Faculty Bibliography

There is renewed interest in Siri's classic three-compartment (3C) body composition model, requiring body volume (BV) and total body water (TBW) estimates, because dual-energy X-ray absorptiometry (DEXA) and in vivo neutron activation (IVNA) systems cannot accommodate subjects with severe obesity. However, the 3C model assumption of a constant ratio (alpha) of mineral (M) to total body protein (TBPro) and related residual mass density (D(RES)) based on cadaver analyses might not be valid across groups differing in sex, race, age, and weight. The aim of this study was to derive new 3C model coefficients in vivo and to compare these estimates to those derived by Siri. Healthy adults (n = 323) were evaluated with IVNA and DEXA and the measured components used to derive alpha and D(RES). For all subjects combined, values of alpha and D(RES) (means +/- SD, 0.351 +/- 0.043; 1.565 +/- 0.023 kg/l) were similar to Siri's proposed values of 0.35 and 1.565 kg/l, respectively. However, alpha and D(RES) varied significantly as a function of sex, race, weight, and age. Expected errors in percent body fat arising by application of Siri's model were illustrated in a second group of 264 adults, including some whose size exceeded DEXA limits but whose BV and TBW had been measured by hydrodensitometry and (2)H(2)O dilution, respectively. Extrapolation of predictions by newly developed models to very high weights allows percent fat error estimation when Siri's model is applied in morbidly obese subjects. The present study results provide a critical evaluation of potential errors in the classic 3C model and present new formulas for use in selected populations.

The association of melanocortin peptide overproduction with enhanced linear growth prompted the current investigation of adrenocorticotropin hormone (ACTH) effects on multipotential chondroprogenitor populations and committed chondrocytes in culture. Two multipotential progenitor populations, rat bone marrow stromal cells (BMSC) and the clonal multipotential cell line RCJ3.1, and two committed chondrocyte populations, resting chondrocytes (RC) isolated from the rib of young rats and the chondrocyte restricted cell line RCJ3.1C5.18 (C5.18), were cultured in differentiation medium plus or minus ACTH. Alcian blue stain was used to quantitate proteoglycan matrix production in all populations treated with a range of ACTH concentrations. Changes in proliferation due to ACTH treatment of all cell types were measured using 3H-thymidine incorporation. Differences in matrix production of ACTH-treated and -untreated RC and C5.18 cells were determined using 3H-proline incorporation. Relative transcript expression of the chondrocyte matrix proteins collagen type II (COLL II) and aggrecan (AGR) in treated and untreated cells was analyzed by Northern blot. Collagen type X (COLL X), a marker of hypertrophic differentiation, was measured in committed chondrocytic populations. Western analysis was used to detect the melanocortin-3 receptor (MC3-R), which was a suspected mediator of the ACTH signal. Matrix deposition was dose-dependently increased by ACTH in all cell populations as measured by alcian blue stain. ACTH treatment increased proliferation in multipotential progenitor populations (BMSC and RCJ3.1) while proliferation was decreased in committed chondrocyte populations (RC and C5.18). Total protein and total cell-associated collagen production were significantly increased by ACTH treatment in committed populations. Relative COLL II and AGR transcript expressions were significantly increased in both the RC- and C5.18-committed population and very significantly increased in the progenitor populations. Additionally, collagen type X expression was detected earlier and in greater abundance in ACTH-treated committed chondrocyte populations. Finally, the melanocortin-3 receptor was detected in all examined cell types by Western blot. These data show that ACTH promotes the development of the chondrocyte phenotype from multipotential mesenchymal progenitor populations and increases matrix production and differentiation of committed chondrocytes. These findings, together with the detection of the MC3-R in all of these cell types, indicate a role for the melanocortin system in chondrogenesis.

BACKGROUND: Protein is an important body component, and the presently accepted criterion method for estimating total body protein (TBPro) mass--in vivo neutron activation (IVNA) analysis--is unavailable to most investigators and is associated with moderate radiation exposure. OBJECTIVE: The objective was to derive a theoretical cellular level TBPro mass and distribution model formulated on measured total body potassium, total body water, and bone mineral and to evaluate the new model with the IVNA method as the criterion. DESIGN: The new model was developed on the basis of a combination of theoretical equations and empirically derived coefficients. TBPro mass estimates with the new model were evaluated in healthy women (n = 183) and men (n = 24) and in men with AIDS (n = 84). Total body nitrogen was measured by IVNA, total body potassium by whole-body (40)K counting, total body water by tritium dilution, and bone mineral by dual-energy X-ray absorptiometry. RESULTS: The group mean (+/- SD) TBPro mass estimates in healthy women and men and men with AIDS (8.2 +/- 0.9, 11.0 +/- 1.8, and 10.5 +/- 1.1 kg, respectively) with the new model were similar to IVNA criterion estimates (8.9 +/- 0.9, 11.1 +/- 1.6, and 10.9 +/- 1.2 kg, respectively). TBPro mass estimates with the new model correlated highly with the IVNA estimates in all subjects combined (r = 0.92, P < 0.001). The new model suggests that the composite TBPro mass within each group consists mainly of cellular protein (75-79%) and, to a lesser extent, protein in extracellular solids (19-23%) and extracellular fluid (approximately 2%). CONCLUSION: The new model provides a non-IVNA approach for estimating protein mass and distribution in vivo.