Session: 723 APS Cardiovascular and renal mechanisms in diabetes and metabolic syndrome Poster Session
(723.1) The Microsomal Triglyceride Transfer Protein Inhibitor, Lomitapide, Improves Vascular Function in Obesity
Monday, April 4, 2022
10:15 AM – 12:15 PM
Location: Exhibit/Poster Hall A-B - Pennsylvania Convention Center
Poster Board Number: E168
Undral Munkhsaikhan (University of Tennessee Health Science Center), Young-In Kwon (University of Tennessee Health Science Center), Amal Sahyoun (University of Tennessee Health Science Center, University of Tennessee Health Science Center), Karima Ait-Aissa (Cardiovascular Division, Department of Medicine and Abboud Cardiovascular Research Center, University of Iowa Carver College of Medicine), Modar Kassan (University of Tennessee Health Science Center), Adam Kassan (School of Pharmacy, West Coast University)
Presenting Author University of Tennessee Health Science Center
Objectives: In this study, we investigate the effect of lomitapide, a microsomal triglyceride transfer protein inhibitor, on cardiovascular function in obesity.
Hypothesis: We hypothesize that lipid level downregulation by lomitapide is a fundamental mechanism that improves cardiovascular function.
Methods: Eight-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).
Results: Lomitapide 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.
Conclusions: Treatment 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.
