SUSTAINED WEIGHT-REDUCTION IN MODERATELY OBESE WOMEN RESULTS IN DECREASED ACTIVITY OF SKELETAL-MUSCLE LIPOPROTEIN-LIPASE

Obesity is an increasingly prevalent problem, and long-term maintenance of the weight-reduced state is difficult for the obese individual. Following weight reduction, many metabolic changes occur. Among these is an increase in adipose tissue lipoprotein lipase (ATLPL), which predicts an alteration in lipid fuel partitioning which may then contribute to resumption of the obese state. The purpose of this study was to test whether changes in skeletal muscle LPL (SMLPL) and its response to insulin/glucose after sustained weight reduction also indicate a potential altered partitioning of lipid fuels away from oxidative pathways in muscle to storage in adipose tissue. Biopsies of vastus lateralis muscle were carried out in premenopausal obese women (n=11, 94+/-4 kg, mean+/-SEM) before and after consumption of a 900 kcal day(-1) diet for 3 months followed by 3 months of isocaloric maintenance of the reduced weight (n=11, 82+/-4 kg). SMLPL activity was measured in the fasted state and after 6 h insulin/glucose infusion, before and after sustained weight loss. SMLPL activities were also measured in six normal weight women. Fasting SMLPL activity in obese women (39+/-0.3 nmol FFA min(-1) g(-1)) was similar to that measured in normal weight control women (4.4+/-0.5). Unlike normal weight controls in whom a 6 h insulin/glucose infusion decreased SMLPL activity, in obese women the response of SMLPL was positive (normal weight vs, obese: Delta-0.8+/-0.3 vs. Delta 1.6+/-0.5, P=0.002). Following maintained weight reduction, fasting SMLPL in the obese group was reduced to 1.2+/-0.3 (obese before weight loss vs. obese after: P=0.0001). This change in fasting SMLPL activity following weight loss/maintenance correlated with the resultant change in per cent body fat (r(s)=0.663, P=0.026). Following sustained weight reduction in the obese women, the change in SMLPL activity in response to insulin/glucose infusion was unchanged by statistical comparison. However, the trend of the direction of that change was toward a more normal value. Overall, the decrease in SMLPL which occurred following sustained weight loss may explain, in part, why prolonged weight reduction in obese subjects is difficult to maintain.