Does plasma HDL-C concentration interact with whole-body cholesterol metabolism?

This review examines the interactions between plasma high density lipoprotein (HDL) metabolism and whole-body cholesterol economy. More specifically, this review addresses three questions: 1) does plasma HDL-C concentration correlate with the parameters of whole-body cholesterol metabolism? 2) Do variations in cholesterol metabolism interfere with plasma HDL-C concentrations? 3) Are the markers of cholesterol synthesis and intestinal absorption specifically under the control of plasma HDL? The following answers were provided to each question, respectively: 1) plasma HDL influences whole-body cholesterol synthesis rate but the evidence that HDL modifies the total amount of cholesterol absorbed by the intestine is not clearly supported by present investigations; 2) there are suggestions that changes in whole body cholesterol metabolism rates do not interfere with plasma HDL-C concentrations; 3) markers of cholesterol synthesis and absorption may specifically be controlled by plasma HDL-C concentrations regarding the genetic causes of extremely low HDL-C concentrations, although within the general population plasma HDL-C concentration is likely ascribed to insulin resistance or diabetes mellitus.

HDL-C concentration is related to markers of absorption and of cholesterol synthesis: Study in subjects with low vs. high HDL-C.

BACKGROUND: The antiatherogenic functions of high density lipoprotein (HDL-C) include its role in reverse cholesterol transport, but to what extent the concentration of HDL-C interferes with the whole-body cholesterol metabolism is unknown. Therefore, we measured markers of body cholesterol synthesis (desmosterol and lathosterol) and of intestinal cholesterol absorption (campesterol and ß-sitosterol) in healthy subjects that differ according to their plasma HDL-C concentrations. METHODS: Healthy participants presented either low HDL-C (< 40 mg/dl, n=33, 17 male and 16 female) or high HDL-C (> 60 mg/dl, n=33, 17 male and 16 female), BMI< 30 kg/m², were paired according to age and gender, without secondary factors that might interfere with their plasma lipid concentrations. Plasma concentrations of non-cholesterol sterols were measured by the combined GC-MS analysis. RESULTS: Plasma desmosterol did not differ between the two groups; however, as compared with the high HDL-C participants, the low HDL-C participants presented higher concentration of lathosterol and lower concentration of the intestinal cholesterol absorption markers campesterol and ß-sitosterol. CONCLUSION: Plasma concentrations of HDL, and not the activities of LCAT and CETP that regulate the reverse cholesterol transport system, correlate with plasma sterol markers of intestinal cholesterol absorption directly, and of cholesterol synthesis reciprocally.

A randomized double-blind placebo-controlled study of the long-term efficacy and safety of diethylpropion in the treatment of obese subjects.

OBJECTIVE: To evaluate the efficacy of diethylpropion on a long-term basis, with emphasis in cardiovascular and psychiatric safety aspects. DESIGN: Randomized, double-blind, placebo-controlled trial. MEASUREMENTS: Following a 2-week screening period, 69 obese healthy adults received a hypocaloric diet and were randomized to diethylpropion 50 mg BID (n=37) or placebo (n=32) for 6 months. After this period, all participants received diethylpropion in an open-label extension for an additional 6 months. The primary outcome was percentage change in body weight. Electrocardiogram (ECG), echocardiography and clinical chemistry were performed at baseline and every 6 months. Psychiatric evaluation and application of Hamilton rating scales for depression and anxiety were also performed by experienced psychiatrists at baseline and every 3 months. RESULTS: After 6 months, the diethylpropion group lost an average of 9.8% (s.d. 6.9%) of initial body weight vs 3.2% (3.7%) in the placebo group (P<0.0001). From baseline to month 12, the mean weight loss produced by diethylpropion was 10.6% (8.3%). Participants in the placebo group who were switched to diethylpropion after 6 months lost an average of 7.0% (7.7%) of initial body weight. The difference between groups at month 12 was not significant (P=0.07). No differences in blood pressure, pulse rate, ECG and psychiatric evaluation were observed. Dry mouth and insomnia were the most frequent adverse events. CONCLUSION: Diethylpropion plus diet produced sustained and clinically significant weight loss over 1 year. It seems to be safe in relation to cardiovascular and psychiatric aspects in a well-selected population.