The Microsomal Triglyceride Transfer Protein Inhibitor, Lomitapide, Improves Vascular Function in Obesity

Abstract

ObjectivesIn this study, we investigate the effect of lomitapide, a microsomal triglyceride transfer protein inhibitor, on cardiovascular function in obesity.HypothesisWe hypothesize that lipid level downregulation by lomitapide is a fundamental mechanism that improves cardiovascular function.MethodsEight‐week‐old C57/b6 mice were fed with a high fat diet (HFD) for 12 weeks in the presence and absence of lomitapide. Lomitapide was administered by gavage (1mg/Kg/Day) for the last 2 weeks of HFD feeding. Bodyweight, blood glucose, body composition, and lipid profile were determined. Vascular function and endothelial function markers were studied in aorta and mesenteric resistance arteries (MRA).ResultsLomitapide treatment reduced the body weight in obese mice. Blood glucose, % of fat mass, total cholesterol, and LDL levels were significantly reduced and the % of lean mass was significantly increased after lomitapide treatment. Aortic and mesenteric arteries vascular response to sodium nitroprusside (SNP) was similar among groups. However, the vascular response to acetylcholine (Ach) was improved in the treated group. This was associated with a decreased level of vascular endoplasmic (ER) reticulum stress, inflammation, and oxidative stress.ConclusionsTreatment with lomitapide attenuated the increase in body weight in obese mice and restored the lipid profile and vascular function. These effects were accompanied by a decrease in inflammation and oxidative stress.