orlistat and Arteriosclerosis

More than half of the men and women in the United States are overweight or obese. Obesity is associated with an increased risk for various diseases, most notably, hypertension, diabetes mellitus, dyslipidemia, and coronary heart disease (CHD). The location of excessive body fat, particularly in the visceral area, has the strongest association with these factors that comprise the insulin resistance syndrome. A reduction in as little as 10% of baseline weight has been shown to improve the control of blood pressure and glucose, as well as to reduce triglycerides and increase high-density lipoprotein (HDL) cholesterol. Therefore, obesity should be considered a predisposing CHD risk factor, and treatment with diet, exercise, and newer pharmacologic agents can help patients achieve and maintain desired weight-loss goals.

Topics: Anti-Obesity Agents; Arteriosclerosis; Coronary Disease; Diabetes Complications; Female; Humans; Hyperlipidemias; Hypertension; Insulin Resistance; Lactones; Male; Obesity; Orlistat; Risk Factors; Weight Loss

Orlistat lowers lipids and improves insulin sensitivity, but its effect on other metabolic syndrome related parameters is not known. To assess its influence on adiponectin, high sensitive C-reactive protein (hs-CRP) and other metabolic syndrome related parameters, this study enrolled 106 participants in a weight-reduction program and categorized them into a group of 51 who had been treated with orlistat 360 mg/day for one year and a group of 55 age and sex and body mass index (BMI) matched controls. The orlistat group had greater changes in BMI, % body fat (% BF), waist circumference, and insulin resistance, hs-CRP, leptin and adiponectin levels after one year on the program than the controls. After adjusting for % BF and waist circumference, change of serum leptin and adiponectin levels remained significantly different. It was found that orlistat could effectively manage obesity related co-morbidities, especially insulin resistance and atherosclerosis risk. It decreases leptin and increases adiponectin independent of % BF and waist circumference. Therefore, orlistat appears to have anti-diabetic and anti-atherogenic properties and may help prevent metabolic syndrome in the overweight people.

Topics: Adult; Anti-Obesity Agents; Arteriosclerosis; Blood Glucose; Body Mass Index; C-Reactive Protein; Cholesterol; Diabetes Mellitus; Female; Humans; Hypoglycemic Agents; Lactones; Lipoproteins; Male; Middle Aged; Obesity; Orlistat; Weight Loss

To investigate whether gastrointestinal lipase inhibition reduces the progression of a western-type diet induced atherosclerosis, male apolipoprotein-E knockout (apoE KO) mice were administered orlistat ((S)-1-[[(S, 2S, 3S)-3-hexyl-4-oxo-2-oxetanyl] methyl]dodecyl-(S)-2-formamido-4-methylvalerate) mixed with a western-type diet for 8 weeks. Orlistat significantly reduced plasma triglyceride levels, but not total cholesterol levels, at 4 and 8 weeks of treatment. Increase in plasma triglyceride levels after oral olive oil loading in the mice fed a western-type diet was significantly suppressed in the orlistat treated group at 4 weeks of treatment. After 8 weeks treatment, atherosclerotic lesion area in the aorta of the orlistat treated group was significantly smaller than that of the control group. These results suggest that gastrointestinal lipase inhibition reduces the progression of atherosclerosis through a triglyceride-lowering effect, via inhibition of fat absorption.

Topics: Animals; Apolipoproteins E; Arteriosclerosis; Cholesterol, Dietary; Diet, Atherogenic; Gastrointestinal Tract; Lactones; Lipase; Male; Mice; Mice, Knockout; Orlistat; Triglycerides