitative trait nucleotide analysis
6.  Coordinated Defects in Hepatic Long Chain Fatty Acid Metabolism and Triglyceride Accumulation Contribute to Insulin Resistance in Non-Human Primates 
PLoS ONE  2011;6(11):e27617.
Non-Alcoholic fatty liver disease (NAFLD) is characterized by accumulation of triglycerides (TG) in hepatocytes, which may also trigger cirrhosis. The mechanisms of NAFLD are not fully understood, but insulin resistance has been proposed as a key determinant.
To determine the TG content and long chain fatty acyl CoA composition profile in liver from obese non-diabetic insulin resistant (IR) and lean insulin sensitive (IS) baboons in relation with hepatic and peripheral insulin sensitivity.
Twenty baboons with varying grades of adiposity were studied. Hepatic (liver) and peripheral (mainly muscle) insulin sensitivity was measured with a euglycemic clamp and QUICKI. Liver biopsies were performed at baseline for TG content and LCFA profile by mass spectrometry, and histological analysis. Findings were correlated with clinical and biochemical markers of adiposity and insulin resistance.
Obese IR baboons had elevated liver TG content compared to IS. Furthermore, the concentration of unsaturated (LC-UFA) was greater than saturated (LC-SFA) fatty acyl CoA in the liver. Interestingly, LC-FA UFA and SFA correlated with waist, BMI, insulin, NEFA, TG, QUICKI, but not M/I. Histological findings of NAFLD ranging from focal to diffuse hepatic steatosis were found in obese IR baboons.
Liver TG content is closely related with both hepatic and peripheral IR, whereas liver LC-UFA and LC-SFA are closely related only with hepatic IR in non-human primates. Mechanisms leading to the accumulation of TG, LC-UFA and an altered UFA: LC-SFA ratio may play an important role in the pathophysiology of fatty liver disease in humans.
PMCID: PMC3220682  PMID: 22125617
7.  Feto-placental adaptations to maternal obesity in the baboon 
Placenta  2009;30(9):752-760.
Maternal obesity is present in 20–34% of pregnant women and has been associated with both intrauterine growth restriction and large-for-gestational age fetuses. While fetal and placental functions have been extensively studied in the baboon, no data are available on the effect of maternal obesity on placental structure and function in this species. We hypothesize that maternal obesity in the baboon is associated with a maternal inflammatory state and induces structural and functional changes in the placenta. The major findings of this study were 1) decreased placental syncytiotrophoblast amplification factor, intact syncytiotrophoblast endoplasmic reticulum structure and decreased system A placental amino acid transport in obese animals; 2) fetal serum amino acid composition and mononuclear cells (PBMC) transcriptome were different in fetuses from obese compared with non-obese animals 3) maternal obesity in humans and baboons is similar in regard of increased placental and adipose tissue macrophage infiltration, increased CD14 expression in maternal PBMC and maternal hyperleptinemia. In summary, these data demonstrate that in obese baboons in the absence of increased fetal weight, placental and fetal phenotype are consistent with those described for large- for-gestational age human fetuses.
PMCID: PMC3011231  PMID: 19632719
8.  Eight week exposure to a high sugar high fat diet results in adiposity gain and alterations in metabolic biomarkers in baboons (Papio hamadryas sp.) 
Baboons (Papio hamadryas Sp.) develop features of the cardiometabolic syndrome and represent a clinically-relevant animal model in which to study the aetiology of the disorder. To further evaluate the baboon as a model for the study of the cardiometabolic syndrome, we developed a high sugar high fat diet and hypothesized that it could be used to induce adiposity gain and affect associated circulating biomarkers.
We developed a diet enriched with monosaccharides and saturated fatty acids that was composed of solid and liquid energy sources. We provided a group of baboons (n = 9) ad libitum access to this diet for 8 weeks. Concurrently, a control group (n = 6) was maintained with ad libitum access to a low sugar low fat baseline diet and normal water for 8 weeks. Body composition was determined by dual-energy X-ray absorptiometry and circulating metabolic biomarkers were measured using standard methodology before and after the 8 week study period.
