Relationships in women between body mass index and the intravascular metabolism of chylomicron-like emulsions

Abstract

OBJECTIVE:To investigate whether increasing body mass index (BMI) produces increasingly intense disturbances in the metabolism of chylomicrons, the lipoproteins that carry the dietary lipids absorbed by the intestine in the circulation. SUBJECTS: Four groups of 10 normolipidemic nondiabetic women at the normal (BMIo25 kg/m 2 ), preobese , obese and morbid obese (BMI440). METHODS: Chylomicron metabolism was studied using the method of triglyceride-rich emulsions that mimic chylomicrons. The chylomicron-like emulsion doubly labeled with 3 H-triolein (TO) and 14 C-cholesteryl-oleate (CO) was intravenously injected to calculate the plasma fractional clearance rates (FCR, in min À1 ) by a compartmental analysis model. FCR-TO mirrors both the lipolysis from lipoprotein lipase that the emulsion suffers while still in the circulation, and the triglycerides portion that is not broken down and is removed from the plasma together with the remnant particles. Lipolysis index is calculated subtracting CO from TO areas under the curve. RESULTS: FCR-TO did not differ among the four groups. The lipolysis index was positively correlated with BMI (r ¼ 0.310; P ¼ 0.05). On the other hand, FCR-CO progressively diminished from the normal to the morbid obese group (0.06970.01; 0.06470.01; 0.03170.003; 0.02970.005 min À1 , respectively, P ¼ 0.003) and there was a negative correlation between FCR-CO and BMI (r ¼ À0.388; P ¼ 0.01). CONCLUSION: In obesity, the capacity to break down chylomicron triglycerides by lipoprotein lipase in vivo increases, but the ability of the organism to remove the resulting chylomicron remnants particles progressively diminishes as the BMI rises. Remnant accumulation most likely predisposes to coronary artery disease development. The increased risk of developing coronary artery diseases in obese subjects may be related, among other causes, to disturbances in the plasma lipoproteins elicited by the weight gain. 1,2 Fasting hypertriglyceridemia is the main dyslipidemia found in obesity. It reflects the plasma accumulation of very-low-density lipoprotein (VLDL), the triglyceride-rich lipoprotein produced by the liver. 3 Low plasma HDL cholesterol may also be found in obese subjects due to the seesaw effect, whereby VLDL and HDL plasma concentration are inversely correlated. 4,5 Owing to the action of transfer proteins, the cholesterol net mass transfer from HDL to VLDL occurs when VLDL concentration increases by mass action law, thus decreasing HDL cholesterol. 5 Furthermore, hepatic lipase is increased in obesity 6 and as this enzyme promotes HDL degradation by the liver, the lipoprotein concentration decreases. 7 Hypertriglyceridemia and low HDL are established risk factors for coronary artery disease. The status in obesity of low-density lipoprotein (LDL) cholesterol is less clear: in some studies it was found increased, while in others it was normal. 1,8 On the other hand, small, dense LDL, which is the LDL subfraction considered as more atherogenic, may be enhanced in obesity. 2

Metabolism of a Lipid Nanoemulsion Resembling Low-Density Lipoprotein in Patients with Grade III Obesity

“…This finding suggests that, although the lipolysis process occurs normally in the obese, there is difficulty in removing the remnants from circulation, a defect that is associated with atherosclerosis development. In the correlation study on obese subjects that was subsequently performed, a negative correlation between cholesteryl ester removal (i.e., remnant removal) and BMI was found; in contrast, lipolysis correlated positively with BMI 21. One can hypothesize that the excess insulin in the plasma of obese subjects stimulates lipolysis, whereas their obesity inhibits the mechanisms of remnant removal, in which LDL receptors are also involved.…”