Postprandial dyslipidemia in men with visceral obesity: an effect of reduced LDL receptor expression?

Postprandial lipemia after an oral fat challenge was studied in middle-aged men with visceral obesity. The two groups had similar plasma cholesterol l evels, but obese subjects had higher levels of plasma triglyceride and redu ced amounts of high-density cholesterol. Fasting plasma insulin was fourfol d greater in obese subjects because of concomitant insulin resistance, with a calculated HOMA score of 3.1 +/- 0.6 vs. 0.8 +/- 0.2, respectively. Plas ma apolipoprotein B-48 (apoB(48)) and retinyl palmitate (RP) after an oral fat challenge were used to monitor chylomicron metabolism. Compared with le an subjects, the fasting concentration of apoB48 was more than twofold grea ter in obese individuals, suggestive of an accumulation of posthydrolyzed p articles. After the oral lipid load, the incremental areas under the apoB(4 8) and RP curves (IAUC) were both significantly greater in obese subjects ( apoB48: 97 +/- 17 vs. 44 +/- 12 mug.ml(-1).h; RP: 3,120 +/- 511 vs. 1,308 /- 177 U.ml(-1).h, respectively). A delay in the conversion of chylomicrons to remnants probably contributed to postprandial dyslipidemia in viscerall y obese subjects. The triglyceride IAUC was 68% greater in obese subjects ( 4.7 +/- 0.6 vs. 2.8 +/- 0.8 mM.h, P < 0.06). Moreover, peak postprandial tr iglyceride was delayed by <similar to>2 h in obese subjects. The reduction in triglyceride lipolysis in vivo did not appear to reflect changes in hydr olytic enzyme activities. Postheparin plasma lipase rates were found to be similar for lean and obese subjects. In this study, low-density lipoprotein (LDL) receptor expression on mononuclear cells was used as a surrogate mar ker of hepatic activity. We found that, in obese subjects, the binding of L DL was reduced by one-half compared with lean controls (70.9 +/- 15.07 vs. 38.9 +/- 4.6 ng LDL bound/mug cell protein, P = 0.02). Because the LDL rece ptor is involved in the removal of proatherogenic chylomicron remnants, we suggest that the hepatic clearance of these particles might be compromised in insulin-resistant obese subjects. Premature and accelerated atherogenesi s in viscerally obese, insulin-resistant subjects may in part reflect delay ed clearance of postprandial lipoprotein remnants.