The Effect of Orlistat on Sterol Metabolism in Obese Patients

Abstract

BackgroundOrlistat, a reversible inhibitor of pancreatic and gastric lipase, is known to have anti-obesity and antioxidant properties. Cholesterol intermediates and metabolites have diverse and important functions in cardiovascular disease. Therefore, we aimed to evaluate the effect of orlistat on sterol metabolism in overweight and obese adults after weight loss during the intervention or weight loss at 12 weeks.MethodsA total of 51 (27 in the control group and 24 in the experimental group), patients with a BMI of 27 or greater were randomly assigned in a 1:1 ratio to receive either orlistat (120 mg) three times a day plus phentermine hydrochloride (37.5 mg) once daily or a placebo three times a day plus phentermine hydrochloride (37.5 mg) once daily. The primary study outcome was sterol metabolism.ResultsThe experimental group exhibited significantly decreased metabolic signatures of serum sterols, free cholesterol, sitosterol, 7α-hydroxycholesterol (7α-OHC), and 7β-OHC at 12 weeks. The experimental group also exhibited significantly decreased metabolic ratios of sitosterol and 7α-OHC to cholesterol at 12 weeks. Regarding changes in sterol signatures from baseline to 6-month follow-up, free cholesterol, plant sterols, and cholesterol precursors tended to decrease with weight loss during the intervention and increase again as the weight was regained in both groups.ConclusionOrlistat treatment improves oxysterol metabolism in overweight and obese adults. Our findings support that orlistat plays a crucial role in the process of endothelial dysfunction and atherosclerosis via oxysterol modulation.

FDA-Approved Pharmacotherapy for Weight Loss Over the Last Decade

“…There are currently five FDA-approved medications for the management of obesity [10][11][12]. A sixth drug, lorcaserin, was approved for weight loss but was later withdrawn, after being in clinical use for eight years, due to concerns of increased risk of cancer [11].…”

“…Orlistat is a pancreatic lipase and gastric lipase inhibitor that can lead to a decrease in fat absorption by as much as 30% contributing to weight loss [12,13]. Yu et al found that administration of orlistat in combination with diet or diet and exercise versus diet alone led to a reduction in body mass index, body weight, waist circumference, and levels of total cholesterol and low-density lipoprotein (LDL) cholesterol [14].…”

Pharmacotherapy of obesity: an update on the available medications and drugs under investigation

“…The primary outcome was sterol metabolism, which was assessed by measuring the change in the serum levels of sterols from baseline to 12 weeks, and weight was one of the secondary outcomes. 90 At 12 weeks, the drop in weight was 8.6 (0.8) kg with phentermine and orlistat, compared to 6.9 (0.6) kg with phentermine and placebo (p 0.04). Adverse events were not reported.…”

Molecular Docking of Citrus amblycarpa Active Compounds against FTO, Leptin, and Resistin Protein

“…Therefore, hesperidin and naringin in C. amblycarpa peel may have a potential to reduce plasma lipids, and play an important role as antioxidants. 22 Orlistat inhibits fat absorption from triglyceride hydrolysis by inhibiting lipase 24 , which reduces and…”