Body mass index is a major determinant of abdominal fat accumulation in pre-, peri- and post-menopausal women.

OBJECTIVE: To investigate the role of menopause, body mass index (BMI) and aging on body fat distribution in women. DESIGN: In this population-based cross-sectional study, 335 women (126 in pre-menopause, 75 in peri-menopause and 134 in post-menopause according to Stages of Reproductive Aging Workshop criteria) were evaluated for body mass composition and fat distribution by dual X-ray absorptiometry procedure. A sub-group of 79 women with similar age and BMI was extracted from the sample to examine the relative influence of BMI in body fat distribution. RESULTS: ANCOVA analysis of total sample showed an age-independent increase of total fat mass (p < 0.001) and percentage on total weight (p < 0.001), arms fat mass (p < 0.01), legs fat mass percentage on total fat (p < 0.05) and trunk fat mass (p < 0.001) and percentage (p < 0.05) in peri- and post- with respect to pre-menopausal women. In the sub-sample including age and BMI matched women the difference of regional fat parameters among menopausal status was no more statistically significant. CONCLUSION: BMI, and not age, is the main determinant of the increase of body fat mass (total and abdominal) observed during the menopausal transition.

Oxidative stress, body fat composition, and endocrine status in pre- and postmenopausal women.

OBJECTIVE: To evaluate the role of menopause on the regional composition and distribution of fat in women and eventual correlations with the oxidative state. DESIGN: In this observational clinical investigation, 90 women (classified for menopause status according to Stages of Reproductive Aging Workshop criteria) were evaluated for body mass composition and fat distribution by dual-energy x-ray absorptiometry and for oxidative status by determination of serum hydroperoxide levels and residual antioxidant activity. RESULTS: Total body fat mass increases significantly in postmenopause (P < 0.05) by 22% in comparison with premenopause, with specific increases in fat deposition at the level of trunk (abdominal and visceral) (P < 0.001) and arms (P < 0.001). Concomitantly, the antioxidant status increases significantly (P < 0.001) by 17%. When data were adjusted for age by analysis of covariance, statistical significance disappeared for the increase in fat mass, but it was retained for antioxidant status (P < 0.05). Both antioxidant status and hydroperoxide level increased with trunk fat mass, as shown by linear correlation analysis (r = 0.46, P < 0.001 and r = 0.26, P < 0.05, respectively). CONCLUSIONS: The results of our investigation demonstrate that fat content increases in the upper part of the body (trunk and arms) in postmenopause and that age is the main determinant of this increase. During the comparison of premenopausal and postmenopausal women, we also detected a significant increase in antioxidant status. Apparently this change is mainly related to menopausal endocrine and fat changes.

Proper orientation of the nicotinamide ring of NADP is important for the precatalytic conformational change in the 6-phosphogluconate dehydrogenase reaction.

A recent study suggested sheep liver 6-phosphogluconate dehydrogenase (6PGDH) sees the oxidized and reduced cofactor differently [Cervellati, C., Dallocchio, F., Bergamini, C. M., and Cook, P. F. (2005) Biochemistry 44, 2432-2440]. Data were consistent with a rotation into the active site of the nicotinamide ring of NADP upon its reduction, resulting in a displacement of the 1-carboxylate of 3-keto-6PG better positioning it for decarboxylation, and further suggested a role of the cofactor in generating the precatalytic conformation of the enzyme. To further probe the role of the cofactor, multiple isotope effects were measured for the enzyme with mutations of the two residues that directly interact with the nicotinamide ring of NADP+, methionine 13 and glutamate 131. Kinetic and isotope effect data obtained in this study will thus be interpreted in terms of a mechanism that includes the rotation of the nicotinamide ring. The M13V, M13Q, M13C, and E131A mutant enzymes were characterized with respect to their kinetic parameters, deuterium, 13C, multiple deuterium/13C isotope effects, and the kinetics of utilization of 2-deoxy-6PG. Data suggest the position of the nicotinamide ring is important in identifying the open and closed conformations of the enzyme, with the latter optimal for catalysis. The 6PGDH reaction provides an excellent example of the use of substrate binding energy to drive catalysis.