Elevated Serum Low-Density Lipoproteins-Cholesterol Levels and B1B2/B2B2 <i>CETP</i> Genotype Are Positively Associated with Nonalcoholic Fatty Liver Disease in Women with Gallstone Disease

Perez-Robles, Mariana; Campos-Pérez, Wendy; Rivera-Valdés, Juan José; Franco-Topete, Ramón Antonio; Navarrete-Medina, Eduardo Miguel; Maldonado-González, Montserrat; Ruíz-Madrigal, Bertha; Rodríguez-Reyes, Sarai Citlalic; Martínez‐López, Erika

doi:10.1089/met.2022.0010

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Pathophysiological Processes In the Development Of Mafld1

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2023

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“…Because of this, MAFLD patients often present with pro-atherogenic lipid profiles (e.g., low HDL-C and elevated LDL-C, TG, and apolipoprotein B) ( 11 , 19 , 22 , 24 ). Humans have a compensatory mechanism to reduce hepatic fat content through the activity of cholesterol ester transfer protein (CETP), which exchanges TG and cholesterol esters between VLDL, HDL, and LDL cholesterol ( 25 – 27 ). However, this mechanism often results in abnormally high HDL cholesterol metabolism and leads to undesirable alterations in lipid profiles in patients.…”

Section: Pathophysiological Processes In the Development Of Mafldmentioning

confidence: 99%

Development of LXR inverse agonists to treat MAFLD, NASH, and other metabolic diseases

Griffett

Burris

2023

Front. Med.

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Activation of LXR activity by synthetic agonists has been the focus of many drug discovery efforts with a focus on treatment of dyslipidemia and atherosclerosis. Many agonists have been developed, but all have been hindered due to their ability to efficaciously stimulate de novo lipogenesis. Here, we review the development of LXR inverse agonists that were originally optimized for their ability to enable recruitment of corepressors leading to silencing of genes that drive de novo lipogenesis. Such compounds have efficacy in animal models of MAFLD, dyslipidemia, and cancer. Several classes of LXR inverse agonists have been identified and one is now in clinical trials for treatment of severe dyslipidemia.

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