As part of our efforts to further expand the utility of our baboon resource we are actively pursuing a metabolic profiling initiative to track changes in a variety of important physiological and metabolic parameters in a cohort of animals throughout their adult life. We have now completed the data collection for the first three years of profiling in our initial cohort of animals. The age of the animals at baseline were between 7 to 8 years of age corresponding physiologically to early adulthood in humans. With regards to measures of body composition, there already appear to be both cohort and individual trends beginning to emerge. During this time period the percent body fat of females has increased while that of the males has remained relatively stable. This difference between the sexes is also not completely unexpected as the females tend to mature at an earlier age than the males, however, we anticipate that the males will begin exhibiting a similar trend to what has been seen in the females as they move into the next phase of the study.
However, when we look at individual trends in both changes in body weight and percent body fat in both females and males several individuals are beginning to exhibit significant gains compared to the other animals in the cohort. As can be seen in both figures in regards to body weight most animals showed a general trend of increasing weight over time, however, this increase in most cases appears to correspond to general growth of the animals overall, but a few of these animals appear to be gaining a disproportionate amount of weight over this time period as compared to the rest of the cohort. In comparison, the figures showing the change in percent body fat in both sexes reveal that some animals maintain a fairly constant percentage of body fat even in the presence of some weight gain but a few animals are beginning to show a substantial increase in percent body fat. We anticipate that this trend in fat accumulation will continue as these animals continue to age. We would predict that the animals which are now beginning to exhibit the greatest increases in percent body fat are the most likely candidates for the development of metabolic diseases such as CVD and T2D, again based on our prior retrospective observations. As a result the data we have now begun to accumulate can help in more effectively selecting the most appropriate animals for experimental work focused on these conditions.
Assessment of Insulin sensitivity in baboons
In our ongoing effort to establish the baboon as a model for the study of Type 2 Diabetes (T2D) we have recently completed a series of hyperinsulinemic euglycemic clamp procedures in a cohort of adult baboons of varying body weights (Chavez et al. Diabetes. 2008 Apr;57(4):899-908). The hyperinsulinemic euglycemic clamp procedure is considered a “gold standard’ for the assessment of insulin sensitivity. Based upon the results obtained from the clamp procedure the baboons could be divided into insulin sensitive and insulin resistant animals based upon an Rd value > 6.0 or < 4.0 mg/kg•min (the Rd value is a measure of insulin mediated glucose disposal in muscle). Thus, at the whole body and molecular levels, the insulin resistance in baboons closely resembles the development of insulin resistance in obese humans. In both males and females the severity of whole body insulin resistance is similarly related to the increase in abdominal adiposity. Since waist circumference correlated highly with both % body fat and body mass index, the use of anthropometric measurements provides a simple surrogate marker to screen animals that are more likely to manifest the insulin resistant phenotype. These findings support the use of the baboon as a pertinent nonhuman primate model for the study of the underlying cellular/molecular mechanisms responsible for insulin resistance and development of T2DM, as well as to examine pharmacologic interventions to reverse insulin resistance and treat T2D in humans.