The microsomal triglyceride transfer protein inhibitor lomitapide improves vascular function in mice with obesity

Munkhsaikhan, Undral; Kwon, Young‐In; Sahyoun, Amal M.; Ait‐Aissa, Karima; Kassan, Adam; Kassan, Modar

doi:10.1002/oby.23389

Cited by 4 publications

(1 citation statement)

References 38 publications

(47 reference statements)

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“…Xie et al also found that Mtp iKO mice fed a high-fat-fructose-cholesterol diet for 10 weeks exhibited a sustained reduction in hepatic TG ( Xie et al, 2021 ). MTP inhibitor lomitapide, has also shown beneficial effects in improving obesity, blood glucose, lipids, and blood vessels ( Hooper et al, 2015 ; Munkhsaikhan et al, 2022 ). Lomitapide, however, targets both intestinal and hepatic MTP.…”

Section: Effects Of the Genes Involved In Regulating Dietary Triglyce...mentioning

confidence: 99%

New insights into the role of dietary triglyceride absorption in obesity and metabolic diseases

Liu²,

Pan³

et al. 2023

Front. Pharmacol.

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The incidence of obesity and associated metabolic diseases is increasing globally, adversely affecting human health. Dietary fats, especially triglycerides, are an important source of energy for the body, and the intestine absorbs lipids through a series of orderly and complex steps. A long-term high-fat diet leads to intestinal dysfunction, inducing obesity and metabolic disorders. Therefore, regulating dietary triglycerides absorption is a promising therapeutic strategy. In this review, we will discuss diverse aspects of the dietary triglycerides hydrolysis, fatty acid uptake, triglycerides resynthesis, chylomicron assembly, trafficking, and secretion processes in intestinal epithelial cells, as well as potential targets in this process that may influence dietary fat-induced obesity and metabolic diseases. We also mention the possible shortcomings and deficiencies in modulating dietary lipid absorption targets to provide a better understanding of their administrability as drugs in obesity and related metabolic disorders.

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Section: Effects Of the Genes Involved In Regulating Dietary Triglyce...mentioning

confidence: 99%

New insights into the role of dietary triglyceride absorption in obesity and metabolic diseases

Liu²,

Pan³

et al. 2023

Front. Pharmacol.

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Lomitapide: navigating cardiovascular challenges with innovative therapies

Munkhsaikhan,

Ait-Aissa,

Sahyoun

et al. 2024

Mol Biol Rep

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The Beneficial Effect of Lomitapide on the Cardiovascular System in LDLr−/− Mice with Obesity

et al. 2023

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Objectives: Homozygous familial hypercholesteremia (HoFH) is a rare, life-threatening metabolic disease, mainly caused by a mutation in the LDL receptor. If untreated, HoFH causes premature death from acute coronary syndrome. Lomitapide is approved by the FDA as a therapy to lower lipid levels in adult patients with HoFH. Nevertheless, the beneficial effect of lomitapide in HoFH models remains to be defined. In this study, we investigated the effect of lomitapide on cardiovascular function using LDL receptor-knockout mice (LDLr−/−). Methods: Six-week-old LDLr−/− mice were fed a standard diet (SD) or a high-fat diet (HFD) for 12 weeks. Lomitapide (1 mg/Kg/Day) was given by oral gavage for the last 2 weeks in the HFD group. Body weight and composition, lipid profile, blood glucose, and atherosclerotic plaques were measured. Vascular reactivity and markers for endothelial function were determined in conductance arteries (thoracic aorta) and resistance arteries (mesenteric resistance arteries (MRA)). Cytokine levels were measured by using the Mesoscale discovery V-Plex assays. Results: Body weight (47.5 ± 1.5 vs. 40.3 ± 1.8 g), % of fat mass (41.6 ± 1.9% vs. 31.8 ± 1.7%), blood glucose (215.5 ± 21.9 vs. 142.3 ± 7.7 mg/dL), and lipid levels (cholesterol: 600.9 ± 23.6 vs. 451.7 ± 33.4 mg/dL; LDL/VLDL: 250.6 ± 28.9 vs. 161.1 ± 12.24 mg/dL; TG: 299.5 ± 24.1 vs. 194.1 ± 28.1 mg/dL) were significantly decreased, and the % of lean mass (56.5 ± 1.8% vs. 65.2 ± 2.1%) was significantly increased in the HFD group after lomitapide treatment. The atherosclerotic plaque area also decreased in the thoracic aorta (7.9 ± 0.5% vs. 5.7 ± 0.1%). After treatment with lomitapide, the endothelium function of the thoracic aorta (47.7 ± 6.3% vs. 80.7 ± 3.1%) and mesenteric resistance artery (66.4 ± 4.3% vs. 79.5 ± 4.6%) was improved in the group of LDLr−/− mice on HFD. This was correlated with diminished vascular endoplasmic (ER) reticulum stress, oxidative stress, and inflammation. Conclusions: Treatment with lomitapide improves cardiovascular function and lipid profile and reduces body weight and inflammatory markers in LDLr−/− mice on HFD.

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The microsomal triglyceride transfer protein inhibitor lomitapide improves vascular function in mice with obesity

Cited by 4 publications

References 38 publications

New insights into the role of dietary triglyceride absorption in obesity and metabolic diseases

New insights into the role of dietary triglyceride absorption in obesity and metabolic diseases

Lomitapide: navigating cardiovascular challenges with innovative therapies

The Beneficial Effect of Lomitapide on the Cardiovascular System in LDLr−/− Mice with Obesity

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