Weight loss in massive obesity: Reciprocal changes in plasma HDL cholesterol and HDL binding to human adipocyte plasma membranes

Abstract

Human obesity is frequently associated with elevated plasma triglyceride and cholesterol concentrations and reduced high density lipoprotein (HDL) cholesterol, abnormalities that commonly revert to normal levels with weight loss. This study was undertaken to examine possible mechanism(s) associated with the changes in plasma HDL cholesterol concentrations in massively obese patients after weight loss. Ten massively obese patients (two men and eight women, age = 37.8 ± 2.4 years) were studied before, during, and after 1 year of weight loss and weight maintenance following gastric stapling. Total cholesterol and low density lipoprotein cholesterol were within the normal range for sex and age before weight loss and did not change significantly during or after weight reduction. In the females, HDL cholesterol concentrations increased from 0.96 ± 0.06 mmol/L to 1.23 ± 0.3 mmol/L (mean ± SEM, n = 8, P < .05) with weight reduction. In the two men, plasma HDL cholesterol concentrations were, respectively, 1.22 and 0.65 mmol/L before and 1.23 and 0.98 mmol/L after weight loss. Specific binding of 125I-HDL 2 and 125I-HDL 3 to purified plasma membranes was determined using abdominal and omental fat depot before and after weight loss in six of the ten obese patients. An average reduction of 30% to 40% in 125I-HDL 2 and 125I-HDL 3 binding capacity to these membranes occurred after weight loss. Furthermore, a positive correlation ( r = .65, n = 10, P < .05) was observed between plasma HDL cholesterol and triglyceride concentrations before weight loss but not after weight loss ( r = .01). The changes in plasma HDL cholesterol and plasma triglyceride concentrations following weight loss were also not significantly related ( r = .55, n = 10). However the change in plasma HDL cholesterol correlated significantly with the change in HDL 2 binding to abdominal subcutaneous adipocyte plasma membranes ( r = 0.97, n = 5, P < .01). These results show that reduced plasma HDL cholesterol in obesity is not necessarily associated with hypertriglyceridemia. The increase in HDL cholesterol with weight loss and weight maintenance was gradual and delayed and is therefore not simply the result of acute nutritional adjustments. The reciprocal changes in HDL binding to adipocyte membranes suggest that fat tissue may participate directly in modifying plasma HDL cholesterol in obesity.