Postprandial effect of Orlistat on the peaking of lipid level after sequential high fat meals

ABSTRACT

Postprandial lipemia has been found to be strongly associated with atherosclerosis due to its atherogenic and thrombogenic lipoprotein changes. This phenomenon occurs even in normal subjects especially after high fat meals. Orlistat, an anti- obesity drug, has been shown to address postprandial lipemia after a single high fat meal. To compare the effects of orlistat and placebo on the postprandial lipid levels after sequential high-fat meals in healthy individuals with normal fasting lipid levels. Thirty-one healthy adult volunteers with normal fasting lipid levels were fed 50% fat meals [3 meals and 2 snacks of pre-weighted butter and bread]. The subjects were blindly randomized to receive either placebo or orlistat 120 mg before each main meal. The outcome parameters were total cholesterol [TC], triglyceride [TG], high-density lipoprotein [HDL] cholesterol, low-density lipoprotein [LDL] cholesterol, and very-low-density lipoprotein [VLDL] cholesterol levels measured at fasting [0 h] and every 2 h thereafter, until the sixteenth hour. Additionally, we estimated the lipid levels at the fifth and ninth hour. The non-orlistat group showed a significant postprandial rise in the levels of TG and VLDL, which began 4 h after breakfast [P < 0.05]; this rise in levels was sustained until 9 h after breakfast for TG and up to 10 h after breakfast for VLDL. In contrast, only one significant rise in both TG and VLDL levels [at 4 h after breakfast] was noted in the orlistat group. The maximum mean difference from the baseline TG level for the orlistat group was lower than that for the non-orlistat group [0.22 mmol/L vs. 0.756 mmol/L, respectively]. Similarly, the maximum mean difference from the baseline VLDL level from baseline in the orlistat group was only 0.099 mmol/L, which was lower than that in the non-orlistat group [0.588 mmol/L]. LDL levels rose to a lesser extent in the orlistat group than in the non-orlistat group [0.268 vs. 0.362 mmol/L]. The TC levels did not show a postprandial rise; instead, the levels reduced in both groups, with the orlistat group showing a higher reduction than the non-orlistat group [-0.288 vs. -0.188 mmol/L]. The orlistat group did not show any significant differences in the HDL measurements. Administration of orlistat abolished the significantly sustained postprandial rise of TG and VLDL levels in healthy individuals who were fed sequential 50% fat meals