Abstract 394: Metabolic Insights into Age and Gender: A New Algorithm for Regional Body Mass Distribution

Abstract

Metabolic syndrome (MetS), a disorder of energy metabolism associated with increased risk of cardiovascular disease (CVD), comprises a cluster of risk factors—low HDL-C, hypertension, hypertriglyceridemia, hyperglycemia and central (abdominal) obesity. Although other investigators noted that non central fat loss, especially femoral gluteal depots, are associated with CVD, the association was not as strong as that with central obesity. We hypothesized that age- and gender-dependent changes in body fat distribution would uncover an underlying cause of MetS. However, it is impossible to compare fat distribution based on anatomical circumferences (C) and skin folds (SF) because of the confounding effects of body mass index (BMI), which rises in the early decades and declines thereafter. We developed an algorithm that adjusts skin folds and circumference data for BMI to obtain a BMI-corrected adiposity index (BAI = C/BMI) for each depot. For comparison over time, we normalized the data set to the value in the third decade of life (BAI 3 = 100) and calculated a normalized BAI. as BAI N = [BAI D /BAI 3 ] X 100. Application of this algorithm to the NHANES I data set of C and SF values, reveals BMI-independent changes in body fat distribution as a function of gender and age, with the most profound changes between the second and eighth decades of life occurring in waist C, which increases with time and buttock C, which decreases over the same time interval. In men the changes begin in the third decade of life. In women, the change does not occur until the beginning of the fifth decade of life, which is approximately the perimenopausal period. We propose a mechanistic model in which the underlying defect in MetS, is impaired fat storage in non-central depots, which results in the transfer of non-esterified fatty acids to skeletal muscle thereby impairing glucose disposal, to liver where it drives VLDL-TG synthesis and secretion, and to central fat depots giving the MetS waistline. The defect is not known but could be tissue-specific apoptosis or insulin resistance. If valid, this model would suggest that therapies that enhanced adipogenesis and/or insulin sensitivity in non-central depots could prevent or delay the onset of MetS.