Neither body composition nor circulating biomarkers changed in the control group. Following the 8 weeks, the intervention group had a significant increase in fat mass (1.71 ± 0.98 vs. 3.23 ± 1.70 kg, p = 0.004), triglyceride (55 ± 13 vs. 109 ± 67 mg/dL, p = 0.006,), and leptin (1.19 ± 1.40 vs. 3.29 ± 2.32 ng/mL, p = 0.001) and a decline in adiponectin concentrations (33530 ± 9744 vs. 23330 ± 7863 ng/mL, p = 0.002). Percentage haemoglobin A1C (4.0 ± 0.3 vs. 6.0 ± 1.4, p = 0.002) also increased in the intervention group.
Our findings indicate that when exposed to a high sugar high fat diet, young adult male baboons develop increased body fat and triglyceride concentrations, altered adipokine concentrations, and evidence of altered glucose metabolism. Our findings are in keeping with observations in humans and further demonstrate the potential utility of this highly clinically-relevant animal model for studying diet-induced metabolic dysregulation.
PMCID: PMC2988722  PMID: 21034486
9.  Validity of new child-specific thoracic gas volume prediction equations for air-displacement plethysmography 
BMC Pediatrics  2006;6:18.
To determine the validity of the recently developed child-specific thoracic gas volume (TGV) prediction equations for use in air-displacement plethysmography (ADP) in diverse pediatric populations.
Three distinct populations were studied: European American and African American children living in Birmingham, Alabama and European children living in Lisbon, Portugal. Each child completed a standard ADP testing protocol, including a measured TGV according to the manufactures software criteria. Measured TGV was compared to the predicted TGV from current adult-based ADP proprietary equations and to the recently developed child-specific TGV equations of Fields et al. Similarly, percent body fat, derived using the TGV prediction equations, was compared to percent body fat derived using measured TGV.
Predicted TGV from adult-based equations was significantly different from measured TGV in girls from each of the three ethnic groups (P < 0.05), however child-specific TGV estimates did not significantly differ from measured TGV in any of the ethnic or gender groups. Percent body fat estimates using adult-derived and child-specific TGV estimates did not differ significantly from percent body fat measures using measured TGV in any of the groups.
The child-specific TGV equations developed by Fields et al. provided a modest improvement over the adult-based TGV equations in an ethnically diverse group of children.
PMCID: PMC1526421  PMID: 16753062
10.  Assessment of body composition by air-displacement plethysmography: influence of body temperature and moisture 
To investigate the effect of body temperature and moisture on body fat (%fat), volume and density by air-displacement plethysmography (BOD POD).
%fat, body volume and density by the BOD POD before (BOD PODBH) and immediately following hydrostatic weighing (BOD PODFH) were performed in 32 healthy females (age (yr) 33 ± 11, weight (kg) 64 ± 14, height (cm) 167 ± 7). Body temperature and moisture were measured prior to BOD PODBH and prior to BOD PODFH with body moisture defined as the difference in body weight (kg) between the BOD PODBH and BOD PODFH measurements.
BOD PODFH %fat (27.1%) and body volume (61.5 L) were significantly lower (P ≤ 0.001) and body density (1.0379 g/cm3) significantly higher (P ≤ 0.001) than BOD PODBH %fat (28.9%), body volume (61.7 L), and body density (1.0341 g/cm3). A significant increase in body temperature (~0.6°C; P ≤ 0.001) and body moisture (0.08 kg; P ≤ 0.01) were observed between BOD PODBH and BOD PODFH. Body surface area was positively associated with the difference in %fat independent of changes in body temperature and moisture, r = 0.30, P < 0.05.
These data demonstrate for the first time that increases in body heat and moisture result in an underestimation of body fat when using the BOD POD, however, the precise mechanism remains unidentified.
PMCID: PMC411054  PMID: 15059287
Body volume; body fat; Body surface area; BOD POD; Air-displacement plethysmography

Results 1-10 (10)