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 maintenanc e of the weight-reduced state is difficult for the obese individual. F ollowing weight reduction, many metabolic changes occur. Among these i s an increase in adipose tissue lipoprotein lipase (ATLPL), which pred icts an alteration in lipid fuel partitioning which may then contribut e to resumption of the obese state. The purpose of this study was to t est whether changes in skeletal muscle LPL (SMLPL) and its response to insulin/glucose after sustained weight reduction also indicate a pote ntial 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 f or 3 months followed by 3 months of isocaloric maintenance of the redu ced weight (n=11, 82+/-4 kg). SMLPL activity was measured in the faste d state and after 6 h insulin/glucose infusion, before and after susta ined weight loss. SMLPL activities were also measured in six normal we ight women. Fasting SMLPL activity in obese women (39+/-0.3 nmol FFA m in(-1) g(-1)) was similar to that measured in normal weight control wo men (4.4+/-0.5). Unlike normal weight controls in whom a 6 h insulin/g lucose infusion decreased SMLPL activity, in obese women the response of SMLPL was positive (normal weight vs, obese: Delta-0.8+/-0.3 vs. De lta 1.6+/-0.5, P=0.002). Following maintained weight reduction, fastin g SMLPL in the obese group was reduced to 1.2+/-0.3 (obese before weig ht loss vs. obese after: P=0.0001). This change in fasting SMLPL activ ity following weight loss/maintenance correlated with the resultant ch ange in per cent body fat (r(s)=0.663, P=0.026). Following sustained w eight reduction in the obese women, the change in SMLPL activity in re sponse to insulin/glucose infusion was unchanged by statistical compar ison. However, the trend of the direction of that change was toward a more normal value. Overall, the decrease in SMLPL which occurred follo wing sustained weight loss may explain, in part, why prolonged weight reduction in obese subjects is difficult to maintain.