Comparison of vitamin D metabolites in wild and captive baboons.

Vitamin D adequacy is essential for multiple physiologic processes. With limited exposure to sunlight for vitamin D3 synthesis, captive primates are supplemented with vitamin D3 (cholecalciferol). Vitamin D metabolite data from wild primates living indigenously could suggest optimum levels. The purpose of this study was to: 1) to explore whether baboons, a speciose genus whose members have significant exposed skin, coat color variation and wide geographical distribution, mirrors the skin pigmentation-vitamin D relationship found in humans; 2) compare vitamin D metabolite levels in wild and captive members of the same or similar baboon species; and 3) apply a recently developed method currently used in humans for measuring multiple vitamin D metabolites as a panel to explore if/how these metabolites can inform us on vitamin D sufficiency. Serum samples from males of three baboon species in the wild: Papio anubis (olive baboon, dark exposed skin), P. cynocephalus (yellow baboon, brown exposed skin), and P. hamadryas (hamadryas baboon, pink exposed skin), were compared with vitamin D supplemented captive olive baboons with sun exposure. Liquid chromatography/tandem mass spectrometry (LC/MS/MS) measured vitamin D and its main metabolites. Cholecalciferol, 25 hydroxyvitamin D2&3 (25(OH)D2&3 ), and 24,25 dihydroxyvitamin D2&3 (24,25(OH)2 D2&3 ), showed significant differences by species. The levels of cholecalciferol due to supplements in the captive olive baboons did not convert to higher 25(OH)D3 while the wild olive baboons exhibited the lowest levels for both cholecalciferol and 25(OH)D3 . Further metabolic conversion of 25(OH)D3 to 24,25(OH)2 D3 indicated that all baboons had more similar conversion ratios and these were within the same range found for humans that are depicted as having adequate vitamin D levels. This study provided evidence that exposed skin color does influence vitamin D3 levels, with lower levels in darker skinned species, but these differences are eliminated in the downstream metabolite conversion indicating strong regulatory control.

Diet-induced early-stage atherosclerosis in baboons: Lipoproteins, atherogenesis, and arterial compliance.

BACKGROUND: The purpose of this study was to determine whether dietary manipulation can reliably induce early-stage atherosclerosis and clinically relevant changes in vascular function in an established, well-characterized non-human primate model. METHODS: We fed 112 baboons a high-cholesterol, high-fat challenge diet for two years. We assayed circulating biomarkers of cardiovascular disease (CVD) risk, at 0, 7, and 104 weeks into the challenge; assessed arterial compliance noninvasively at 104 weeks; and measured atherosclerotic lesions in three major arteries at necropsy. RESULTS: We observed evidence of atherosclerosis in all but one baboon fed the two-year challenge diet. CVD risk biomarkers, the prevalence, size, and complexity of arterial lesions, plus consequent arterial stiffness, were increased in comparison with dietary control animals. CONCLUSIONS: Feeding baboons a high-cholesterol, high-fat diet for two years reliably induces atherosclerosis, with risk factor profiles, arterial lesions, and changes in vascular function also seen in humans.

Renal histopathology of a baboon model with type 2 diabetes.

Naturally occurring type 2 diabetes has been found in a colony of baboons. Ongoing characterization of the baboon colony maintained at the Southwest National Primate Research Center has revealed a significant range of glucose sensitivity with some animals clearly diabetic.   Seven baboons, four with diabetes and three without diabetes, underwent histopathological investigation. Three diabetic animals were diagnosed using fasting blood glucose, hemoglobin A1C, and intravenous glucose tolerance test, and a fourth one was known to have hyperglycemia. One control baboon and three baboons with diabetes had microalbuminuria. On kidney biopsy, diabetic baboons had thickening of the glomerular basement membrane and mesangial matrix expansion compared to controls. Immunohistochemistry showed the diabetic animals had increased mesangial expression of cellular fibronectin ED-A. Two diabetic animals with microalbuminuria had evidence of mesangiolysis with the formation of an early nodule. One diabetic animal had a Kimmestiel-Wilson nodule. We conclude that the baboon represents a useful primate model of diabetes and nephropathy that resembles the nephropathy associated with type 2 diabetes in humans.

Telomere shortening in leukocyte subpopulations from baboons.

To address questions about telomere length regulation in nonhuman primates, we studied the telomere length in subpopulations of leukocytes from the peripheral blood of baboons aged 0.2-26.5 years. Telomere length in granulocytes, B cells, and subpopulations of T cells all decreased with age. Overall, telomere length kinetics were lineage- and cell subset-specific. T cells showed the most pronounced, overall decline in telomere length. Levels of telomerase in stimulated T cells from old animals were lower than in corresponding cells from young animals. Memory T cells with very short telomeres accumulated in old animals. In contrast, the average telomere length values in B cells remained relatively constant from middle age onward. Individual B cells showed highly variable telomere length, and B cells with very long telomeres were observed after the ages of 1-2 years. In general, cell type-specific telomere kinetics in baboons were remarkably similar to those observed in humans.