Membrane-bound O-acyltransferase 7 (MBOAT7)-driven phosphatidylinositol remodeling in advanced liver disease

Varadharajan, Venkateshwari; Massey, William; Brown, J. Mark

doi:10.1016/j.jlr.2022.100234

Cited by 19 publications

(13 citation statements)

References 103 publications

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“…decreased concentrations of PI (36:4), PI (38:3), PI (38:5)), consistent with decreased MBOAT7 function. 10 These lipids play a critical role in the regulation of membrane dynamics and signal transduction, [41][42][43] possibly also affecting the pathways needed for signal transduction, membrane shape and fusion events such as endocytosis, cytokinesis and vesicle trafficking. 42 In the present study, the liver dysfunction detected in NAFLD patients seems to be independent of the grade of fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Effects of MBOAT7 polymorphism and steatosis on liver function assessed by methacetin breath test

Ciaula

Bonfrate

Shanmugam

et al. 2023

Eur J Clin Investigation

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Background: MBOAT7 rs641738 variant is a risk factor for nonalcoholic fatty liver disease (NAFLD) and liver fibrosis, but the relationship between this polymorphism and early liver dysfunction remains uncertain.Methods: Eighty outpatients underwent blood analyses, liver imaging by ultrasound and acoustic radiation force impulse shear wave elastography and were genotyped for MBOAT7 (wild-type [WT], rs641738 heterozygous or homozygous) polymorphism using TaqMan assays.Results: NAFLD was confirmed in 53 patients. Portal uptake and hepatocyte microsomal metabolization of ( 13 C

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Section: Discussionmentioning

confidence: 99%

Effects of MBOAT7 polymorphism and steatosis on liver function assessed by methacetin breath test

Ciaula

Bonfrate

Shanmugam

et al. 2023

Eur J Clin Investigation

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“…MBOAT7 functions to remodel phosphatidyl inositol with arachidonic acid and is primarily expressed in the liver ( 13 – 15 ). The rs641738 mutation (C > T), increases the risk of developing not only MAFLD, but an entire spectrum of liver diseases (NASH, cirrhosis, and hepatocellular carcinoma) ( 16 , 17 ). The TM6SF2 protein facilities hepatic secretion of triglyceride-rich lipoproteins through the VLDL secretion pathway.…”

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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“…Genetic association studies have highlighted that some of the genetic factors which influence the individual's susceptibility to SLD are strongly associated with lipid droplet biogenesis and turnover (Table 1) [29,34,36,[39][40][41][42][43]. Specifically, certain genetic variants encoding lipid droplet proteins have been identified as instrumental in the onset and progression of SLD.…”

Section: Genetic Factors Associated With Lipid Droplets and Steatotic...mentioning

confidence: 99%

Lipid droplets in steatotic liver disease

Bilson,

Scorletti

2023

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

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Purpose of review This review aims to discuss the most recent evidence exploring the role of lipid droplets in steatotic liver disease (SLD). We highlight the breadth of mechanisms by which lipid droplets may contribute to the progression of SLD with a particular focus on the role of lipid droplets as inducers of mechanical stress within hepatocytes and genetic mutations in lipid droplet associated proteins. Finally, this review provides an update on clinical trials exploring the therapeutic potential and strategies targeting lipid droplets. Recent findings The size, composition and location of hepatic lipid droplets strongly influence the pathological role of these organelles in SLD. Emerging studies are beginning to elucidate the importance of lipid droplet induced hepatocyte mechanical stress. Novel strategies targeting lipid droplets, including the effects of lipid droplet associated protein mutations, show promising therapeutic potential. Summary Much more than a histological feature, lipid droplets are complex heterogenous organelles crucial to cellular metabolism with important causative roles in the development and progression of SLD. Lipid droplet induced mechanical stress may exacerbate hepatic inflammation and fibrogenesis and potentially contribute to the development of a pro-carcinogenic hepatic environment. The integration of advancements in genetics and molecular biology in upcoming treatments aspires to transcend symptomatic alleviation and address the fundamental causes and pathological development of SLD.

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Membrane-bound O-acyltransferase 7 (MBOAT7)-driven phosphatidylinositol remodeling in advanced liver disease

Cited by 19 publications

References 103 publications

Effects of MBOAT7 polymorphism and steatosis on liver function assessed by methacetin breath test

Effects of MBOAT7 polymorphism and steatosis on liver function assessed by methacetin breath test

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

Lipid droplets in steatotic liver disease

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