Effect of weight reduction on the distribution of apolipoprotein A-I in high-density lipoprotein subfractions in obese non-insulin-dependent diabeticsubjects

High-density lipoprotein (HDL) plays an important role in the process of re verse cholesterol transport, which may become suboptimal with increasing bo dy fatness. HDL cholesterol that is reduced in obese subjects paradoxically decreases during weight reduction. To determine how weight reduction affec ts HDL subclasses that are involved in reverse cholesterol transport, we st udied HDL from obese diabetic subjects before and after energy restriction within background diets high in either carbohydrate or monounsaturated fatt y acids (MUFAs), Body weight, blood glucose, total cholesterol, and LDL cho lesterol decreased after 8 and 12 weeks of weight reduction. With the very- low-fat diet, HDL cholesterol decreased significantly at 8 weeks, but recov ered to initial levels after 12 weeks as body weight began to stabilize. Pl asma apolipoprotein A-I (apo A-I) decreased substantially and significantly at 8 and 12 weeks with both diets, and was reflected in the reduction of a po A-I in HDL subclasses alpha (1), alpha (2), pre-beta (1), and pre-beta ( 2) + pre-beta (3). The calculation of the percentage distribution of apo A- I among HDL species showed that only the proportion of pre-beta (1)-HDL dec reased, whereas alpha (2)-HDL increased. This led to a significant increase in the alpha (1) + alpha (2)/pre-beta ratio, ie, the ratio of the large ch olesterol "storage" or "sink" HDL to the HDL "shuttle" fraction considered to be the initial acceptor of cell cholesterol. These data suggest that des pite the reduction in HDL cholesterol and apo A-I, the redistribution of ap o A-I in pre-beta (1)-HDL and alpha -HDL observed with weight reduction app ears to revert to the pattern that we have previously reported in lean as o pposed to overweight subjects. Copyright (C) 2000 by W.B. Saunders Company.